Skip to main content
  • Study protocol
  • Open access
  • Published:

Footwear and insole design parameters to prevent occurrence and recurrence of neuropathic plantar forefoot ulcers in patients with diabetes: a series of N-of-1 trial study protocol



Foot complications occur in conjunction with poorly controlled diabetes. Plantar forefoot ulceration contributes to partial amputation in unstable diabetics, and the risk increases with concomitant neuropathy. Reducing peak plantar forefoot pressure reduces ulcer occurrence and recurrence. Footwear and insoles are used to offload the neuropathic foot, but the success of offloading is dependent on patient adherence. This study aims to determine which design and modification features of footwear and insoles improve forefoot plantar pressure offloading and adherence in people with diabetes and neuropathy.


This study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants’ self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis.


This is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants’ preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000699965p. Registered on June 23, 2020

Peer Review reports

Administrative information


Footwear and insole design parameters to prevent occurrence and recurrence of neuropathic plantar forefoot ulcers in patients with diabetes; - A series of N-of-1 trials.

Trial registration

This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), and the registration number is ACTRN12620000699965p. Date: June 23, 2020

Protocol version

December 2021, Version 1.9


As the footwear and insoles are part of the standard treatment for each participant, the funding will be provided by the funding source to which each participant has access. This includes HealthShare Enable NSW [1], private health funds, aged care packages, Closing the Gap or self-funded by participants based on their eligibility criteria. Foot Balance Technology (owned by the chief investigator) will provide support for the F-scan and MatScan systems and relevant sensors. There will be no cost to participants for the sensors.

Author Details

Sayed Ahmed1

Dr Paul Butterworth1

Dr Alex Barwick1

Dr Anita Sharma2,3

Dr Md Zobaer Hasan4,5

Professor Susan Nancarrow1

1School of Health and Human Sciences, Southern Cross University, Queensland, 4225, Australia

2Department of Geriatric Medicine, Nepean Hospital, Penrith, New South Wales, Australia

3Nepean Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia

4School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia

5General Educational Development, Daffodil International University, Daffodil Smart City, Ashulia, Dhaka, Bangladesh.

Name and contact information for the trial sponsor

Sayed Ahmed, Director, Foot Balance Technology Pty Ltd


Role of sponsor

Foot Balance Technology will support the F-scan and MatScan system (including hardware and software) and relevant sensors. There will be no cost to participants for the sensors.


Foot ulcers are a common consequence of diabetes due to the development of peripheral neuropathy, peripheral vascular disease, limited joint mobility and foot deformity [2,3,4,5,6,7]. Nearly 34% of people with diabetes will develop a foot ulcer in their lifetime [8]. This can lead to infection and amputation; diabetes is the main reason for non-traumatic amputation [9, 10]. Previous foot ulceration or amputation is a risk for future amputation [2, 4, 6, 11]. Additional risk factors include a higher body mass index (BMI) and structural foot deformities [3,4,5, 7], such as hammertoes and hallux valgus [12, 13].

Diabetic peripheral neuropathy (DPN) is a risk factor for the development of ulceration [14]. Over 30% of persons with diabetes will develop DPN [15], the incidence increasing with age [16, 17]. DPN can affect the autonomic, sensory and motor nervous systems. Sensory neuropathy interrupts the protective feedback mechanism of touch and pain [18]. Motor neuropathy results in compromised muscle innervation, reduction in strength and, combined with limited joint mobility, the development of foot deformities. These deformities may lead to an increase in plantar foot pressures, particularly in the forefoot [19,20,21,22]. Autonomic neuropathy leads to diminished sweating and changes to skin perfusion, leading to dry skin and hyperkeratosis. As skin integrity is compromised, patients are more susceptible to trauma which may predispose a diabetic foot ulcer [22,23,24,25].

Neuropathic foot ulcers in persons with diabetes occur mostly at the plantar forefoot [12, 26, 27] and correspond to areas of peak plantar pressure (PPP) [28]. Bennetts et al. [29] demonstrated that most peak pressure areas are located in the forefoot regions in this population. A limited range of motion at the forefoot joints is also likely to contribute to the increased PPP observed in this region [30]. For this reason, plantar pressure mapping is used to guide footwear and insole manufacture and judge their effectiveness [31].

Reducing plantar pressures is considered a key factor for wound healing and the prevention of ulcer recurrence [32, 33]. Footwear and insoles are important treatment modalities for offloading these pressures [34, 35]. The desired offloading threshold should be <200 kPa to ensure ulcer-free survival at the forefoot [36]. Some studies also recommended that a pressure relief of 25–30% compared with the baseline be effective [31, 37]. The evidence for effective design characteristics of footwear and insole that can reduce plantar pressure is limited in the literature [38], and further exploration of the various design and modifications of footwear and insole can bridge the gap in the literature [39, 40].

The rationale for performing the study

There is no existing, evidence-based recommendation for overall footwear and insole design that includes all technical specifications to offload the diabetes-related and neuropathic foot [38,39,40]. Several studies have suggested components of footwear design, such as the rocker sole profile, as the preferred design feature to offload PPP at the forefoot [31, 41,42,43,44,45]. Arts et al. [46] in the Netherlands and Rizzo et al. [43] in Italy conducted studies to test the effect of footwear design suggested by the consensus-based algorithm proposed by Dahmen et al. [47]. Both studies found that the footwear and insole design is effective in offloading the neuropathic diabetic foot. However, Arts and colleagues [46] found that the algorithm is not as effective for footwear specifications when offloading plantar pressure at the metatarsal heads is required.

Several studies [31, 43, 45, 48,49,50] have explored patient satisfaction and adherence to wearing footwear and insoles. Patient adherence to wearing therapeutic footwear is important to ensure improved offloading and ulcer prevention [43, 45, 48].

