Pilot Study Investigating the Effect of Tai Chi as Treatment for IBS-C
Phase: NA
Conditions: Irritable Bowel Syndrome With Constipation
Sponsor: Massachusetts General Hospital

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Pilot Study Investigating the Effect of Tai Chi as 
Treatment for IBS-C 
 
NCT: NCT04132804 
 
Principal/Overall Investigator: 
Kyle Staller, MD, MPH 
 
Funding: 
None 
 
Version Date: 
September 22, 2020 
 
 

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I. Background and Significance 
 
a.) Historical background 
 
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) 
characterized by abdominal pain and altered bowel habits. IBS is chronic and relapsing, causing 
significant reductions in health-related quality of life and work productivity.1 As the most 
commonly diagnosed gastrointestinal disorder, IBS affects between 4%-22% of the general 
population worldwide.2 In the United States, the distribution is approximately equal among IBS 
with constipation (IBS-C), IBS with diarrhea (IBS-D), and IBS with a mixed bowel pattern (IBS-
M).3 IBS is diagnosed in the absence of other medical causes with a pathogenesis mainly focused 
on abnormalities in gastrointestinal motility, visceral sensation, brain-gut interaction, and 
psychosocial distress.1 Therefore, treatment options for IBS are aimed at various action sites of the 
brain-gut axis through the use of pharmacotherapy and dietary/lifestyle changes. In the case of IBS-
C, strong methodological evidence for various types of conventional pharmacotherapy, such as 
bulking agents, prokinetics, and antispasmodics, is lacking.4 With inadequate relief from IBS 
symptoms, many patients seek out complementary and alternative medicine (CAM) therapies 
which are medical practices that are not considered to be a part of conventional medicine.5 A subset 
of CAM therapies focuses on mind-body interventions.6 In recognition of the communication 
between brain and gut, one such mind-body practice that may be beneficial for patients with IBS-C 
is the ancient practice of Tai Chi. 
Tai Chi Chuan (taijiquan) or Tai Chi is a mind-body practice borne of Chinese philosophy 
and martial arts which has been practiced for centuries to promote deep relaxation, strengthened 
health, and to prevent injuries and illness. The principle behind the practice is that Tai Chi 
improves the circulation of blood and Qi (energy) throughout the body which enhances the body’s 
natural healing capabilities. Tai Chi achieves this through gentle moving meditation and focusing 
on five building blocks: body, breath, mind, energy, and spirit. Through this method, Tai Chi 
practitioners exercise a balance between strength and flexibility, condition muscles, increase bone 
density, and massage their internal organs.7 
 
b.) Previous studies supporting the proposed research 
The practice of Tai Chi as a CAM therapy has already proven successful in the therapeutic 
arenas of other chronic conditions including anxiety, depression, PTSD, multiple sclerosis, 
fibromyalgia, rheumatoid arthritis, and osteoarthritis.8, 9, 10, 11, 12, 13 Tai Chi has even been shown to 
improve self-esteem, sleep quality, and immune response, and reduce declines related to aging and 
inactivity.14, 15, 16, 8 
In a recent randomized, controlled trial investigating the effect of Tai Chi compared to 
moderate aerobic exercise on symptoms associated with fibromyalgia, Tai Chi resulted in similar 
or greater improvement in symptoms than aerobic exercise. Fibromyalgia is a chronic condition 
characterized by musculoskeletal pain, fatigue, and sleep disturbance for which there is no cure. 
Although aerobic exercise is the most commonly prescribed non-pharmacological treatment for 
fibromyalgia patients, this study demonstrated that the mind-body approach of Tai Chi may be just 
as, if not more, effective in treating a complex pain condition.11 The findings from this study may 
have applications for the treatment of IBS-C, which is also a chronic condition with a primary 
symptom of pain. 

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While there have been some investigations of other mind-body modalities, such as 
meditation, hypnosis, and yoga, and their effect of IBS symptoms, Tai Chi as a mind-body 
intervention for the treatment of IBS-C has not yet been explored in scientific literature.17 Tai Chi 
differs from other mind-body therapies through the combination of gentle movements, meditation, 
and focus on flow of energy through the body. Both Tai Chi and Yoga philosophies involve 
meditation and movement in their practices, but the focus in Yoga is on asanas, or standing 
postures, and breathing with meditation. In comparison to stationary postures in Yoga, the gentle 
movements in Tai Chi have the effect of massaging internal organs. Another important difference 
between Yoga and Tai Chi is that Tai Chi emphasizes five building blocks: the body, breath, mind, 
energy, and spirit; whereas Yoga mainly concentrates on just three elements: the body, breath, and 
spirit.  With its specific focus on the mind and its relation to the body as well as the breath, energy, 
and spirit, Tai Chi may see different effects as a mind-body intervention for IBS compared to 
medication alone or Yoga. 
 
c.) Rationale behind the proposed research 
Through reinforcement of the mind-body connection, Tai Chi may be helpful in relieving 
chronic abdominal pain associated with IBS-C. The gentle moving meditation involved in Tai Chi 
practice may influence proper breathing and abdominal wall control in addition to massaging 
internal organs through movement. 
 
Previous research has suggested that therapies engaging the mind-body connection may 
have promising effects on functional bowel disorders in general, and on IBS specifically.18, 5 Some 
mind-body therapies, such as gut-focused hypnotherapy, have already gained approval as an 
effective treatment in reducing symptoms of IBS.19 Similarly to already established mind-body 
therapies, Tai Chi may positively impact symptoms of IBS-C by changing sensory perception or 
even calming colonic motility. Tai Chi practice could lead to reduced abdominal distention and 
improved anxiety and depression scores. 
 
II. Specific Aims 
 
 
This is a single center pilot study. The purpose of the study is to evaluate the efficacy of Tai 
Chi practice in reducing symptoms of IBS. Patients who meet the Rome IV criteria for IBS-C and 
who meet the inclusion criteria will be offered participation in the study. We hypothesize that 
patients practicing Tai Chi will have reduced symptoms of IBS-C as measured through the Global 
Assessment of Relief, Irritable Bowel Syndrome Severity Scoring System (IBS-SSS), Irritable 
Bowel Syndrome Quality of Life (IBS-QOL), Visual Analogue Pain Scale, and abdominal 
distention. We also hypothesize that daily entries made through the GeoPain app will show a trend 
toward reduced pain intensity. 
 
III. Subject Selection 
 
This study aims to recruit 24 total subjects to be enrolled at one site, Massachusetts General 
Hospital. The 24 subjects that this study aims to recruit factors in a dropout rate of 15%, with a 
final sample size of 20 subjects. 
 
 
INCLUSION/EXCLUSION CRITERIA: 

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Inclusion 
1. Age 18 – 70 years 
2. BMI ≤ 35 
3. Rome IV criteria for IBS-C 
4. Continued IBS-C throughout run-in period 
5. Compliant with reporting during run-in 
6. Ability to follow verbal and written instructions 
7. Ability to record daily patient reported outcomes via RedCap survey 
8. Ability to use the GeoPain app on a smart phone 
9. Ability to use Zoom as a platform for conducting study visits virtually 
10. Ability to respond to 80% of the daily diaries  
11. Ability to attend at least 7 out of 8 Tai Chi classes 
12. Informed consent form signed by the subjects 
 
Exclusion 
1. Unwilling to abstain from participation in Tai Chi (other than that provided for the study) or 
other mind-body practices (i.e. yoga that is new to regimen) until completion of the study 
2. Non-English speaking 
3. Participation in any other clinical trial with active intervention within the last 30 days 
4. Non-compliance with reporting during run-in period (less than 80% completed REDCap and 
GeoPain entries) 
5. Inability to stand without assistance for 20 minutes 
6. Patients reporting any usage of a prohibited medication during the run-in period 
7. History of regular opiate or narcotic pain-reliever use 
8. Current use of prescribed or illicit opioids 
9. Change in current medication regimen related to GI motility, laxatives, or antidepressants 
10. Abdominal pain severity of 4 on a 0-4 visual analogue scale, where 4 is the worst possible 
pain, during pre-screen or run-in 
11. Severe osteoarthritis 
12. Severe rheumatoid arthritis 
13. Severe constipation defined as <1 bowel movement per week without use of laxatives 
14. History of GI lumen surgery (including gastric bypass) at any time or other GI or abdominal 
operations within 60 days prior to entry into the study 
15. History of small bowel resection (except if related to appendectomy) 
16. Subjects anticipating surgical intervention during the study 
17. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit 
18. Crohn’s disease or ulcerative colitis 
19. History of intestinal stricture (e.g., Crohn’s disease) 
20. BMI >35 
21. Pregnancy (or positive urine pregnancy test(s) in females of childbearing potential) 
22. Known history of diabetes (type 1 or 2) 
23. History of gastroparesis 
24. History of abdominal radiation treatment 
25. History of pancreatitis 
26. History of malabsorption or celiac disease 
27. History of intestinal obstruction or subjects at high risk of intestinal obstruction including 

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suspected small bowel adhesions 
28. History of human immunodeficiency virus 
29. History of cancer within the past 5 years (except adequately-treated localized basal cell skin 
cancer or in situ uterine cervical cancer) 
30. Neurological disorders, metabolic disorders, or other significant disease that would impair 
their ability to participate in the study 
31. Any other clinically significant disease interfering with the assessments according to the 
Investigator (e.g., disease requiring corrective treatment, potentially leading to study 
discontinuation) 
32. Any relevant biochemical abnormality interfering with the assessments according to the 
Investigator 
33. Inability to attend at least 7 out of the 8 Tai Chi classes 
34. Inability to respond to 80% of the daily diaries 
 
