Therapeutic effects and safety of Chinese herbal formula Tongxie Yaofang versus placebo for diarrhea-predominant irritable bowel syndrome

ISRCTN	ISRCTN12453166
DOI	https://doi.org/10.1186/ISRCTN12453166
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	National Natural Science Foundation of China
Funder	National Natural Science Foundation of China (No. 81830115)

Submission date: 22/03/2021
Registration date: 23/03/2021
Last edited: 28/01/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Irritable Bowel Syndrome (IBS) is a bowel disease that causes abdominal pain associated with bowel movements or changes in bowel habits. IBS can be categorized into four subtypes, diarrhea-predominant irritable bowel syndrome (IBS-D) is one of them and accounts for about 40% of all IBS patients. IBS-D significantly reduces the quality of life of patients and affects the patient's daily activities. No specific therapeutic drugs have been found. Chinese herbal formula Tongxie Yaofang was first recorded in the Dan Xi Xin Fa. It belongs to the formulation of Chinese medicine and consists of four Chinese herbal medicine: Baizhu, Baishao, Chenpi and Fangfeng. Some previous clinical studies have reported that Tongxie Yaofang has potential benefits in the treatment of IBS, but the quality of these studies is not high. The aim of this study is to evaluate the effects and safety of Tongxie Yaofang in the treatment of IBS-D.

Who can participate?
Patients aged 18 to 65 years with diarrhea-predominant irritable bowel syndrome

What does the study involve?
Participants are randomly allocated into two groups. One group receives Tongxie Yaofang for 8 weeks, and the control group receives a placebo (dummy drug) of Tongxie Yaofang for 8 weeks. The dosage given is 3.7 g of granules two times per day. The patients will be followed up for 3 months after the treatment to assess IBS symptom severity.

What are the possible benefits and risks of participating?
If successful, the medication has the potential to preserve and enhance the benefits of rehabilitation for patients with diarrhea-predominant irritable bowel syndrome. This may reduce hospital admissions and improve the patient’s quality of life.
The tested medication may cause adverse events during the treatment.

Where is the study run from?
Fangshan Hospital of Beijing University of Chinese Medicine, Beijing (China)

When is the study starting and how long is it expected to run for?
July 2020 to December 2022

Who is funding the study?
National Natural Science Foundation (China)

Who is the main contact?
1. Jian-ping Liu (scientific)
Liujp@bucm.edu.cn
2. Hong-Jie Cheng (clinical)
chenghongjie1971@163.com

Contact information

Prof Jian-ping Liu
Scientific

11 Bei San Huan Dong Lu
Chaoyang District
Beijing
100029
China

Phone	+86 (0)10 64286760
Email	Liujp@bucm.edu.cn

Prof Hong-Jie Cheng
Public

Fangshan Hospital of Beijing University of Chinese Medicine
Fangshan District
Beijing
102400
China

Phone	+86 (0)10 69311082
Email	chenghongjie1971@163.com

Study information

Primary study design	Interventional
Study design	Randomized double-blind placebo-controlled clinical trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled clinical trial
Study objectives	Compared with placebo, Tongxie Yaofang may be effective and safe for diarrhea-predominant irritable bowel syndrome.
Ethics approval(s)	Approved 04/02/2021, Medical Ethics Committee, Fangshan Hospital of Beijing University of Chinese Medicine (#151, Cheng-Guan-Nan Street, Fangshan District, Beijing, China; +86 (0)10-89321886; fsyyll@sina.com), ref: FZY LK-2021-002
Health condition(s) or problem(s) studied	Diarrhea-predominant irritable bowel syndrome
Intervention	Current intervention as of 05/07/2021: Participants are randomized into two groups using SAS software to generate a sequence of random numbers. One group receives Tongxie Yaofang, and the control group receives a placebo. The dosage given is 3.7 g of granules two times per day. The course of treatment is 8 weeks, and the patients will be followed up for 3 months after the treatment. _____ Previous intervention: Participants are randomized into two groups using SAS software to generate a sequence of random numbers. One group receives Tongxie Yaofang, and the control group receives a placebo. The dosage given is 18.75 g of granules two times per day. The course of treatment is 8 weeks, and the patients will be followed up for 3 months after the treatment.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Tongxie Yaofang
Primary outcome measure(s)	Current primary outcome measure as of 02/03/2022: 1. The degree of IBS symptom severity, measured using the scale of irritable bowel syndromes symptom severity score (IBS-SSS) at baseline, 4 weeks ± 3 days (duration of treatment), 8 weeks ± 3 days (end of treatment), 3 months ± 3 days (end of follow-up) Previous primary outcome measure: 1. The degree of IBS symptom severity, measured using the scale of irritable bowel syndromes symptom severity score (IBS-SSS) at baseline, 4 weeks ± 3 days (duration of treatment), 8 weeks ± 3 days (end of treatment), 3 months ± 3 days (end of follow-up) 2. Stool frequency: the average daily number of voluntary defecations recorded in the week before each timepoint at baseline, 4 weeks ± 3 days (duration of treatment), 8 weeks ± 3 days (end of treatment), 3 months ± 3 days (end of follow-up) 3. Stool consistency measured using the Bristol stool scale at baseline, 4 weeks ± 3 days (duration of treatment), 8 weeks ± 3 days (end of treatment), 3 months ± 3 days (end of follow-up)
Key secondary outcome measure(s)	Current secondary outcome measures as of 02/03/2022: 1. Stool frequency: the average daily number of voluntary defecations recorded in the week before each timepoint at baseline, 4 weeks ± 3 days (duration of treatment), 8 weeks ± 3 days (end of treatment), 3 months ± 3 days (end of follow-up) 2. Stool consistency measured using the Bristol stool scale at baseline, 4 weeks ± 3 days (duration of treatment), 8 weeks ± 3 days (end of treatment), 3 months ± 3 days (end of follow-up) 3. Quality of life measured using the scale of IBS-quality of life (IBS-QOL) at baseline, 8 weeks ± 3 days (end of treatment) 4. Anxiety measured using the self-rating anxiety scale (SAS) at baseline, 8 weeks ± 3 days (end of treatment) 5. Depression measured using the self-rating depression scale (SDS) at baseline, 8 weeks ± 3 days (end of treatment) 6. Safety assessed by: 4.1. Routine examination (blood routine, urine routine, stool routine + occult blood (OB)) at baseline, 8 weeks ± 3 days (end of treatment) 6.2. Biochemical indexes including liver function (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), kidney function (blood urea nitrogen (BUN), creatinine) measured at baseline, 8 weeks ± 3 days (end of treatment) 6.3. Heart electrical activity measured using electrocardiogram at baseline, 8 weeks ± 3 days (end of treatment) 6.4. Adverse events, such as rash, constipation, or other special symptoms, recorded at any time during the treatment by the patient: Incidence of adverse events = (number of adverse events / total cases) × 100% 6.5. Severe adverse events, such as loss of function or disability, life-threatening or even death, recorded at any time during the treatment by the researchers: incidence of severe adverse events = (number of severe adverse events / total cases) × 100% Previous secondary outcome measures: 1. Quality of life measured using the scale of IBS-quality of life (IBS-QOL) at baseline, 8 weeks ± 3 days (end of treatment) 2. Anxiety measured using the self-rating anxiety scale (SAS) at baseline, 8 weeks ± 3 days (end of treatment) 3. Depression measured using the self-rating depression scale (SDS) at baseline, 8 weeks ± 3 days (end of treatment) 4. Safety assessed by: 4.1. Routine examination (blood routine, urine routine, stool routine + occult blood (OB)) at baseline, 8 weeks ± 3 days (end of treatment) 4.2. Biochemical indexes including liver function (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), kidney function (blood urea nitrogen (BUN), creatinine) measured at baseline, 8 weeks ± 3 days (end of treatment) 4.3. Heart electrical activity measured using electrocardiogram at baseline, 8 weeks ± 3 days (end of treatment) 4.4. Adverse events, such as rash, constipation, or other special symptoms, recorded at any time during the treatment by the patient: Incidence of adverse events = (number of adverse events / total cases) × 100% 4.5. Severe adverse events, such as loss of function or disability, life-threatening or even death, recorded at any time during the treatment by the researchers: incidence of severe adverse events = (number of severe adverse events / total cases) × 100%
Completion date	31/12/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	65 Years
Sex	All
Target sample size at registration	96
Key inclusion criteria	Current inclusion criteria as of 05/07/2021: 1. Aged 18 to 65 years, male or female 2. Those who meet IBS-D Rome IV diagnostic criteria 3. Those who meet Liver Depression and Spleen Deficiency Syndrome (Ganyu Pixu Zheng) from the diagnostic criteria for TCM syndromes 4. IBS-SSS score ≥75 5. The patient did not take any drugs related to the treatment of the disease at least 1 week before entering the study and did not participate in other ongoing studies 6. Patients who have had a colonoscopy within 1 year and had an examination report 7. Accept the trial voluntarily and sign the informed consent form. The informed consent process complies with Good Clinical Practice (GCP) 8. Long-term residence in the place where the treatment is given _____ Previous inclusion criteria: 1. Aged 18 to 65 years, male or female 2. Those who meet IBS-D Rome IV diagnostic criteria 3. Those who meet Liver Depression and Spleen Deficiency Syndrome (Ganyu Pixu Zheng) from the diagnostic criteria for TCM syndromes 4. IBS-SSS score ≥75 5. The patient did not take any drugs related to the treatment of the disease at least one week before entering the study and did not participate in other ongoing studies 6. Patients who had a colonoscopy at a 3A (Tertiary) hospital within 1 year and had an examination report 7. Accept the trial voluntarily and sign the informed consent form. The informed consent process complies with Good Clinical Practice (GCP) 8. Long-term residence in the place where the treatment is given
Key exclusion criteria	Current exclusion criteria as of 05/07/2021: 1. Irritable bowel syndrome with predominant irregular bowel habits 2. Patients with severe tumors or organic lesions in the heart, liver, or kidney 3. Patients with severe mental illness or language disorders that affect communication 4. Patients with severe tumors or organic lesions in gastrointestinal tract, such as pancreatitis, history of colon or rectal cancer, intestinal tuberculosis, ulcerative colitis or Crohn's disease 5. Patients with metabolic diseases affecting gastrointestinal motility, such as hyperthyroidism 6. Those who with an allergic constitution or allergic to the composition of the studied medication 7. Patients with a history of gastrointestinal surgery 8. Pregnant or lactating women, and women planning to have a child or fertility treatment _____ Previous exclusion criteria: 1. Irritable bowel syndrome with predominant irregular bowel habits 2. Patients with tumors or organic lesions in the heart, liver, kidney, etc 3. Patients with mental illness 4. Patients with tumors or organic lesions in gastrointestinal tract, such as pancreatitis, intestinal polyps (excluding those with polypectomy for more than half a month), intestinal diverticulum, history of colon or rectal cancer, history of inflammatory bowel disease, intestinal tuberculosis, etc 5. Patients with metabolic diseases that affect the dynamics of the digestive tract, e.g., thyroid disease, diabetes, etc 6. Those who with allergic constitution or allergic to the composition of the studied drug 7. Patients with a history of abdominal or pelvic surgery, such as cholecystectomy 8. In light of the investigator's judgment, the patient has a situation that reduces the likelihood of enrollment or complicates enrollment, e.g., frequent changes in the work environment and other situations that are prone to loss of follow-up
Date of first enrolment	01/11/2021
Date of final enrolment	01/04/2022

Locations

Countries of recruitment

China

Study participating centre

Fangshan Hospital of Beijing University of Chinese Medicine

#151, Cheng-Guan-Nan Street
Fangshan District
Beijing
102400
China

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Shi-Bing Liang (zyi20126185@163.com).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		27/01/2025	28/01/2025	Yes	No
Protocol article		21/03/2022	08/04/2024	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

28/01/2025: Publication reference added.
08/04/2024: Publication reference added.
02/03/2022: The following changes have been made:
1. The primary outcome measure has been updated.
2. The secondary outcome measures have been updated.
05/07/2021: The following changes have been made:
1. The intervention has been changed.
2. The participant inclusion criteria have been changed.
3. The participant exclusion criteria have been changed.
4. The target enrolment number has been changed from 94 to 96.
5. The plain English summary has been updated to reflect the above changes.
23/03/2021: Trial's existence confirmed by the Medical Ethics Committee, Fangshan Hospital of Beijing University of Chinese Medicine.