Research aim

The aim of this study is to identify clinically relevant footwear and insole design and modification parameters that effectively offload forefoot PPP in the neuropathic feet of people with diabetes and increase adherence.


The research questions are:

  1. a.

    What factors and parameters need to be considered when prescribing footwear and insoles for people at risk of neuropathic forefoot plantar ulcer occurrence and recurrence?

  2. b.

    How can participants’ preferences be incorporated into footwear and insole design to increase the adherence to prescribed footwear in people with diabetes and neuropathy who are at risk of plantar forefoot ulcer occurrence and recurrence?

Expected outcomes

The overall goal of this intervention is the prevention of ulceration; however, ulceration is an undesirable outcome for participants, so a proxy measure, which is a reduction of plantar pressure using footwear, is used as the primary outcome measure instead.

The expected outcome of the study is an algorithm or best practice recommendations that can be personalised to prescribe footwear and insole design and modifications based on individual pathologies, comorbidities and lifestyles in people with diabetes and peripheral neuropathy who are at risk of plantar forefoot ulceration. This algorithm or best practice recommendation is expected to provide a clear guideline for referrers, patients, prescribers and technicians to design or modify footwear and insole to ensure adequate and effective offloading of the forefoot to prevent the occurrence and recurrence of plantar neuropathic ulcers in people with diabetes.

The recommendations are expected to influence better optimise health service models and health fund’s resource allocation to maximise the impacts.


Trial design

The trial design is shown in the flowchart (Fig. 1).

Fig. 1
figure 1

Trial design flow for the N-of-1 trial

Methodological approach

The study will be comprised of a single patient or N-of-1 trial.

N-of-1 trials are usually randomised, often double-blind, and involve multiple crossover comparisons of an intervention and a control treatment [51, 52]. Oxford Centre for Evidence-Based Medicine has recommended this trial as level 1 evidence for treatment decisions [53].

N-of-1 trials provide a technique to guide evidence-based treatment decisions for an individual patient. They use common methodological components of large clinical trials to measure treatment effectiveness in a single patient. They are a practical alternative when circumstances do not allow for large-scale trials, such as rare diseases or comorbid conditions, or when participants use concurrent therapies [54]. However, the findings from these trials can be used to inform the development of algorithms to guide complex treatments for other patients. In this case, the complexity of the intervention (footwear and insole design) and the individually tailored nature of the intervention lend itself to an N-of-1 trial. This is also a more cost-effective approach than traditional phase three clinical trials [55].

Methodologically robust N-of-1 trials objectively assess the effectiveness of treatments within individual participants. Aggregation of multiple cycles identically conducted N-of-1 trials yields a population estimate of effect, which approximates the similar effect derived from other RCT designs. Trial participants contribute data for both intervention and control treatments creating matched data sets while using generally smaller sample sizes than conventional RCTs [51].

Single-patient or N-of-1 trials are commonly used for personalising the treatment options when participants have a chronic condition [56]. Recent studies suggest that N-of-1 trials are effective tools for improving therapeutic precision, and they are widely accepted by patients and clinicians as an effective modality because they are patient-centred [56, 57]. They also have proven value in guiding a more effective prescription [55, 57, 58]. In the era of ‘personalised medicine’, they are becoming more popular. It is increasingly clear that ‘one size does not fit all’, particularly in complex interventions like diabetic footwear design and modifications.

In this proposed study, participants will have an initial assessment with the principal investigator, having been referred from the high-risk foot service. The initial assessment will include the selection of appropriate footwear, measuring, casting and 3D scanning of feet and technical specification of footwear and insole that reflects participant’s preferences. Barefoot static and dynamic pressure and in-shoe pressure measurements will be carried out. Current (standard) footwear, which may be a regular retail shoe, orthopaedic footwear, post-op shoes or cam-walkers or moon boots with or without insoles (custom or prefab), will be used as the control arm for the trial.

The second assessment will be done once the footwear and insole are ready for fitting (generally within 4 weeks after the initial assessment and measurement). In-shoe pressure analysis will be carried out in the new footwear and insole, which may undergo minor or major modification to achieve desired offloading efficacy. Participants will be assessed for walking comfort and satisfaction with their new footwear. Scores will be recorded on a Likert scale [59]. A third consultation will be arranged 2 weeks later. New footwear-wearing instructions will be provided to the participants, including contact details for an emergency or experiencing any adverse effect from the new footwear.

In the third assessment, the participant’s feet will be assessed for any redness or rubbing and any discomfort from the footwear. The participant’s self-reported wearing period data will be collected and analysed for wear patterns and frequency. The footwear will be assessed for any unusual wear marks or pressure points. Necessary adjustments will be made, and the fourth review session will be booked for a monthly visit.

During the fourth assessment, the participant’s feet and footwear will be assessed again. Participants’ satisfaction with the footwear will be recorded and compared with the participant’s self-reported wearing period data for the previous month. A similar process will follow, and another monthly appointment will be made with the researcher.

In the fifth assessment, a similar process will follow as the previous review, and this is the endpoint of the study. Participants will be asked about the walking comfort and likeliness of footwear and suitability for the intended application. Overall feedback and any comments from the participants on the footwear will be recorded. Any repair or adjustments to the footwear and insoles will be carried out, and they will be given contact details for any future repair and follow-up reviews.

Double-blinding is not feasible in this study design, given the nature of the intervention and secondary outcomes. Blinding is recommended in N-of-1 trials, but it is not mandatory [52]. In this proposed study design, participants will need to be aware of the prescribed footwear in order to provide feedback on acceptance. Features of the footwear and insoles may be easily identifiable by clinicians in the team. However, the statistician will remain blinded, and this study design can be termed a single-blind trial [60, 61].