a.) Source of subjects and recruitment process 
Subjects will be recruited from the MGH Gastroenterology Unit based on the enrollment 
criteria. GI physicians at MGH will be informed of the study and can refer patients if they are 
deemed appropriate for the study. Study staff will review subject’s electronic medical records to 
confirm inclusion and exclusion criteria. Additionally, electronic medical records of potential 
subjects coming into the GI clinic for an appointment will be screened in order to identify eligible 
patients with IBS. When an eligible patient is identified, their provider will be contacted in order to 
confirm the patient’s eligibility as well as to gain permission to contact the patient. The treating 
physician/investigator will first present the study to the subject during a clinic visit. If the subject is 
interested in the study, the subject will be approached by one of the licensed physician 
investigators listed on the protocol or the study coordinator to obtain consent. If treating physicians 
are approaching their own patients, consent will be obtained by a study coordinator to avoid any 
coercion. All patients will be explicitly told that their decision to enroll in the study will have no 
bearing on their current or future treatment and this statement will be mandated as part of the 
protocol. 
Subjects may also be identified using the Research Patient Data Registry (RPDR) system. 
Electronic medical records of potential subjects will be reviewed to confirm inclusion and 
exclusion criteria. The patient’s provider will be contacted to confirm the patient’s eligibility as 
well as to gain permission to contact the patient. The recruitment letter by the PI and the patient’s 
provider will be sent. Patients who agreed to direct contact (RODY YES) will receive a recruitment 
letter from the PI. If the patient does not contact the study coordinator within 1 week, they will be 
contacted by phone and/or email by the study coordinator. All subjects will undergo telephone 
prescreening by the study staff. 
In addition to patients of MGH, subjects from the general greater Boston population will 
also be recruited. Subjects from the general population will be recruited through the Partners 
Clinical Trials system. Through this service, interested respondents may provide their contact 
information to be contacted by research study staff. Due to COVID-19 restrictions, social 
distancing, and the conduct of the study entirely remotely, subjects who reside outside the state of 
Massachusetts who reach out to the study staff may also be recruited for the study and screened for 
eligibility.  
Subjects from the larger population of Facebook and/or Instagram will be also be recruited. 
A Facebook page, that is specific to this research study will be published and will provide links to 

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both the Partners Rally website and a REDCap pre-screening survey, both of which will be used by 
study staff to contact patients by phone or email (Send Secure) for administration of the phone 
screening. A Facebook ad will be created and published onto the MGH Tai Chi Study Facebook 
page for potential participants to view and access Rally or the REDCap survey. Security settings 
will be put into place to ensure that no posts will be allowed on this page or the ads, it will only be 
used to provide the links to interested participants who will then agree to be contacted by study 
staff. 
 
 
IV. Subject Enrollment 
 
a.) Methods of enrollment 
1. Patients may be approached by a licensed physician investigator listed on the protocol 
or a research coordinator in the GI clinics if they have a history of IBS and agree to hear 
more about the trial. 
2. After receiving approval from a patient’s physician, patients may be contacted by the 
research coordinator prior to their appointment and asked if they would like to hear 
more about the trial. 
3. Any patients agreeing to hear more about the trial will learn more before beginning the 
informed consent process should they agree to participate as well as determining 
whether they meet all of the inclusion criteria. 
4. Patients may be contacted about the research study by their MGH physician on behalf 
of the research team. Afterward, patients may then be contacted by the research team 
directly. 
5. Subjects who have provided their contact information through the Partners Clinical 
Trials system may be contacted by the research team directly. 
 
b.) Procedures for obtaining informed consent 
1. Patients agreeing to participate will sign an informed consent with the study physician 
or research coordinator at the time of enrollment, after proper informed consent has 
been provided by the site. Due to COVID-19 restrictions and social distancing, 
REDCap eConsent will take the place of written documentation of informed consent.  
 
c.) Treatment Assignment 
1. All patients will participate in 8 weeks of one-hour Tai Chi sessions once per week. 
 
V. Study Procedures 
 
a) Remote conduct of study visits and procedures 
 
Due to COVID-19 and its restrictions, all eligibility screening and study visits listed below 
will be performed remotely until restrictions are lifted at the study site. All remote visits will be 
conducted over Zoom and the visit schedule will not change. All research staff will follow the 
MGH requirements for using Zoom (Enterprise Zoom as well as Healthcare Zoom- for any study 
visits involving patient care.) All questionnaires will be administered remotely via REDCap or over 
the phone. All Zoom link invites will be password protected and emailed by research staff to study 
participants using Send Secure or unencrypted email, depending on the subject’s preference.  

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b.) Study visits and parameters to be measured 
1. Eligibility Screen (to be conducted via Healthcare Zoom) 
a. Obtain informed consent (performed by research staff) 
b. Collect demographic data (performed by research staff) 
c. Assessment of sufficient space to perform Tai Chi in-home (performed by 
research staff) 
d. Assess inclusion/exclusion criteria (performed by research staff) 
e. Rome IV questionnaire to screen for IBS-C (performed by research staff) 
f. Collect medical and surgical history (performed by research staff) 
g. Collect concomitant medications (performed by research staff) 
h. Self report of height, weight, and waist measurement (if restrictions are lifted 
and study visits are being performed on site, vital signs will be recorded) 
(performed by research staff) 
i. Perform brief physical examination by study physician 
j. Visual Analogue Pain Scale (performed by research staff) 
k. Questionnaires including Global Assessment of Relief, Hospital Anxiety and 
Depression Scale (HADS), Gastrointestinal Symptom Rating Scale-IBS version 
(GSRS-IBS), Irritable Bowel Syndrome-Behavioral Responses Questionnaire 
(IBS-BRQ), Fear of Food Questionnaire (FFQ), Visceral Sensitivity Index 
(VSI), IBS-SSS, and IBS-QOL(performed by research staff) 
l. Record whether study participant verbally states they are pregnant or not for 
women of child-bearing potential (If restrictions are lifted and study visits are 
being performed on site, perform urine pregnancy test on women of child-
bearing potential) (performed by research staff) 
m. Self-reported leg strength assessment 
 
2. Run-In Period 
After a screening visit in which patient eligibility will be determined through use of the 
Rome IV IBS-C criteria along with other inclusion and exclusion criteria as above, there 
will be a 2-week run-in period. The 2-week run-in period may occur up to 3 months 
before the trial start date to facilitate accumulation of enough patients for a 10-person 
class. 
 
Prohibited Medications 
During this time no use of contraindicated medication per exclusion criteria will be 
allowed. 
a. Opiate and narcotic pain-relievers 
 
Permitted Medications at Stable Doses 
The following medications are permitted as long as the medication dose has been stable 
for 3 months prior to the run-in period: 
a. Laxatives (e.g. linaclotide, lubiprostone, bisacodyl, senna, MiraLAX) 
b. Prokinetic medications (e.g. domperidone, metoclopramide, erythromycin, 
prucalopride) 
c. Antidepressant medications (e.g. SSRIs, SNRIs, TCAs, trazodone, bupropion) 
d. Neuromodulators (e.g. gabapentin, pregabalin, buspirone) 

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e. Aluminum/Magnesium 
f. Calcium-channel blockers (e.g. amlodipine, diltiazem, nifedipine, nicardipine) 
 
During the run-in period, subjects will be asked to complete a daily REDCap diary 
entry, a daily GeoPain entry, as well as complete the Visual Analogue Pain Scale, and 
turn in a stool sample within 2 weeks before the start of the treatment period. A stool kit 
may be mailed to subjects’ homes, which subjects will then mail completed back to the 
research site. 
 
Rescue Medications 
If a subject does not have any documented bowel movement for 5 consecutive days and 
is in need of a rescue treatment, they will be asked to please contact the study doctor or 
study coordinator immediately. The study doctor will recommend the following rescue 
treatments, as applicable, in the following order: 
a. Laxatives: either MiraLAX or Dulcolax 
b. Glycerin suppository 
c. Enema 
 
Administration of the rescue treatment will be at the discretion of the investigator based 
on their assessment of the subject’s symptoms; administration of rescue treatment will 
be monitored and recorded. 
 
3. Treatment Period (Day 0 to 49) 
One day prior to the treatment period, subjects will again complete the Rome IV 
questionnaire confirming that inclusion and exclusion criteria continue to be satisfied. 
 
Subjects will be asked to refrain from making any major lifestyle changes (e.g. starting a 
new diet or changing their exercise pattern outside of Tai Chi practice) during the study. 
 
During the treatment period, subjects will meet via Zoom once per week for one-hour Tai 
Chi lessons with an experienced instructor. A member of the research staff will send the 
password-protected Zoom invitation link to the subject’s preferred email address via Send 
Secure or regular email, depending on the subject’s preference. Subjects will also be 
instructed to practice Tai Chi at home outside of the lessons using the instructions, 
handouts, and guidance from the instructor. 
 
Subjects will be instructed to complete a daily REDCap diary entry and a daily GeoPain 
entry to record information about stool frequency and consistency, abdominal bloating, 
abdominal discomfort, and abdominal pain. Subjects will also use the REDCap diary to 
report rescue medication use and daily Tai Chi practice. 
 
The lessons will occur on Days 0, 7, 14, 21, 28, 35, 42, and 49. The Tai Chi lessons will 
take place remotely via Zoom. Should restrictions be lifted and study visits be performed on 
site, lessons will take place in the Simches Research Center at 185 Cambridge Street. 
 
On Days 0, 21, and 49 subjects will be phoned by a member of the research staff for 

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assessments prior to their regularly scheduled Tai Chi lesson. Assessments will include 
vitals (if the study is operating on site only), weight, height, waist circumference, leg 
strength, and questionnaires. Assessments will be completed with research staff over the 
phone or, if restrictions are lifted and study visits are conducted on site, at the Center for 
Neurointestinal Healthcare at 165 Cambridge Street, after which subjects will go to their 
regularly scheduled Tai Chi lesson at Simches. Participants will also complete a qualitative 
survey over the phone with a member of the study staff that will be audio recorded and later 
transcribed in order to gain a full, complete, qualitative understanding of the patient’s 
perspective of the investigational treatment that was used. 
 
4. Post-Treatment Period (Day 77) 
Subjects will complete a REDCap diary entry regarding symptoms 28 days post-
treatment, 4 weeks after the final study visit.   
 
5. Schedule of Events 
Study Procedures 
Screening 
Run-In (Up 
to 3 
months 
prior to 
Treatment) 
Treatment 
Post-
Treatment 
Visit 
Visit 1 (Up 
to 3 
months 
prior to 
treatment) 
Visit 2 
(Day 
0) 
Visit 3 
(Day 7) 
Visit 4 
(Day 
14)  
Visit 5 
(Day 
21) 
Visit 6 
(Day 
28) 
Visit 7 
(Day 
35) 
Visit 
8 
(Day 
42) 
Visit 
9 
(Day 
49) 
4 Weeks 
Post- 
Treatment 
(Day 77) 
Informed Consent 
X 
  
  
  
  
  
  
  
  
  
 
Inclusion/exclusion 
criteria 
X 
  
  
  
  
  
  
  
  
  
 
Demographics, medical 
history, and 
medication history 
X 
  
  
  
  
  
  
  
  
  
 
Concurrent medical 
conditions and 
concomitant 
medications 
X 
  
X 
  
  
X 
  
  
  
X 
X 
Physical examination 
X 
  
  
  
  
  
  
  
  
  
  
Vital signs 
X 
  
X 
  
  
X 
  
  
  
X 
X 
Weight, height, waist 
circumference (a) 
X 
  
X 
  
  
X 
  
  
  
X 
X 
Pregnancy test 
X 
  
  
  
  
  
  
  
  
  
  
Tai Chi Lessons 
  
  
X 
X 
X 
X 
X 
X 
X 
X 
 
Stool Sample 
X 
  
  
  
  
  
  
  
  
X 
X 
Daily Diary 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GeoPain Reporting 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Global Assessment of 
Relief 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
HADS 
X 
  
X 
  
  
X 
  
  
  
X 
X 
VSI 
X 
  
X 
  
  
X 
  
  
  
X 
X 
Visual Analogue Pain 
Scale 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 

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(a) Weight, height, and waist circumference are measured and BMI is calculated at initial screening visit only. Weight 
and waist circumference only is measured at subsequent visits. 
 
 
 
6. Investigational Treatment to be Used 
Subjects will practice Tai Chi via Zoom (if on site, at the Simches Research Center.) We 
will use a standardized Tai Chi protocol derived from previously tested trials10,11,12,13. The 
Tai Chi program will be based upon the classical Yang Tai Chi philosophy which includes 
108 postures show to be a moderate intensity exercise. 
 
In the first session, the Tai Chi instructor will explain the program, exercise theory, and 
procedures of Tai Chi. The patients will be provided with printed materials on the Tai Chi 
Mind-Body program including Tai Chi principles, practicing techniques, and safety 
precautions. Subjects will then begin Tai Chi practice under the instruction of the Tai Chi 
instructor. The Tai Chi instructor will have extensive experience (>20 years) conducting Tai 
Chi mind-body programs and will be following a Tai Chi protocol specifically designed for 
individuals with IBS-C. 
 
Every session will include the following components: (1) Tai Chi warm ups with a strong 
emphasis on balance between strength and flexibility while reviewing Tai Chi principles; 
(2) Tai Chi breathing with self-massage (3) Tai Chi relaxation with meditation and 
visualizations (4) Tai Chi form which includes 10 moves from the Yang style Tai Chi (5) 
Tai Chi drills which are the Tai Chi individual postures practice (6) Tai Chi combination of 
movements and principles which are part of the Tai Chi philosophy. We will instruct 
patients to practice at least 30 minutes a day at home throughout the intervention period. 
 
7. Data to be Collected and Timeline for Collection 
a. Primary endpoints 
1. IBS-SSS (pre-treatment, halfway point, and at conclusion of study) 
Rome IV Questionnaire 
X 
  
 
  
  
  
  
  
  
  
  
IBS-SSS 
X 
  
X 
  
  
X 
  
  
  
X 
X 
IBS-QOL 
X 
  
X 
  
  
X 
  
  
  
X 
X 
GSRS-IBS 
X 
 
X 
 
 
 
 
 
 
X 
X 
IBS-BRQ 
X 
 
X 
 
 
 
 
 
 
X 
X 
Fear of Food 
Questionnaire 
X 
 
X 
 
 
 
 
 
 
X 
X 
Leg strength 
Assessment 
X 
 
X 
 
 
X 
 
 
 
X 
X 
Treatment Satisfaction 
  
  
  
  
  
  
  
  
  
X 
X 
Pre-treatment AE 
Assessment 
X 
X 
  
  
  
  
  
  
  
  
  
AE Assessment 
X 
  
X 
  
  
X 
  
  
  
X 
X 
Qualitative Post-Tx 
Survey 
 
 
 
 
 
 
 
 
 
X 
 
CSQ 
 
 
 
 
 
 
 
 
 
X 
 
Instructor Assessment 
  
  
  
  
  
  
  
  
  
X 
X 

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b. Secondary endpoints 
1. Likelihood of continuing treatment (5-point scale, end of study) 
2. Treatment satisfaction (5-point scale, end of study) 
3. Global Assessment of Relief and Visual Analogue Pain Scale (pre-treatment and 
each study visit) 
4. Change of IBS-QOL, VSI, and HADS (pre-treatment, halfway point, and at 
conclusion of study) 
5. For each BM: Bristol stool scale, stool frequency (CSBMs and SBMs; for each 
BM, during run-in and during study) 
6. Waist circumference measurements (pre-treatment, halfway point, and at 
conclusion of study) 
7. Daily: Bloating Scale, Abdominal Discomfort Scale, Constipation Severity 
Scale 
8. Gastrointestinal Symptom Rating Scale-IBS version (GSRS-IBS), Irritable 
Bowel Syndrome-Behavioral Responses Questionnaire (IBS-BRQ), Fear of 
Food Questionnaire (FFQ) (pre treatment, study visit 2, and at conclusion of 
study) 
9.  Leg strength assessment patient (pre-treatment, halfway point, and at 
conclusion of study) 
10. Instructor assessment as to confidence that patient has mastered technique (x1 at 
end of study, 5-point scale) 
11. Client satisfaction questionnaire and qualitative survey (at conclusion of study) 
12. Stool for metabolomics, and microbiome (pre-treatment and at conclusion of 
study) 
 
8. Compliance 
a. Study coordinator will remind subjects of Tai Chi sessions and monitor completion 
of daily diaries, reports of home practice, and rescue medication use. Subject 
attendance will be monitored during each Zoom/in-person session by staff-
completed attendance forms as well as class sign-in sheets. Number of missed 
sessions for each subject will be tracked. 
b. During Run-in Period, subjects must complete 80% of REDCap and GeoPain entries 
to be considered compliant with reporting and to remain eligible to participate in the 
study. 
 
b.) Adverse Events 
1. Definition of adverse events 
a. An adverse event (AE) is any untoward medical occurrence (sign, symptom, illness, 
abnormal laboratory value, or other medical event) in a subject, whether or not 
related to the investigational medical device. This includes events related to the 
procedures involved (any procedure in the Clinical Investigation Plan). 
 
2. A serious adverse event (SAE) is any AE that: 
a. Led to death 
b. Resulted in a life-threatening condition 
c. Resulted in a permanent impairment of a body structure or a body function 
d. Required inpatient hospitalization or prolongation of existing hospitalization for ≥ 

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24 h (elective hospitalizations and/or hospitalizations for treatment of pre-existing 
conditions that did not worsen from baseline are not considered AEs and should not 
be reported as SAEs) 
e. Resulted in a medical or surgical intervention to prevent permanent impairment to a 
body structure or a body function 
f. Led to fetal distress, fetal death or a congenital abnormality, or birth defect 
 
3. Adverse event recording, assessment, and reporting procedure 
a. All AEs regardless of seriousness or relationship to treatment including those 
occurring during the screening period (after the signature of the Informed Consent 
Form) are to be recorded in the appropriate electronic CRF. 
b. AEs reported by subject will be discussed in detail and recorded by the Investigator 
at each visit. AEs will be collected until 28 days after the last administration of the 
investigational treatment (i.e., until subject terminates his/her participation in the 
study). 
c. The Investigator should specify the date of onset, severity, action taken with respect 
to the investigational treatment, corrective treatment, outcome, and whether or not 
there is a reasonable possibility that the AE may have been caused by the 
investigational treatment. 
d. Should an AE be reported by a study participant that resides/is located outside the 
state of Massachusetts and that is determined to have been caused by the 
investigational treatment, the Investigator will contact the participant’s local 
providers to assess the need for follow-up.  
e. AEs are graded as follows: 
1. Mild: sign or symptom, usually transient, requiring no special treatment and 
generally not interfering with usual activities. 
2. Moderate: sign or symptom, which may be ameliorated by simple therapeutic 
measures, may interfere with usual activity. 
3. Severe: sign or symptom intense or debilitating and interfering with usual 
activities without being immediately life-threatening. Recovery is usually aided 
by therapeutic measures. 
4. Very Severe: sign or symptom life-threatening. Urgent intervention indicated. 
f. The assessment of the relationship of an AE to the investigational treatment is a 
clinical decision based on all available information at the time of the completion of 
the electronic CRF: 
1. Most probably related: follows a reasonable temporal sequence from treatment 
use and cannot be reasonably explained by known characteristics of the subject’s 
clinical data. 
2. Possibly related: follows a reasonable temporal sequence from treatment use but 
could have been produced by the subject’s clinical state regardless of the 
medical device. 
3. Probably not related: temporal association is such that the treatment use is not 
likely to have had any reasonable association with the observed event. 
4. Not related: no relationship to the use of the treatment is perceived. 
g. Abnormalities of vital signs and laboratory results are to be recorded as AEs only if 
they are considered by the Investigator as clinically significant (symptomatic, 
requiring corrective treatment, leading to discontinuation, or fulfilling a seriousness 

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criteria). 
h. Any pre-existing conditions or signs and/or symptoms present in a subject prior to 
the Screening Visit should be recorded as medical/surgical history. 
i. In this study, the following events will be reported to the authorities on expedited 
basis: 
1. All SAEs will be expeditiously reported to the relevant Regulatory Authorities 
and the Ethics Committees. 
 
4. Anticipated adverse treatment effects 
a. No adverse treatment effects are anticipated. 
 
5. Pregnancy 
a. In case of pregnancy, the investigational treatment will be discontinued. 
 
 
VI. Sample Processing 
 
a.) Stool 
Upon receiving the samples, stool will be centrifuged and separated from the fixative. Samples 
will then be aliquoted and stored at -80oC before microbiome analysis. The sample in the ethanol 
solution will be stored in -80oC without removing the solution. 
1. Metabalomics 
Stool will be stored to check for metabalomics that may profile changes between the 
pre-treatment and treatment sample. 
2. Microbiome Analysis 
Standard 16s rRNA sequencing for taxonomic identification and metagenomic profiling 
of the gut microbiome will be performed on stool samples to profile microbiome 
diversity and changes in microbiome between the pre-treatment and treatment sample. 
 
VII. Biostatistical Analysis 
 
a.) Endpoint analyses 
1. Primary endpoint: IBS-SSS will be compared in a paired fashion for individual patients 
before and after the intervention using repeated measures t-test. 
2. Secondary endpoints: The secondary endpoints (as outlined in section V.a.6.b.) will be 
compared in a similar fashion. 
 
b.) Power analysis 
This is a single-center clinical exploratory pilot investigating the treatment of IBS-C using 
Tai Chi. As a pilot study, we hope to enroll 24 subjects with a final sample size of 20 subjects. The 
study will be conducted in two cycles of at least 10 subjects each to facilitate a full classroom size. 
Based on a previous pilot study involving Tai Chi as treatment for rheumatoid arthritis12, 20 
subjects appears to be a feasible number for detecting a trend toward outcomes that can be 
investigated in a future larger clinical trial. 
 
