Efficacy of moxibustion for pre- or stage I hypertension: study protocol for a pilot randomized controlled trial
© Shin et al.; licensee BioMed Central Ltd. 2012
Received: 18 July 2012
Accepted: 26 September 2012
Published: 8 October 2012
Hypertension is a risk factor for cardiovascular disease, and the prevalence of hypertension tends to increase with age. Current treatments for hypertension have adverse side effects and poor adherence. The purpose of this study is to evaluate the effects of moxibustion on blood pressure in individuals with pre- or stage I hypertension.
Forty-five subjects with pre- or stage I hypertension will be randomized into three groups: treatment group A (2 times/week), treatment group B (3 times/week), and the control group (non-treated group). The inclusion criteria will be as follows: (1) aged between 19 and 65 years; (2) prehypertension or stage I hypertension (JNC 7, Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure); (3) the participants are volunteers and written consent obtained.
The participants in the treatment group A will undergo indirect moxibustion 2 times per week for 4 weeks, and the participants in the treatment group B will undergo indirect moxibustion 3 times per week for 4 weeks. The participants in the control group (non-treated group) will maintain their current lifestyle, including diet and exercise. The use of antihypertensive medication is not permitted. The primary endpoint will be a change in patient blood pressure. The secondary endpoints will be the body mass index, lipid profile, EuroQol and Heart Rate Variability. The data will be analyzed with the Student’s t-test and analysis of variance (ANOVA) (p < 0.05).
The results of this study will help to establish the optimal approach for the care of adults with pre- or stage I hypertension.
Clinical Research Information Service KCT0000469
KeywordsMoxibustion Hypertension Prehypertension
It is estimated that in 2025, 1.56 billion adults will have hypertension . According to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure(JNC-7), patients with a blood pressure of 120–139/80–89 mmHg have prehypertension . A recent study demonstrated that people with prehypertension were more likely to develop hypertension than those with normal blood pressure over the 50-year follow-up period . According to a longitudinal population-based US cohort study, prehypertension increases the risk of developing cardiovascular diseases . The results of another study suggest that prehypertension increases the risk of myocardial infarction, stroke, cardioplegia, and cardiovascular death in women .
Moxibustion involves the application of ignited mugwort (Artemisia vulgaris) at acupoints or other specific parts of the body to treat or prevent diseases. This technique is typically used to treat and prevent cold syndrome, deficiency conditions and chronic diseases . Moxibustion can cause tissue damage as a result of skin irritation or even skin burns due to the thermal stimulation, which is performed at various temperatures. The thermal stimulation can also cause inflammatory responses and vascular changes. According to the findings of previous studies of moxibustion, mediators such as histamine and substance P are secreted, and this process promotes angiectasis . It seems that inflammatory reactions that affect vascular activity may ease various cardiovascular diseases, including hypertension .
There are few published randomized controlled trials (RCTs) concerning moxibustion treatment for prehypertension. A systematic review on the effects of moxibustion on hypertension revealed no evidence that moxibustion is beneficial to people with hypertension. However, the differences between specific and non-specific effects should be examined in a future study that includes appropriate control groups .
Aims of the study
The aims of this pilot study are to evaluate the effects of moxibustion on blood pressure in patients with pre- or stage I hypertension, to test the methods used and to calculate the sample size required for future randomized trials.
This study will be a prospective randomized controlled trial, and participants will be recruited from Woo-suk University Hospital using notices at the hospital and newspaper advertisements.
This study has been registered with the ‘Clinical Research Information Service,’ Republic of Korea, which is a registry in the WHO Registry Network (KCT0000469).
The systolic and diastolic blood pressures will be measured in the arm using an automatic blood pressure meter (HD-505, Jawon Medical Co, Kyungsan City, Korea). The subjects will be fitted with a BP cuff on both arms. A trained researcher will measure the blood pressure carefully in the arm with higher BP while the subject is in the seated position. The blood pressure will be measured three times after the subject has rested for at least 10 min. All BP measurements will be taken in a temperature-controlled room. The three measurements will be carried out at 5-min intervals. The mean of these three measurements will be used in the data analysis. The participants will be instructed not to drink caffeinated drinks such as coffee or tea and not to exercise, smoke or eat 2 h before the blood pressure test. In addition, they will be instructed to avoid drinking heavily the day before the test .
The practitioner has had more than 3 years of clinical experience since completing 6 years of study at the College of Korean Medicine and has received a Doctor of Korean Medicine.