Reporting standard

The quality of any study is dependent on the reporting standard of the study. To increase validity and acceptability, this N-of-1 trial will report data as per CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement [54].

The rationale for the N-of-1 trial

Patient adherence is key for successful offloading initiatives of the neuropathic diabetic foot. Footwear is an integral part of clothing. Patient preferences play a vital role in footwear usage and adherence to recommendations. Therefore, a patient-centred study design that can recommend a precise prescription on personalised therapy/devices is important. The N-of-1 trial design is unique in that it allows a focused assessment of patient preferences and circumstances. This is also beneficial for personalised treatment decisions for patients with chronic conditions [56]. There is a direct clinical application in individualising each participant’s treatment with outcomes generalisable to a broader patient population [56].

The effectiveness of offloading will be measured using the in-shoe plantar pressure analysis system. Using in-shoe plantar pressure measurements and [62] analysis is the gold standard in footwear-based pressure reduction studies [31, 63].

This trial methodology is preferable to participants as they feel more involved in treatment decisions and see changes being made in response to their feedback [51].

Rationale for control

The primary outcome measure is the reduction of forefoot peak plantar pressure. The control will be participants’ existing, usual footwear and insoles in the form of regular, orthopaedic or post-op footwear. This will form the baseline data of in-shoe plantar pressure measurements to be compared against the new footwear and insole to evaluate offloading efficacy. Hence, the choice of a control arm is essential, but in this case, the patient is their own control.

Study setting

Proposed physical sites are high-risk foot services (HRFSs) of the following hospitals and a private podiatry clinic:

  1. 1.

    Offloading clinic of Nepean Hospital, Nepean Blue Mountains Local Health District

  2. 2.

    St Vincent’s Hospital Sydney, St Vincent’s and Mater Health Network

  3. 3.

    Western Sydney Podiatry, Penrith, NSW 2750

Eligibility criteria

Inclusion criteria

Participants will be adults (≥18 years) with type 1 or type 2 diabetes, peripheral neuropathy and recently healed plantar forefoot ulcer. Participants must have at least one or more forefoot deformities such as claw/hammer toes, crossover toes, hallux valgus, hallux amputation, limited joint mobility, pes planus or pes cavus and bony prominences at metatarsal heads. Participants will have required a referral for orthopaedic footwear (either custom-made or prefabricated medical-grade footwear with or without modification) and custom-made insoles and have adequate English communication skills to comprehend the study procedures and provide informed consent.

Exclusion criteria

Exclusion criteria will be bilateral amputation (proximal to the trans-metatarsal joint), active or inactive Charcot foot, healed heel ulcers, midfoot deformities, use of walking aid for offloading the foot or severe illness, such that the participant may not survive the study period. Details are provided in the trial flow chart.

Participant’s consent process

The participant will meet with the investigator prior to completing informed consent. The investigator will explain the rationale for the study, what participation will involve, follow-up requirements if applicable and any side effects or risks. Questions from the participant will be encouraged. The participant information sheet (PIS) will be provided and discussed with the participant. The participant may wish to consider their decision or discuss it with other parties, and in that case, another visit with the investigator can be arranged. The participants will be advised that they can withdraw from the study at any time without explanation or prejudice to future care. If willing, the participant will be asked to sign the informed consent form. The principal investigator for each site will sign the PIS after the participant has signed.


Choice of comparisons

In this trial, participants’ existing footwear, insoles or offloading devices are the comparators. Participant’s current (standard) footwear, which may be regular retail shoes, orthopaedic footwear, post-op shoes or cam-walkers or moon boots with or without insoles (custom-made or prefabricated), will be used as the control arm for the trial.

Intervention description

Footwear and insole are the interventions in this trial which are personalised and can be modified further to improve PPP offloading and increase adherence [39, 40]. Participants are required to select a preferred style of footwear and report on the activities for which they intend to wear the footwear. The choices of footwear are either prefabricated orthopaedic footwear with or without modification and fully custom-made orthopaedic footwear, which is made from individual foot measurements and 3D scans of the foot and leg. The insoles will be designed in response to foot assessment data, a foam impression box and a 3D scan of the individual foot. The insoles will be manufactured using conventional manufacturing or 3D printing method. Participants will be provided with instructions for wearing the footwear and insoles. The footwear and insole suitability for the participants will be carefully checked at the t1 appointment by the researcher and also by the referring podiatrist, which is part of the regular clinical protocol. This process will be continued during each visit to ensure they are suitable for the participant. The modification of footwear, insole and in-shoe plantar pressure measuring will continue until an acceptable pressure reduction is achieved and the participant is satisfied with them. In the unlikely event that an adverse effect is observed from the provided footwear and insole, the participant will be asked to stop using them until a further assessment is conducted by the researcher and the treating multidisciplinary team.

Strategies to improve adherence to interventions

The interventions in this trial are therapeutic footwear and insole that are personalised and can be modified further when needed. These are wearable items of clothing for the participant. Participants’ preferences and the suitability of use will be considered in the selection of footwear interventions. There will be regular follow-up with participants, and participants’ self-reported data on adherence and satisfaction with the footwear and insole will be collected at each appointment. Participants will be given the motivation to adhere to the therapies by the researcher and other research team members, including explanations of the benefits of the devices and the adherence.

Provisions for post-trial care

These participants are at high risk of foot re-ulceration and are advised to be under regular podiatry care either at the community health clinics or their private podiatry clinics. They are also advised to visit the nearest high-risk foot services for any unlikely incident with their feet, such as an active wound or infection, with a referral from their GP or via the emergency department of the respective hospital. Participants will be advised to undergo twelve-weekly reviews with their pedorthists to ensure the footwear and insoles are repaired and optimally maintained.


