Efficacy and safety of two Ayurvedic dosage forms for allergic rhinitis: Study protocol for an open-label randomized controlled trial

Background Allergic rhinitis (AR) is an immune response of the nasal mucosa to airborne allergens and involves nasal congestion, watery nasal discharge, itching of the nose, and sneezing. The symptoms of allergic rhinitis may significantly affect a patient’s quality of life and can be associated with conditions such as fatigue, headache, cognitive impairment, and sleep disturbances. Various complementary and alternative medicine treatments have been used for this condition in clinical practice. The Ayurveda system of medicine is the most common complementary medicine system practiced in Sri Lanka. The aim of this study is to examine the efficacy and safety of a decoction used in traditional Ayurveda for allergic rhinitis and its ready- to-use freeze dried formulation in comparison to an antihistamine over a period of 4 weeks on relief of symptoms in allergic rhinitis. Study design This is a three-arm, open-label, non-inferiority, randomized controlled clinical trial enrolling patients with AR. Tamalakyadi decoction containing 12 ingredients (TMD12), used in traditional Ayurveda and its freeze-dried formulation are the test products. The efficacy and safety of the two Ayurvedic dosage forms will be tested against the antihistamine loratadine. Patients with symptoms of AR will be allocated randomly into the three arms after a 1-week run-in period and the medications will be given orally for 28 days. Total Nasal symptom Score (TNSS) of the patients will be used as the primary efficacy endpoint. TNSS will be recorded and compared between the three arms prior to visit 1, at the end of 28 days, and end of the first and second months of follow-up. Symptom scores of daytime nasal symptoms, night time nasal symptoms, non-nasal symptoms and health-related quality of life questionnaire are used as secondary end points. Discussion This clinical trial will be able to provide evidence-based scientific data on Ayurvedic dosage form, TMD12, and the freeze-dried formulation in the treatment of allergic rhinitis. This trial is expected to develop capacity to scientifically evaluate various Ayurvedic treatments that are claimed to have efficacy in treatment of various disease conditions. Trial registration ISRCTN18149439 (6 May 2019).


Plain English Summary
Background and study aims Allergic rhinitis is an immune response of the nasal mucosa (lining of the nasal cavities) to airborne allergens and involves nasal congestion, watery nasal discharge, itching of the nose and sneezing. Allergic rhinitis is commonly defined as seasonal or perennial, depending upon whether symptoms occur at defined yearly intervals or throughout the year, respectively. Allergic rhinitis is not life threatening, but it is an annoying and disturbing disease for the patient due to its chronicity and aggravation when exposed to allergic agents. Furthermore allergic rhinitis is a considerable cause of widespread morbidity, medical treatment costs, reduced work productivity and lost school days. The symptoms of allergic rhinitis may significantly affect a patient's quality of life and can be associated with conditions such as fatigue, headache, cognitive impairment and sleep disturbances. Appropriate management of allergic rhinitis is an important component in the effective management of coexisting or complicated respiratory conditions such as asthma, sinusitis and sleep apnea. In this context, various complementary and alternative medicine treatments have been used for this condition in clinical practice. The Ayurveda system of medicine is the most common complementary medicine system in Sri Lanka. The aim of this study is to find out whether the use of two preparations (decoction and its freeze dried powder) over a period of 4 weeks is able to cure the symptoms of allergic rhinitis.
Who can participate? Male and female patients aged 18 to 65 with allergic rhinitis What does the study involve? Participants are randomly allocated to receive either one of two Ayurveda treatments (traditional herbal decoction or a sachet containing freeze dried ingredients of herbal decoction) or the antihistamine loratidine for 4 weeks. Nasal symptoms are assessed at the start of the study, after four weeks of treatment, and after one month and two months of follow up.
What were the possible benefits and risks of participating? The participants receive information and advice from a specialized medical team. In addition their participation may help to develop an Ayurveda drug treatment for allergic rhinitis.
Where is the study run from? National Ayurveda Teaching Hospital (Sri Lanka) When is the study starting and how long is it expected to run for?

Condition
Allergic rhinitis Intervention This will be a three-arm open-label non-inferiority randomized control trial in patients with allergic rhinitis. Consecutive consenting sample method will be followed to select participants of the arms for the study. A blocked design will be used, using an online statistical computing web programming to generate the randomization schedule (research randomizer https://www.randomizer.org [https://www.randomizer.org] ). Eligible subjects will be randomly assigned to Arm I, Arm II and Arm III to receive herbal decoction, freezedried powder of herbal decoction and antihistamine for 28 days.
The patients of Arm I will be treated with herbal decoction (Tamalakyadi decoction), 120 ml twice a day after meals. Arm II patients will be treated with 6 g of freeze-dried powder of herbal decoction. The powder should be dissolved in 240 ml of hot water and should take 120 ml twice a day after meals. The patients of Arm III will receive antihistamine (loratidine 10 mg) at night taken with 240 ml of water. Patients belong to three arms have to visit the clinic weekly.
Total Nasal Symptom Score (TNSS) and IgE level of patients will be the primary efficacy endpoints. The mean difference in TNSS and IgE level will be compared between the three arms as the primary endpoints at the end of 28 days. The TNSS will be again analyzed after 1 month and 2 months of treatment at follow-up visits.
Mean score of daytime nasal symptoms, nighttime nasal symptom, non-nasal symptoms and Health-Related Quality of Life score will be used as secondary endpoints in the clinical trial. These symptom scores will be https://www.isrctn.com/ISRCTN18149439?q=kamal&filters=&sort=&offset=1&totalResults=6&page=1&pageSize=10&searchType=basic-search 5/8 analyzed by using the information mentioned in rhinitis diary card of the patient. This diary cards will be collected weekly at the clinic.
Follow up -patients will be assessed after 1 month and 2 months at the clinic without a drug intervention. Primary outcome measure 1. Nasal symptoms (watery rhinorrhea, sneezing, nasal obstruction, nasal itching) measured using the Total Nasal Symptom Score (TNSS) of allergic rhinitis patients at baseline and the end of intervention (after four weeks, after one month of follow up and two months of follow up) 2. Serum Immunoglobulin E level measured using chemiluminesent enzyme immunoassay (EIA) at baseline and after intervention Secondary outcome measures 1. Mean score of daytime nasal symptom score 2. Mean score of nighttime nasal symptom score 3. Mean score of non-nasal symptoms Patient self-rated symptom scores (daily rhinitis diary card) and allergic rhinitis grading symptoms collected on a weekly basis during the assessment period. The measurement of symptoms on a 4-point rating scale with the following definition will be used: • 0 = absent symptoms (no sign/symptom evident) • 1 = mild symptoms (sign/symptom clearly present, but minimal awareness; easily tolerated) • 2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable) • 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping