Outcome Assessment
At the initial screening visit, the CRC will explain the study protocol to the patient. Then, the participants will be asked about their sociodemographic characteristics, including age, gender, occupation, past history, present illness, and medications, at an isolated room for allocation concealment. All adverse events will be recorded, and the practitioners will check the severity of the events and decide the continuance of the trial. Follow-up assessments will be performed once at 12 weeks after the initial screening visit (Table 1, Figure 1).
Primary outcome measurements
Blood pressure will be the primary outcome of this trial. The CRC will assess the participant’s blood pressure in a stable state using an automatic electronic blood pressure monitor (HBP-1300, OMRON DALIAN Co., Ltd., China). To obtain accurate data, the measurements will be conducted three times and their mean value will be used as the outcome. Blood pressure will be measured at baseline (assessment 1), prior to each of the visits (assessments 2 and 3), and during the follow-up visit (assessment 4). The primary endpoint is week 8 (assessment 3).
Secondary outcome measurements
Body composition is one of the secondary outcomes of this trial. The body composition test assesses the participant’s weight, body fat mass, body mass index, percentage of body fat, and weight-hip ratio. The participant will stand barefoot in the Inbody machine (Inbody 770; INBODY Co., Ltd., South Korea). After weight measurement, the participant will grasp the handles and the machine will pass multifrequency signals through the body to obtain the impedance value corresponding to each frequency. Using the measured impedance values, the machine will show the outcomes. The test will be conducted at baseline (assessment 1), week 8 (assessment 3), and at the follow-up visit (assessment 4).
Heart rate is the other secondary outcome of this trial. Participants will assess their heart rate in a stable state. Heart rate will be measured simultaneously with blood pressure; thus, measurements will be conducted at baseline (assessment 1), prior to each of the visits (assessments 2 and 3), and during the follow-up visit (assessment 4).
The strength and difficulty of the exercise is the other secondary outcome. The purpose of this survey is to compare the subjective strength of the exercise with absolute strength. The experimental group will be asked four questions. ① Was this exercise easy to follow? ② Was tai chi useful for improving your health? ③ Was the time at which tai chi was conducted appropriate? ④ Was the provided reference helpful for tai chi exercise? Participants will answer each question using a 0 to 10 category scale. They will rate the difficulty of tai chi exercise using the 0 to 10 visual analog scale (VAS) scale, on which VAS 0 indicates no difficulty, whereas VAS 10 indicates the maximum possible difficulty the person can imagine. Both surveys will be conducted once at the end of the exercise training; thus, the measurement point will be week 8 (assessment 3).
Sample size
This study referred to the results of a previous study (18) that used tai chi as the main evaluation index. The calculated sample size necessary for the t-test was 36 subjects in each group. The sample size calculation was conducted by G power analysis with an effect size of 0.67, test power of 0.80, and significance level of 0.05. Considering a dropout rate of 10%, we aim to recruit a total of 40 subjects in each group.
Statistical analysis plan
Continuous variables will be expressed as mean ± SD (standard deviation), and categorical variables will be expressed as n (%). The demographic baseline information will be tested using the Chi-squared test and independent t-test for age, gender, occupation, past history, present illness, and medications.
For primary outcome statistical analysis, the effectiveness of tai chi will be tested by calculating the differences in the degree of change in the maximum SBP and minimum DBP before and after treatment for each test subject. Comparisons of the differences before and after tai chi in the same group will be performed using the paired t-test, and differences between the experimental and control groups will be compared using an independent t-test. If the test results of the samples do not satisfy the normal criteria, they will be tested using a nonparametric test (a Wilcoxon signed-rank test or Wilcoxon rank-sum test) corresponding to the statistical technique.
Among the secondary evaluation variables, the heart rate and the results of the body composition analysis will be tested to verify the effectiveness of tai chi by calculating the difference between before and after the tai chi exercise in the same manner as described above. Another secondary measurement variable, the strength and difficulty of the exercise, will be evaluated through the researchers' observations, and the numerical value will be analyzed by a simple descriptive statistical method. We will perform a simple correlation analysis or simple regression analysis to determine whether there is a correlation between the differences in blood pressure changes and the strength and difficulty of the exercise perceived by the experimental group.
Information regarding adverse events will be collected through patient reports and researchers' observations, and the frequency of adverse events will be determined by the Chi-squared test or Fisher's Exact test. All statistical analyses will be conducted in a two-sided manner, with a significance level of 5%. In addition, when missing data are generated, last-observation-carried-forward (LOCF) and multiple imputation methods, which are widely used in clinical research, will be applied to process missing data and additional multiple imputation or regression analysis will be used to check the differences in results.
Safety
Because this is a simple exercise intervention study rather than a clinical study that applies untested drugs or medical devices, there is no possibility of adverse effects caused by general Korean medical treatment. However, in general, due to the interventional characteristic of exercise, simple muscular pain of the exercise site may occur. We will provide beverages such as bottled water or green tea during the exercise so that the subject can obtain water if necessary. In order to prevent falls and severe muscle aches, we will prepare a chair during exercise and provide a space to sit and relax according to the patient's physical strength. If a direct injury has occurred in connection with this study, appropriate medical action may be taken, as determined by the investigator of the clinical trial.
Data monitoring staff members of the clinical research service institution (Woosuk University) will periodically monitor the study by telephone, e-mail, or visits, if necessary. The monitoring staffs and researchers shall review the progress of the study and check all records of CRF. In addition, they will oversee whether the study is following the protocol finalized before the trial. In case a problem is identified, they will communicate with each other and modify the plan to solve the problem. If modifications of the protocol are required during the study, we will submit the modified protocol to the IRB. In case approval of a clinical trial or an alternation of the approved clinical trial is needed, the new plan or the changed plan with each clinical trial stage shall be submitted for approval by the clinical trial review committee. However, auditing and interim-analysis are not planned in our trial.
In accordance with government regulations and standards, all documents related to the conduct of clinical research must be kept by the director of clinical research, or the director of the institution and the clinical research manager, for three years after the completion of the clinical trial. However, the director of clinical research can change the preservation period and storage place in consultation with the clinical research manager.
Ethics and dissemination
As this clinical study was prepared with patient rights and well-being in mind based on the Helsinki Declaration, clinical research supervisors and staffs will analyze and understand the research plan accurately and actively respond to the problems of research participants.
Before participating in the clinical study, the researchers will explain all the details of the research, after which the research participants will be required to voluntarily agree to participate in the research. English initials of the names of participants in the trial will be recorded, and identifying information will be thoroughly managed through the Subject Identification Code List (SICD) to prevent personal information such as social security number from being leaked. Researchers and research organizations will be able to view the clinical research data at the time of reviews of the monitoring staff, inspections and IRB assessments, and government surveys. After completion of the research, the researcher will consult with the clinical research service institution (Woosuk University) to prepare a report of this study. The study findings will be disseminated in peer-reviewed journals and presented at national and international conferences. However, we are undecided whether to share the deidentified individual patient data (IPD).