The primary outcome is a reduction of PPP at the accepted level according to the protocol (<200kPa or 30% reduction from the baseline/control) [64]. The outcome will be measured by using an in-shoe pressure analysis (F-Scan® system by Tekscan® [65]).

The participants will also undergo in-shoe plantar pressure measurements at each fitting and review appointment, where they need to walk up to 12 m at a self-selected pace that represents their regular pace of walking and is consistent during each measurement. F-Scan® sensors will be calibrated at ‘Walk’ calibration, and the body weight of the participant will be recorded each time during the analysis.

The secondary outcome is adherence (recorded from the participant’s self-report on the wearing period) and participant’s satisfaction with the provided footwear and insoles (in terms of walking convenience and aesthetics, to be measured by using a Likert scale [59]).

Participant timeline

This project will last between 3 and 4 months, including the initial assessment, fitting of footwear and insoles and then at least three reviews outlined in the trial design flowchart in Fig. 1. The details of the timelines are t0, initial consultation; t1, 1st fitting appointment after the initial consultation; t2, 2-week review from fitting appointment; t3, 4 weeks from the 2nd review appointment; and t4, 4-week review from the 3rd review appointment.

Sample size

Twenty-one participants [51] from the HRFSs of two major public hospitals and their affiliated community clinics (Nepean Hospital, St Vincent’s Hospital Sydney) and a private podiatry clinic (Western Sydney Podiatry) in Sydney will be recruited for the study. A sample size calculation is not possible due to the non-existence of a well-validated Quality of Life Scale (QOLS) for the target population. The QOLS measures an individual’s satisfaction, perceptions of control, involvement, commitment and work-life balance regarding an individual’s personal perception. Previous studies [51, 66,67,68] utilising the N-of-1 methodology have recruited between 10 and 25 participants.


Participants will be recruited from the aforementioned HRFSs and the private podiatry clinic. Potential participants will be identified by interdisciplinary team members of the HRFSs, including endocrinologists, pedorthists and podiatrists. Participants will then be invited to participate.

Accounting for potential bias, confounding factors and missing information

There is a potential risk of biasing the results for the researcher also being the treating clinician. However, the statistician will remain blinded to the condition of the participant. The participant will also remain de-identified to the statistician, including the footwear and insole design features prescribed to that specific participant. The study is non-randomised, and any missing data will be handled through ‘as treated’ analysis. The in-shoe plantar pressure measurement will be done by using the F-Scan® system by Tekscan® [65] and the F-Scan® research software 7.0. The software generates the pressure analysis report without the clinician’s intervention. The report is based on sensors calibration data and actual interaction of pressure between the foot, insole and footwear. Thus, the report remains independent of external influence to give a true reflection of the offloading efficacy of the footwear and insole’s design and subsequent modifications. Participant’s self-report on perceived clinical outcomes regarding plantar pressure offloading (<200kPa or 30% reduction from the baseline/control), suitability of the footwear and insoles and the review feedback from the treating podiatrists in the high-risk foot services will also reduce the risk of bias.

Data collection

Each participant’s medical history, details of their foot assessment and comorbidities will be recorded in Qualtrics software [69], either directly into Qualtrics or from a paper-based case report form (CRF) to Qualtrics. This information will be obtained from the treating high-risk foot service with the participants’ consent. Participants’ preferences and adherence-related information will also be recorded in the same software for analysis following a similar data entry process. Plantar pressure data and shoe wear period data will be collected at each appointment with the researcher. Persons will be de-identified/anonymised before sending the data to the statistician.

Data management

Each participant will receive a study enrolment number, which will be used on an electronic spreadsheet. This way, participants can be re-identified by utilising the study enrolment number when further data collection or clarification is required. Once collated, data will be non-identifiable.

Data management and storage will be maintained in line with the National Health and Medical Research Council’s (NHMRC) ethics requirements [70]. Any hard copy, such as the participant’s signed consent form, CRF’s will be scanned and stored in the form of an electronic copy, and hard copies will be disposed of in a locked confidentiality bin. Electronic data will be stored on a password-protected computer with an up-to-date version of Trendmicro Maximum Security antivirus software. For each site, a Research Data Management Plan (RDMP) form will be maintained. Initial data will be stored at Southern Cross University (SCU)-approved data storage system for analysis purposes, and towards the end of the project, the data will be stored at SCU-approved and recommended data repositories.

Data will be archived for a period of 15 years after study completion, and this is the maximum recommended period of data archive period by NHMRC ethics requirements guidelines. This period will allow for conducting any follow-up study if the opportunity arises. After that period, electronic data will be securely erased.

Data analysis

Both descriptive and inferential statistical techniques will be used in this research. In the descriptive analysis, patient characteristics, as well as adherence/wearing time based on the participant’s satisfaction with the footwear and insoles, will be summarised. Under the statistical inference, a paired sample t-test will be used to compare the significant difference in plantar pressure between the custom-made footwear and baseline or control footwear. Two independent samples t-tests will be applied to compare patient characteristics between low- and high-adherence groups as well as participant’s compliance data and the clinician’s recommended data. In addition, the independent samples t-test will be used to compare the demographics and clinical features of the patients admitted to public and private clinics. Furthermore, the Wilcoxon signed-rank test would be used to compare adherence and wearing time between both follow-up moments and baseline. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the statistical significance will be set at p<0.05 with a confidence limit at 95% in a two-tailed fashion. For the qualitative data analysis, a thematic analysis will be used, and the software NVivo (version 12) will be utilised for that purpose.

Matching and sampling strategies

The participants are their own controls, so all data (plantar pressure data) will be matched within the participants for the intervention and control arms of the study.

Plans to give access to the full protocol, participant-level data and statistical code

The full study protocol, de-identified participant-level data and statistical code can be available by contacting the author.