This study is designed as a pilot study to calculate the appropriate sample size for future randomized clinical trials. Allowing for a 20% dropout rate, each group will include 15 participants, which is the minimum sample size necessary to evaluate the effect of moxibustion [13, 14]. In this study, stratified randomization will be performed by classifying subjects into age and sex by an online centralized randomization service.
This protocol adheres to the principles of the Declaration of Helsinki and has been approved by the institutional review boards of the Woo-suk University Hospital, where the study will take place (WSOH IRB 1205-02). Before any treatment is given, written consent will be obtained from each participant. All patients will have the right to withdraw from the trial at any time.
Inclusion criteria were as follows: (1) aged between 19 and 65 years; (2) pre- or stage I hypertension (JNC 7); (3) the participants are volunteers, and written consent was obtained.
Patient inclusion and exclusion criteria
Aged between 19 and 65 years
Taking medications to control blood pressure
Pre- or stage 1 hypertension (JNC 7)
-Systolic blood pressure between 120 and 159 mmHg
History of cerebrovascular disease, cardiovascular disease, malignant tumors, kidney diseases, liver diseases, thyroid gland diseases, active tuberculosis, or other infectious diseases
- Diastolic blood pressure between 80 and 99 mmHg
Diabetic patients taking insulin or anti-diabetic medications
The participants are volunteers and written consent obtained
Drug or alcohol dependence
Taking hemorrhagic disease and anticoagulation medications (excluding aspirin)
Receiving systemic steroid therapy or immunosuppressive therapy
Taking medications that could affect blood pressure such as central nervous system depressants or stimulants
Pregnancy or the possibility of pregnancy
Hypersensitivity reactions following moxibustion therapy
Received oriental medicine treatment related to hypertension in the past month
Participants deemed unsuitable for the trial, as judged by the person in charge of the clinical trial.
Treatment group A
The subjects receiving moxibustion treatment will be treated 2 times per week.
During each moxibustion treatment, each acupoint will be treated five times. The moxibustion treatment will last for 25 min. The treatment will continue for 4 weeks. Following the procedures used in several previous studies [11, 15, 16], acupuncture needles will be inserted bilaterally into three acupuncture points (LI11, ST36, GB39) on the four peripheral extremities and unilaterally into two points (CV4, CV12) in the abdominal region. Indirect moxibustion (Manina, Haitnim Co., Ltd., Korea. 19 mm diameter and 21 mm height) will be used in the trial.
Treatment group B
The format will be exactly the same as those for treatment group A, but the subjects receiving moxibustion treatment will be treated three times per week.
Control group (untreated group)
The control group (untreated group) will receive no treatment. The subject in this group will be asked to maintain their normal lifestyle, including diet, exercise and workload.
Permitted and prohibited concomitant treatments
Brochures containing information on dietary changes, living habits, and exercise regimens that help prevent and alleviate hypertension will be distributed to all groups, and the subjects will decide for themselves whether to incorporate the suggested changes into their daily lives.
All groups will be prohibited from undergoing active treatment to lower the blood pressure for the duration of their participation in this clinical trial. After the completion of the clinical trial, during the assessment period, the subjects will be allowed to decide for themselves whether to receive additional treatment. Any other related information will be recorded in detail.
The use of birth control pills and central nervous system stimulants or depressants, which can affect blood pressure, will remain prohibited. The practitioner will be allowed to converse with the subjects about daily care and treatment details while carrying out the required examination.
The primary outcome measurement in this study is the change in blood pressure before randomization (baseline) and 4 weeks after randomization. Blood pressure will be taken at every visit.
The secondary outcome measures will be the mean pulse pressure, body mass index (BMI), heart rate variability (HRV), the Modified Stress Response Inventory (SRI-MF), the Pittsburgh Sleep Quality Index (PSQI), the Fatigue Severity Scale (FSS), EuroQol (EQ-5D), general assessments and blood tests including fasting blood sugar (FBS), uric acid, lipid profile, high sensitivity C-reactive protein (hs-CRP), liver function test (LFT), hemoglobin A1c (HbA1C), and complete blood count (CBC).
Content of baseline and follow-up questionnaires
End of treatment
at 4 weeks after randomization
at 8, 12, 16, 20 and 24 weeks after randomization
Demographic information taking
BMI (body mass index)
NDI (neck disability index)
PSQI (Pittsburgh Sleep Quality Index)
HRV (heart rate variability)
Questionnaire of pattern identification
SRI-MF (modified form of the Stress Response Inventory)
FSS (Fatigue Severity Scale)
Follow-up tests will be conducted at 8, 12, 16, 20 and 24 weeks after randomization. The follow-up assessment is designed to evaluate the long-term effects of moxibustion.
The results of the intention-to-treat (ITT) analysis will be used to assess the validity of the study as a whole. The per-protocol (PP) analysis results will be used as a reference. The ITT analysis will be used as the main safety assessment technique.
Continuous data will be represented by the average, standard deviation, minimum value, and maximum value, whereas categorical data will be represented by a frequency table. For the comparison of the results among the groups, the analysis of variance (ANOVA) test will be used when the data are normally distributed; the Kruskal-Wallis test will be used otherwise. In addition, the chi-square test will be performed for categorical data.
After 4 weeks, the differences in systolic and diastolic pressure will be summarized for each group using descriptive statistics, including the median, average, standard deviation, and interquartile range. In addition, we will evaluate the effectiveness of the treatment using an analysis of covariance as the dependent variable, the baseline score as the covariate, the group as the fixed factor, and the hypertension stage as the stratified variable. In addition, we will compare the results for the stratified groups with the results for the whole subject pool (non-stratified) to determine whether hypertension stage is a suitable stratification variable. The differences in the systolic pressure and diastolic pressure following the treatment for each group will be analyzed using a paired t-test or a Wilcoxon signed rank test, and the 95% confidence interval will be presented. To assess the difference in the tendency for each visit, repeated measures analysis of variance will be performed. A significance level of 5% will be used in all analyses.
The average pulse pressure, change in the baseline blood pressure following the treatment, BMI, EQ-5D, Ankle Brachial Pressure Index(ABI index), Brachial-Ankle Pulse wave velocity(PWV index), heart rate variation (LF/HF ratio, TP, VLF, LF, HF, heart rate, SDNN, LF norm, HF norm), and blood test results will be analyzed using the same techniques used to analyze the validity of the assessment variable. To determine whether there are differences in the distribution of the change in symptoms among the groups, analysis will be performed on each item using the chi-squared test.
All adverse reactions manifested will be listed with detailed explanations. The frequency of abnormal reactions that are correlated with the treatment and abnormal reactions that do not have such correlations will be recorded. A Fisher’s exact test will be performed to determine whether there are any differences among the groups with respect to the incidence of abnormal reactions as reported by the subjects. Furthermore, technical analysis will be performed to identify differences in the degree of severity and in the type of abnormal reactions among the groups.
The safety evaluation will be based on adverse events, which are expected to include blisters, redness, and burns. Adverse reactions refer to undesirable and unintentional signs (e.g., abnormal test results), symptoms or diseases following the treatment. There does not necessarily have to be a cause and effect relationship with the treatment. The subjects will be instructed to voluntarily report any information regarding abnormal reactions to the practitioner on a regular basis.
Any adverse events during treatment will be recorded. When abnormal reactions appear, the date of appearance, the date of disappearance, the degree of the abnormal reaction, measures taken related to the treatment, correlation with the treatment, names of suspicious drugs taken outside of the treatment, whether the abnormal reactions were treated and any other related information will be recorded in detail. Any medical conditions or diseases present prior to the start of the treatment will be considered abnormal reactions only if they worsen after starting the treatment.
Abnormal test values or results will be considered abnormal reactions only if they cause clinical symptoms, if they are considered clinically significant or if treatment is needed.
This study is a preliminary study targeting individuals with pre- or stage I hypertension, who will be randomly divided into treatment group A (2 times/week), treatment group B (3 times/week), and the control group (non-treated group). Basic analysis will be performed to assess the validity and safety of moxibustion for the treatment of pre- or stage I hypertension. The following results will be presented: the extent of stimulation provided by moxibustion, differences in the effect according to the frequency of treatment, and how long the efficacy of the treatment last. These results will be based on long-term follow-up observation.
This trial is currently recruiting participants.
KMS, JEP and KWK: Senior researcher of Medical Research Division, Korea Institute of Oriental Medicine.
SMC: Director of Medical Research Division, Korea Institute of Oriental Medicine.
YL, HJJ, SYJ and MHL: Researcher of Medical Research Division, Korea Institute of Oriental Medicine.
THY: Professor of the Department of Acupuncture & Moxibustion, Woosuk University.
Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
Randomized controlled trials
body mass index
heart rate variability
modified stress response inventory
Pittsburgh Sleep Quality Index
Fatigue Severity Scale
fasting blood sugar
liver function test
high sensitivity C-reactive protein
complete blood count
neck disability index
intent to treat
analysis of variance
- ABI index:
ankle brachial pressure index
- PWV index:
brachial-ankle pulse wave velocity.
This study was supported by the Korea Institute of Oriental Medicine(K12203).
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