VIII. Risks and Discomforts 

Page 14 of 18 
 
 
 
a.) Tai Chi 
Tai Chi is a relatively safe practice that is unlikely to cause injury if done with proper 
instruction. Caution should be exercised with conditions such as pregnancy, hernia, joint problems, 
and severe osteoporosis. 
 
b.) Other Possible Risks 
Other possible risks and side effects include skin irritation from inadvertently coming in 
contact with preservatives in the specimen collection materials, breach of confidentiality involving 
protected health information, and that information about taking part in a metabolic/microbiome 
study could influence insurance companies or employers regarding the patient’s health. Study IDs 
will be utilized to minimize breaches of confidentiality. Filling out questionnaires could cause 
patients to feel uncomfortable. 
 
IX. Potential Benefits 
 
a.) It is hypothesized that Tai Chi may be of benefit in patients with IBS-C. Potential benefits may 
include a decrease in self-reported abdominal pain/discomfort, straining, bloating, and constipation 
severity, as well as improved quality of life and symptoms severity. 
 
b.) All subjects will be provided with free parking stickers for each visit and $50 upon completion 
of Days 0, 21, and 49 (Visit 2, 5, and 9). 
 
X. Monitoring and Quality Assurance 
 
a.) Good clinical practice 
The investigator will ensure that this study is conducted in accordance with the principles of 
“Good Clinical Practice”, as outlined in Title 21 of Code of Federal Regulations (CFR), Part 312, 
subpart D, “Responsibilities of Sponsors and Investigators”; 21 CFR, part 50, “Protection of 
Human Subjects”; 21 CFR, part 54, “Financial Disclosure by Clinical Investigators”; 21 CFR, part 
56, “Institutional Review Boards”; and 21 CFR, Part 11,“Electronic Records, Electronic 
Signature”, are adhered to. 
 
b.) Institutional review board (IRB) approval 
The protocol and any accompanying material to be provided to the patient (such as 
advertisements, patient information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the investigator to the MGH IRB. Approval from the IRB must be 
obtained before starting the study and should be documented in a letter to the investigator 
specifying the protocol number, protocol version, protocol date, documents reviewed, and date on 
which the committee met and granted approval. Any modifications made to the protocol after 
receipt of IRB approval must also be submitted to the IRB for approval before implementation. 
 
c.) Informed consent 
Due to COVID-19 restrictions and social distancing, consent will be obtained remotely 
using REDCap eConsent/Paperless consent in place of written informed consent, in accordance 
with 21 CFR Part 11. The eConsent is equivalent to written consent. The Partners approved 

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REDCap eConsent template will be used to deliver the approved consent form and obtain an 
electronic signature from study participants and the principal investigator. All electronic consent 
documents will be stored in the subject’s research record in a password protected, Partners 
encrypted/secured device. 
Written informed consent, in accordance with 21 CFR Part 50, must be obtained prior to 
participation in the study when social distancing restrictions are lifted and the study is operating on 
site. Within the context of the inclusion criteria, a proportion of eligible patients may be exhibiting 
significant cognitive impairment and the lack of capacity to provide consent. As such, all patients 
will require surrogate consent by a legally authorized representative. The investigator or staff will 
determine the appropriate family member-person to contact regarding the study, based on the 
standard operating procedures of MGH and local and state laws. The signed consent form must 
remain in the patient’s medical chart and must be available for verification at any time. 
 
d.) Liability and insurance 
The civil liability of the investigator, the persons instructed by the investigator and the 
hospital, practice, or institute in which they are employed, and the liability of the financial loss due 
to personal injury and other damage which may arise as a result of the carrying out of this study are 
governed by the terms and conditions set forth in the Clinical Trial Agreement and applicable law. 
 
e.) Documentation of study findings 
Required information will be entered into the appropriate CRFs. All CRFs are to be 
completed accurately and promptly and should be updated as needed so they reflect the latest 
information on the patient’s file. All records are to be kept in conformance with applicable 
guidelines and SOPs. When the study is completed, the investigator must retain the essential 
documents for as long as needed to comply with regulatory authority, local regulations and sponsor 
requirements further detailed in Section 10.2.5. The investigator shall notify the sponsor prior to 
moving or destroying any of the study documents. 
 
f.) Study monitoring 
1. For Investigator-Initiated Research Studies, Investigators are responsible for ensuring 
proper monitoring of the investigation. The Investigator’s assigned clinical monitors are 
responsible for inspecting the CRFs throughout the study to verify adherence to the 
protocol; completeness, accuracy, and consistency of data; and adherence to GCPs. The 
monitors should have access to patient medical records and other study-related records 
needed to verify entries on the CRFs. In accordance to ICH Good Clinical Practice 
(ICH/GCP) guidelines, the Investigator’s assigned clinical monitors must have direct access 
to the investigator’s source documentation in order to verify the data recorded in the CRFs 
for consistency. 
2. The monitor is responsible for routine review of the eCRFs at regular interval throughout 
the study to verify adherence to the protocol and the completeness, consistency, and 
accuracy of the data being entered on them. The monitor should have access to any patient 
records needed to verify the entries on the CRFs. The investigator agrees to cooperate with 
the monitor to ensure that any problems detected in the course of these monitoring visits are 
resolved. 
 
g.) Access to Information for Auditing or Inspections 

Page 16 of 18 
 
 
Representatives of regulatory authorities, IRB, or of the Sponsor may conduct inspections 
or audits of this clinical study. If the investigator is notified of an inspection by a regulatory 
authority the investigator agrees to notify the Sponsor immediately. The investigator agrees to 
provide to representatives of a regulatory agency, IRB or IEC, or Sponsor access to source 
documents/records, facilities, and personnel for the effective conduct of any inspection or audit. 
 
h.) Data quality assurance 
Data will be entered into a secure and validated database using eCRFs. Data entered may be 
checked at the point of entry and through external validation checks for accuracy. After resolution 
of any discrepancies and automated data-review procedures, the final data sets will be subject to a 
quality assurance audit. When the database is declared to be complete and accurate, it will be 
locked. Any changes to the database after that time can only be made by written notice. The 
investigator will be responsible for ensuring the accuracy, completeness, and timeliness of the data 
reported to the sponsor in the CRFs and in all required reports. Data reported on the CRFs, which 
are derived from source documents, should be consistent with source documents or the 
discrepancies should be explained. To ensure the quality of the clinical data across all participants 
and sites, a clinical data management review will be performed on all patient data. During this 
review, patient data will be checked for consistency, omissions, and any apparent discrepancies. In 
addition, the data will be reviewed for adherence to protocol and GCPs. To resolve any questions 
arising from the clinical data-review process, data queries will be sent for the site to complete. The 
principal investigator will electronically sign and date the indicated places on the CRF. This 
signature will indicate that the principal investigator inspected or reviewed the data on the CRF and 
the data queries, and that the investigator agreed with the content. 
 
i.) Study Files and Retention of Records 
1. The investigator must maintain adequate and accurate records to fully document the 
conduct of the study and to ensure that study data is subsequently verified. These 
documents should be classified into two separate categories: (1) investigator’s study file, 
and (2) patient clinical source documents. The investigator’s study file will contain the 
protocol/amendments, printed (or electronically archived) copies of the patient CRFs, IRB, 
and governmental approval with correspondence, informed consent, drug accountability 
(receipt/dispensing) records, staff curriculum vitae and authorization forms, information 
regarding monitoring activities, investigator correspondence, and other appropriate 
documents and correspondence. 
2. Patient clinical source documents for this study would include, but are not limited to, the 
following: 
a. Patient identification (name, date of birth, gender) 
b. Documentation that patient meets eligibility criteria, i.e., relevant medical history, 
physical examination, and confirmation of diagnosis 
c. Dated notes of the day of entry into the study including study number, patient 
identification number, verification that the trial was discussed and written informed 
consent was obtained 
d. Dated notes for each protocol assessment and documentation that protocol specific 
procedures were performed 
e. Documentation of all adverse events, including any action taken with regard to 
study intervention and outcome 

Page 17 of 18 
 
 
f. Concomitant medications (including start and end date, dose if relevant) 
g. Date of trial completion and reason for early discontinuation, if applicable 
 
j). Confidentiality 
The investigator must ensure that all participants’ confidentiality will be strictly maintained 
and that their identities are protected from unauthorized parties. Only patient initials, date of birth, 
and an identification code (i.e., not names) should be recorded on any form or biological sample 
submitted to the sponsor, IRB, or laboratory. The investigator must keep a screening log showing 
codes, names and addresses for all patients screened and for all patients enrolled in the trial. On 
CRFs or other documents that are submitted to the sponsor, participants should be identified by an 
identification code and not by their names. 
 
k.) Protocol and Protocol Amendments 
1. The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. No amendments will be permitted to 
this protocol or to the conduct of the study without approval from the IRB. These 
communications will be documented in writing. 
2. All protocol amendments must be submitted to the IRB in accordance with local 
requirements. Approval must be obtained before changes are implemented. 
 
 
XI. References 
 
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Bowel Syndrome: A Meta-analysis. Clinical Gastroenterology and Hepatology, 10(7), 712-
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3. Guilera, M., Balboa, A., & Mearin, F. (2005). Bowel Habit Subtypes and Temporal Patterns 
in Irritable Bowel Syndrome: Systematic Review. The American Journal of 
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4. Lesbros-Pantoflickova, D., Michetti, P., Fried, M., Beglinger, C., & Blum, A. L. (2004). 
Meta-analysis: the treatment of irritable bowel syndrome. Alimentary Pharmacology and 
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5. Hussain, Z., & Quigley, E. M. M. (2006). Systematic review: complementary and 
alternative medicine in the irritable bowel syndrome. Alimentary Pharmacology and 
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6. Shen, Y.-H. A., & Nahas, R. (2009). Complementary and alternative medicine for treatment 
of irritable bowel syndrome. Canadian Family Physician Medecin De Famille Canadien, 
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7. Rones, R., & Silver, D. (2007). Sunrise tai chi: simplified tai chi for health & longevity. 
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