Oversight and monitoring

Research governance and ethics

This multisite trial is administered by SCU and NBMLHD HREC and the RGOs of St Vincent’s Hospital Sydney and Nepean Hospital. The ethics have been approved by NBMLHD and the SCU HREC. The approval numbers are 2020/ETH02250 and 2020/093, respectively. The trial is conducted in accordance with the NHMRC guideline [70].

Written informed consent is obtained from each participant by one of the research teams of the respective site at the time of initial assessment and baseline information collection. A copy of the consent form can be available by contacting the corresponding author.

Trial management and data monitoring committee

The named authors in this article will be part of the trial management committee, which will also include each site-specific investigator and the collaborators reported in the study protocol. The chief investigator will ensure that every co-investigator is actively participating to ensure the participant’s safety and the trial quality is maintained. The lead chief investigator conducts the audit and reviews. Every principal coordinating investigator named in the project protocol for each site will be taking responsibility for the data monitoring.

Adverse event reporting and harms

Risk in this study relates to the use of new footwear and insoles for the participant.

Participants may face the following risks:

  1. a.

    Risk of fall or feeling unbalanced with wearing new footwear and insole to start.

Risk mitigation: Participants will be assessed carefully for any potential risk of falls and heel height, and the rocker profile will be adjusted accordingly in the footwear to mitigate the risk of falls or improve balance. At the initial fitting stage, the principal investigator will walk with the participant and will show the appropriate way of walking in the new devices.

  1. b.

    Risk of developing a blister or pressure mark either on the plantar or dorsal surface of the foot and leg. This can be due to changes in volume in the foot or leg for swelling or changes in medications.

Risk mitigation: The principal investigator will ensure that the footwear and insole fit well on the participant’s foot without putting any pressure on the foot and leg. The footwear comes with removable spacer inlays, and the thickness of the insoles can be adjusted if needed. The participants will be given a written wearing information sheet with contact details in case of any emergency and advice to stop wearing them until having a review with any of the investigators.

  1. iii.

    Risk of feeling discomfort or feeling unhappy about wearing a new kind of shoe and insole which may be quite different to what the participant is generally used to. Sometimes, participants may have perceptions that the orthopaedic or therapeutic footwear may not be aesthetically as appealing compared to their regular footwear.

Risk mitigation: The participant will be fully involved in and informed about the process of designing and manufacturing the prescribed footwear and insoles relating to their foot conditions during the first appointment. They will have input on design, style and colour selections for the footwear as per their intended activity. The footwear and insoles for the study will be used from premium orthopaedic brands and manufacturers to ensure the best possible quality and appearance.

Frequency and plans for auditing trial conduct

This project is subjected to online audit tools of IRMA and REGIS for project progress, and project completion review is conducted yearly or before if the project is shorter than 12 months.

Plans for communicating important protocol amendments to relevant parties

Any changes that become necessary during the study period will be proposed and amended in the study protocol and be made available to the HREC committee of NBMLHD and SCU. The research governance offices (RGOs) of each study site will also be notified through the Research Ethics Governance Information Systems (REGIS). SCU HREC will be reported through the Integrated Research Management Application (IRMA).

Dissemination plans

Findings will be published in relevant scientific journals and presented at scientific meetings as well as in a PhD thesis.


A patient-centric study design for footwear intervention in people with diabetes is non-existent [40, 71]. National and international guidelines [35, 72] recommend footwear and insole features to prevent foot ulcer occurrence and recurrence in people with diabetes. They also highlight the importance of adherence to them for improved clinical outcomes, but the guideline on improved adherence is non-existent. Participant satisfaction and adherence to the prescribed footwear are vital to achieving the desired clinical outcome [40].

Footwear is an integral part of the wardrobe for every individual irrespective of gender and activity level. Consideration of participant expectations, geographical and socioeconomic factors, effective education on footwear and activity-specific device designs are important considerations for a personalised-treatment approach for increased adherence [40]. This proposed N-of-1 trial is set to bridge the gap in current clinical practice through evidence-based recommendations to improve offloading efficacy and adherence to the prescribed footwear and insoles in people with diabetes and neuropathy.


The study period is within the COVID-19 restriction in New South Wales, which may affect the study operation and the number of participant recruitment. It may be inconvenient for some potential participants. For example, hospital outpatient department visits require mandatory vaccination for eligible persons and a PCR test conducted within 72 h of the clinic visit.

Trial status

The trial has been started in two study centres (Western Sydney Podiatry clinic since May 2021 and St Vincent’s Hospital since July 2021). Participant recruitment is expected to be completed by April 2022 in all study centres.


Pedorthist: A person who provides medical-grade footwear and/or orthotic appliances and appropriate advice to a patient after assessment and analysis of the patient’s problem(s). This includes the provision of prefabricated footwear, modification of prefabricated footwear, custom-designed and manufactured footwear and/or orthotic appliances and advice on the need and application of medical-grade footwear, orthotic appliances and other footwear.

Availability of data and materials

The datasets during the study are available from the corresponding author on a reasonable request. All data will be de-identified before making it available to authorised parties.



Analysis of variance


Case report form


Participant information sheet


Human Research Ethics Committee


High-risk foot service


Integrated Research Management Application


Nepean Blue Mountains Local Health District


National Health and Medical Research Council


Peak plantar pressure


Quality of Life Scale


Research Data Management Plan


Research governance office


Southern Cross University


  1. NSW HE. Orthotics & Medical Grade Footwear Equipment Request Form. 2014. Available at:

    Google Scholar 

  2. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005;366:1719.

    Article  Google Scholar 

  3. Waaijman R, de Haart M, Arts ML, Wever D, Verlouw AJ, Nollet F, et al. Risk factors for plantar foot ulcer recurrence in neuropathic diabetic patients. Diabetes Care. 2014;37:1697.

    Article  Google Scholar 

  4. Ghanassia E, Villon L, Thuandit Dieudonné JF, Boegner C, Avignon A, Sultan A. Long-term outcome and disability of diabetic patients hospitalized for diabetic foot ulcers: a 6.5-year follow-up study. Diabetes Care. 2008;31:1288.

    Article  Google Scholar 

  5. Peters EJ, Armstrong DG, Lavery LA. Risk factors for recurrent diabetic foot ulcers: site matters. Diabetes Care. 2007;30:2077.

    Article  Google Scholar 

  6. Pound N, Chipchase S, Treece K, Game F, Jeffcoate W. Ulcer-free survival following management of foot ulcers in diabetes. Diabetic Med. 2005;22:1306.

    Article  CAS  Google Scholar 

  7. Molines-Barroso R, Lázaro-Martínez J, Aragón-Sánchez J, García-Morales E, Beneit-Montesinos J, Álvaro-Afonso F. Analysis of transfer lesions in patients who underwent surgery for diabetic foot ulcers located on the plantar aspect of the metatarsal heads. Diabetic Med. 2013;30:973.

    Article  CAS  Google Scholar 

  8. Armstrong DG, Boulton AJ, Bus SA. Diabetic foot ulcers and their recurrence. New England J Med. 2017;376:2367.

    Article  Google Scholar 

  9. Lazzarini PA, O’Rourke SR, Russell AW, Derhy PH, Kamp MC. Reduced incidence of foot-related hospitalisation and amputation amongst persons with diabetes in Queensland, Australia. PLoS One. 2015;10:e0130609.

    Article  Google Scholar 

  10. Bandyk DF. The diabetic foot: pathophysiology, evaluation, and treatment. In: Seminars in vascular surgery: Elsevier; 2018. p. 43.

    Google Scholar 

  11. Cavanagh P, Boulton A, Sheehan P, Ulbrecht J, Caputo G, Armstrong D, et al. Letters-therapeutic footwear in patients with diabetes. JAMA. 2002;288:1229.

    Article  Google Scholar 

  12. Lázaro-Martínez JL, Aragón-Sánchez J, Álvaro-Afonso FJ, García-Morales E, García-Álvarez Y, Molines-Barroso RJ. The best way to reduce reulcerations: if you understand biomechanics of the diabetic foot, you can do it. Int J Lower Extrem Wounds. 2014;13:294.

    Article  Google Scholar 

  13. Bus SA. Foot structure and footwear prescription in diabetes mellitus. Diabetes Metab Res Rev. 2008;24:S90.

    Article  Google Scholar 

  14. Reiber GE, Vileikyte L, Ed B, Del Aguila M, Smith DG, Lavery LA, et al. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care. 1999;22:157–62.

    Article  CAS  Google Scholar 

  15. Carls GS, Gibson TB, Driver VR, Wrobel JS, Garoufalis MG, DeFrancis RR, et al. The economic value of specialized lower-extremity medical care by podiatric physicians in the treatment of diabetic foot ulcers. J Am Podiatr Med Assoc. 2011;101:93.

    Article  Google Scholar 

  16. van Schie CH. Neuropathy: mobility and quality of life. Diabetes Metab Res Rev. 2008;24:S45.

    Article  Google Scholar 

  17. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293:217.

    Article  CAS  Google Scholar 

  18. Hidmark A, Fleming T, Vittas S, Mendler M, Deshpande D, Groener J, et al. A new paradigm to understand and treat diabetic neuropathy. Exp Clin Endocrinol Diabetes. 2014;226:201.

    Google Scholar 

  19. Fernando M, Crowther R, Lazzarini P, Sangla K, Cunningham M, Buttner P, et al. Biomechanical characteristics of peripheral diabetic neuropathy: a systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure. Clin Biomechanics. 2013;28:831.

    Article  Google Scholar 

  20. Sawacha Z, Spolaor F, Guarneri G, Contessa P, Carraro E, Venturin A, et al. Abnormal muscle activation during gait in diabetes patients with and without neuropathy. Gait Posture. 2012;35:101.

    Article  Google Scholar 

  21. Ko S-u, Stenholm S, Chia CW, Simonsick EM, Ferrucci L. Gait pattern alterations in older adults associated with type 2 diabetes in the absence of peripheral neuropathy—results from the Baltimore Longitudinal Study of Aging. Gait Posture. 2011;34:548.

    Article  Google Scholar 

  22. Guiotto A, Sawacha Z, Guarneri G, Cristoferi G, Avogaro A, Cobelli C. The role of foot morphology on foot function in diabetic subjects with or without neuropathy. Gait Posture. 2013;37:603.

    Article  Google Scholar 

  23. Chen WM, Lee T, Lee PV, Lee JW, Lee SJ. Effects of internal stress concentrations in plantar soft-tissue--a preliminary three-dimensional finite element analysis. Med Eng Phys. 2010;32:324.

    Article  Google Scholar 

  24. Chao CY, Zheng Y-P, Cheing GL. Epidermal thickness and biomechanical properties of plantar tissues in diabetic foot. Ultrasound Med Biol. 2011;37:1029.

    Article  Google Scholar 

  25. Pai S, Ledoux WR. The compressive mechanical properties of diabetic and non-diabetic plantar soft tissue. J Biomech. 2010;43:1754.

    Article  Google Scholar 

  26. Chapman J. “Improving the design of the curved rocker shoe for people with diabetes” (PhD, University of Salford), vol. 253; 2014.

    Google Scholar 

  27. van Netten JJ, van Baal JG, Bril A, Wissink M, Bus SA. An exploratory study on differences in cumulative plantar tissue stress between healing and non-healing plantar neuropathic diabetic foot ulcers. Clin Biomech. 2018;53:86.

    Article  Google Scholar 

  28. Cavanagh PR, Ulbrecht JS. Clinical plantar pressure measurement in diabetes: rationale and methodology. Foot. 1994;4:123.

    Article  Google Scholar 

  29. Bennetts CJ, Owings TM, Erdemir A, Botek G, Cavanagh PR. Clustering and classification of regional peak plantar pressures of diabetic feet. J Biomech. 2013;46:19.

    Article  Google Scholar 

  30. Rao S, Saltzman CL, Yack HJ. Relationships between segmental foot mobility and plantar loading in individuals with and without diabetes and neuropathy. Gait Posture. 2010;31:251.

    Article  Google Scholar 

  31. Bus SA, Haspels ROB, Busch-Westbroek TE. Evaluation and optimization of therapeutic footwear for neuropathic diabetic foot patients using in-shoe plantar pressure analysis. Diabetes Care. 2011;34:1595.

    Article  Google Scholar 

  32. Bus SA. Priorities in offloading the diabetic foot. Diabetes Metab Res Rev. 2012;28:54.

    Article  Google Scholar 

  33. Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003;361:1545.

    Article  Google Scholar 

  34. Collings R, Freeman J, Latour JM, Glasser S, Paton J. Footwear and insole design features to prevent foot ulceration in people with diabetes: a systematic review protocol. JBI Database System Rev Implement Rep. 2017;15:1824.

    Article  Google Scholar 

  35. van Netten JJ, Lazzarini PA, Armstrong DG, Bus SA, Fitridge R, Harding K, et al. Diabetic Foot Australia guideline on footwear for people with diabetes. J Foot Ankle Res. 2018;11:2.

    Article  Google Scholar 

  36. Owings T, Apelqvist J, Stenström A, Becker M, Bus S, Kalpen A, et al. Plantar pressures in diabetic patients with foot ulcers which have remained healed. Diabetic Med. 2009;26:1141.

    Article  CAS  Google Scholar 

  37. Owings TM, Woerner JL, Frampton JD, Cavanagh PR, Botek G. Custom therapeutic insoles based on both foot shape and plantar pressure measurement provide enhanced pressure relief. Diabetes Care. 2008;31:839.

    Article  Google Scholar 

  38. Bus SA, Van Deursen R, Armstrong D, Lewis JE, Caravaggi C, Cavanagh P, et al. Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review. Diabetes Metab Res Rev. 2016;32:99.

    Article  Google Scholar 

  39. Collings R, Freeman J, Latour JM, Paton J. Footwear and insole design features for offloading the diabetic at risk foot—a systematic review and meta-analyses. Endocrinol Diabetes Metabolism. 2021;4:e00132.

    Article  Google Scholar 

  40. Ahmed S, Barwick A, Butterworth P, Nancarrow S. Footwear and insole design features that reduce neuropathic plantar forefoot ulcer risk in people with diabetes: a systematic literature review. J Foot Ankle Res. 2020;13:1.

    Article  Google Scholar 

  41. Praet SF, Louwerens J-WK. The influence of shoe design on plantar pressures in neuropathic feet. Diabetes Care. 2003;26:441.

    Article  Google Scholar 

  42. Preece SJ, Chapman JD, Braunstein B, Brüggemann G-P, Nester CJ. Optimisation of rocker sole footwear for prevention of first plantar ulcer: comparison of group-optimised and individually-selected footwear designs. J Foot Ankle Res. 2017;10:27.

    Article  Google Scholar 

  43. Rizzo L, Tedeschi A, Fallani E, Coppelli A, Vallini V, Iacopi E, et al. Custom-made orthesis and shoes in a structured follow-up program reduces the incidence of neuropathic ulcers in high-risk diabetic foot patients. Int J Lower Extrem Wounds. 2012;11:59.

    Article  Google Scholar 

  44. Busch K, Chantelau E. Effectiveness of a new brand of stock ‘diabetic’ shoes to protect against diabetic foot ulcer relapse. A prospective cohort study. Diabetic Med. 2003;20:665.

    Article  CAS  Google Scholar 

  45. López-Moral M, Lázaro-Martínez JL, García-Morales E, García-Álvarez Y, Álvaro-Afonso FJ, Molines-Barroso RJ. Clinical efficacy of therapeutic footwear with a rigid rocker sole in the prevention of recurrence in patients with diabetes mellitus and diabetic polineuropathy: a randomized clinical trial. PloS One. 2019;14:e0219537.

    Article  Google Scholar 

  46. Arts M, Waaijman R, de Haart M, Keukenkamp R, Nollet F, Bus S. Offloading effect of therapeutic footwear in patients with diabetic neuropathy at high risk for plantar foot ulceration. Diabetic Med. 2012;29:1534.

    Article  CAS  Google Scholar 

  47. Dahmen R, Haspels R, Koomen B, Hoeksma AF. Therapeutic footwear for the neuropathic foot: an algorithm. Diabetes Care. 2001;24:705.

    Article  CAS  Google Scholar 

  48. Bus SA, Waaijman R, Arts M, De Haart M, Busch-Westbroek T, Van Baal J, et al. Effect of custom-made footwear on foot ulcer recurrence in diabetes: a multicenter randomized controlled trial. Diabetes Care. 2013;36:4109.

    Article  Google Scholar 

  49. Paton JS, Stenhouse EA, Bruce G, Zahra D, Jones RB. A comparison of customised and prefabricated insoles to reduce risk factors for neuropathic diabetic foot ulceration: a participant-blinded randomised controlled trial. J Foot Ankle Res. 2012;5:31.

    Article  Google Scholar 

  50. Guldemond N, Leffers P, Schaper N, Sanders A, Nieman F, Willems P, et al. The effects of insole configurations on forefoot plantar pressure and walking convenience in diabetic patients with neuropathic feet. Clin Biomech. 2007;22:81.

    Article  CAS  Google Scholar 

  51. Nikles J, Mitchell GK, Schluter P, Good P, Hardy J, Rowett D, et al. Aggregating single patient (n-of-1) trials in populations where recruitment and retention was difficult: the case of palliative care. J Clin Epidemiol. 2011;64:471.

    Article  Google Scholar 

  52. Kravitz R, Duan N, Eslick I, Gabler N, Kaplan H. Design and implementation of N-of-1 trials: a user’s guide. Agency for healthcare research and quality, US Department of Health and Human Services; 2014.

    Google Scholar 

  53. Tate RL, Perdices M, Rosenkoetter U, Wakim D, Godbee K, Togher L, et al. Revision of a method quality rating scale for single-case experimental designs and n-of-1 trials: the 15-item Risk of Bias in N-of-1 Trials (RoBiNT) Scale. Neuropsychol Rehabil. 2013;23:619.

    Article  Google Scholar 

  54. Vohra S, Shamseer L, Sampson M, Bukutu C, Schmid CH, Tate R, et al. CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement. bmj. 2015;350:h1738.

    Article  Google Scholar 

  55. Schork NJ. Personalized medicine: time for one-person trials. Nature News. 2015;520:609.

    Article  CAS  Google Scholar 

  56. Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness research. J Clin Epidemiol. 2013;66:S21.

    Article  Google Scholar 

  57. Gabler NB, Duan N, Vohra S, Kravitz RL. N-of-1 trials in the medical literature: a systematic review. Med Care. 2011;49:761–8.

    Article  Google Scholar 

  58. Nikles CJ, Clavarino AM, Del Mar CB. Using n-of-1 trials as a clinical tool to improve prescribing. Br J Gen Pract. 2005;55:175.

    Google Scholar 

  59. Bertram D. Likert scales. Retrieved November 2: 2013; 2007.

    Google Scholar 

  60. Karanicolas PJ, Farrokhyar F, Bhandari M. Blinding: who, what, when, why, how? Can J Surg. 2010;53:345.

    Google Scholar 

  61. Price JD, Grimley EJ. N-of-1 randomized controlled trials (‘N-of-1 trials’): singularly useful in geriatric medicine. Age Ageing. 2002;31:227.

    Article  Google Scholar 

  62. Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine? Personalized Med. 2011;8:161.

    Article  Google Scholar 

  63. Arts M, Haart M, Waaijman R, Dahmen R, Berendsen H, Nollet F, et al. Data-driven directions for effective footwear provision for the high-risk diabetic foot. Diabetic Med. 2015;32:790.

    Article  CAS  Google Scholar 

  64. Bus SA, Lavery LA, Monteiro-Soares M, Rasmussen A, Raspovic A, Sacco IC, et al. Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020;36:e3269.

    Google Scholar 

  65. F-Scan System. 2019. Accessed Date 2019.

  66. Haines DR, Gaines SP. N of 1 randomised controlled trials of oral ketamine in patients with chronic pain. Pain. 1999;83:283.

    Article  CAS  Google Scholar 

  67. March L, Irwig L, Schwarz J, Simpson J, Chock C, Brooks P. n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. Bmj. 1994;309:1041.

    Article  CAS  Google Scholar 

  68. Sniehotta FF, Presseau J, Hobbs N, Araújo-Soares V. Testing self-regulation interventions to increase walking using factorial randomized N-of-1 trials. Health Psychol. 2012;31:733.

    Article  Google Scholar 

  69. software Qs. Qualtrics survey software. Available at:

  70. NHMRC. 2020. Available at:

  71. Bus S, van Netten J. A shift in priority in diabetic foot care and research: 75% of foot ulcers are preventable. Diabetes Metab Res Rev. 2016;32:195–200.

  72. Bus SA, Armstrong DG, Gooday C, Jarl G, Caravaggi C, Viswanathan V, et al. Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020;36:e3274.

    Google Scholar 

Download references


The site-specific investigators and co-investigators of the clinical trial sites in the HRFs and the private podiatry clinic.


As the footwear and insoles are part of the standard treatment for each participant, the funding will be provided by the funding source to which each participant has access. This includes HealthShare Enable NSW [1], private health funds, aged care packages, Closing the Gap or self-funded by participants based on their eligibility criteria. Foot Balance Technology (owned by the chief investigator) will provide support for the F-scan and MatScan systems and relevant sensors. There will be no cost to participants for the sensors.

Author information

Authors and Affiliations



SA is the chief investigator; he led the protocol development and managed the stakeholders’ relationship. AB contributed to the study design and protocol development. PB contributed to the study design and protocol development. AS contributed to the ethics application for the NBMLHD and SSA for the Nepean Hospital site and approval process. MZH contributed to the data analysis process. SN contributed to the study design conceptualisation and protocol development. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Sayed Ahmed.

Ethics declarations

Ethics approval and consent to participate

The ethical aspects of this research project have been approved by the Nepean Blue Mountains Local Health District (NBMLHD) Human Research Ethics Committee (HREC) and the Southern Cross University HREC. The approval numbers are 2020/ETH02250 and 2020/093, respectively. Written informed consent is obtained from each participant by one of the research teams of the respective site at the time of initial assessment and baseline information collection. A copy of the consent form can be available by contacting the corresponding author.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmed, S., Butterworth, P., Barwick, A. et al. Footwear and insole design parameters to prevent occurrence and recurrence of neuropathic plantar forefoot ulcers in patients with diabetes: a series of N-of-1 trial study protocol. Trials 23, 1017 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: