IBS, Diarrhea Predominant
Conditions
Brief summary
This trial is a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase III clinical trial. Its purpose is to evaluate the efficacy and safety of Changji'an Capsules in subjects with diarrhea-predominant irritable bowel syndrome (liver-qi invading spleen syndrome) after 8 weeks of treatment.
Interventions
DRUGChang Ji'an capsule
The prescription consists of 13 medicinal ingredients including Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae (processed), and Radix Astragali.
DRUGChang Ji'an capsule mimic
Mock capsules with "no pharmaceutically active ingredients", identical to the Chang Ji'an capsule in color, odor and appearance.
Sponsors
Beijing Hospital of Traditional Chinese Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Meet the Western medicine diagnostic criteria for diarrhea-predominant irritable bowel syndrome; 2. Meet the Traditional Chinese Medicine syndrome differentiation criteria for liver Qi invading the spleen; 3. Aged ≥18 and ≤65 years, regardless of gender; 4. Record daily the most severe abdominal pain, bloating, and abdominal discomfort NRS scores for the last week of the run-in period. At least one of these three items must meet the weekly average NRS score criterion (the weekly average of abdominal pain NRS is calculated as: total weekly score of abdominal pain NRS on days with Bristol Stool Form Scale type 6 or 7 stools / actual number of days with Bristol type 6 or 7 stools in that week; the average values for the other two items are calculated similarly) ≥3 points (11-point Numerical Rating Scale, NRS-11); meanwhile, for stool form, during the last week of the run-in period, there must be at least 2 days in which each day has at least one bowel movement of Bristol type 6 or 7; 5. Self-Rating Anxiety Scale (SAS) \<60 points and Self-Rating Depression Scale (SDS) \<63 points; 6. Have a colonoscopy result showing no obvious abnormalities (including diverticula or chronic inflammation) or colon polyps, based on colonoscopy results within 12 months prior at a tertiary hospital: 1.Colonoscopy results are normal with no organic changes; 2. Colonoscopy report shows minor abnormalities such as hemorrhoids or colonic polyps (diameter ≤5mm and number ≤3), which the investigator deems eligible for inclusion; 3. Previous colonoscopy reported colonic polyps with diameter \>5mm or number \>3, but after endoscopic treatment within 6 months prior to screening, remaining polyps are ≤5mm in diameter and ≤3 in number, deemed eligible by the investigator; 7. Agree to participate in this clinical trial and voluntarily sign the informed consent form.
Exclusion criteria
1. Individuals with fewer than 3 spontaneous bowel movements per week during the induction period; 2. Individuals with stool consistency of type 1 or 2 (Bristol Stool Form Scale) on at least 2 days per week during the induction period; 3. Individuals confirmed to have infectious diarrhea, inflammatory bowel disease, parasitic infection, positive fecal occult blood tests and considered to have gastrointestinal bleeding (excluding hemorrhoids), colorectal tumors, malabsorption syndrome, lactose intolerance (based on medical history), and diarrhea caused by systemic diseases; 4. Individuals who have used other medications for irritable bowel syndrome within 1 week prior to screening; 5. Individuals with non-IBS-D or other organic gastrointestinal lesions (excluding superficial gastritis, grade I erosive gastritis, or chronic atrophic gastritis found on endoscopy but deemed by the investigator to be eligible for inclusion (e.g., no mucosal erosion or bleeding observed endoscopically, and the patient has no upper abdominal fullness, upper abdominal pain, or acid reflux)), or other organic lesions that the investigator judges may cause abdominal pain, bloating, or discomfort; 6. Individuals with diabetes, hyperthyroidism, or serious primary diseases of the cardiovascular, cerebrovascular, liver, kidney, hematopoietic systems, or other serious diseases affecting survival (e.g., tumors), abnormal liver and kidney function (AST, ALT \> 1.5 times the upper limit of normal reference range, Scr above the upper limit of normal reference range), and clinically significant ECG abnormalities; 7. Individuals with other mental disorders (excluding mild anxiety or depression); 8. Individuals with a history of gastrointestinal surgery (excluding appendectomy or intestinal polyp removal); 9. Individuals who, within 2 weeks prior to screening, are using or need to continue using medications that may affect gastrointestinal function (anticholinergic drugs, 5-HT3 receptor antagonists, antidiarrheal drugs, antacids, prokinetic drugs, antidepressants (fluoxetine for at least 28 days), anti-anxiety drugs, intestinal microbiota regulators, traditional Chinese medicine decoctions, etc.); 10. Individuals allergic to 3 or more medications or foods, or known allergies to Xiangjie Capsules and its components, as well as emergency medication Pivabromium tablets; 11. Individuals who took emergency medication (Pivabromium tablets) during the last week of the induction period; 12. Individuals who took prohibited medications during the induction period; 13. Individuals suspected of or confirmed with a history of alcohol or drug abuse; 14. Pregnant women, breastfeeding women, or women of childbearing age planning to conceive; or female participants of childbearing potential and male participants (whose partners are women of childbearing potential) who do not agree to voluntarily use effective contraception from screening to 3 months after the last dose; 15. Individuals with cognitive impairment unable to provide fully informed consent; 16. Individuals positive for hepatitis B surface antigen, HIV antibody, hepatitis C antibody, or syphilis treponemal antibody; 17. Individuals who have participated in another clinical trial within the past month; 18. Individuals known to have familial colorectal cancer syndrome; 19. Individuals who, in the opinion of the investigator, have other factors making them unsuitable for inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate of diarrhea (stool characteristics) at the end of 8 weeks of treatment | Evaluation will be performed at Day 56. | Proportion of subjects who met the following criteria for at least 50% of the period from randomization to the end of Week 8 of treatment: patients with a reduction of at least 50% from baseline in the number of days per week with at least one stool that has a consistency of Type 6 or 7 Bristol Stool Score compared with baseline, and abdominal pain, abdominal distension and abdominal discomfort are unchanged or improved in comparison with baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The abdominal pain response rate at the end of treatment weeks 2, 4, 6 and 8 | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Proportion of subjects who satisfy the following criteria in no less than 50% of the treatment period from randomization to week endpoint: patients who experience a decrease in the weekly average of worst abdominal pain in the past 24 hours score of at least 30 percent compared with baseline, and the number of days per week with at least one stool with consistency of Type 6 or 7 that is the same as baseline or decreased and the number of stools of Type 6 or 7 on those days remains unchanged or decreased. |
| The response rate of diarrhea (stool form) at the end of treatment weeks 2, 4 and 6 | Evaluation will be performed at baseline and Day 14, Day 28, Day 42. | Proportion of subjects who met the following criteria for at least 50% of the period from randomization to week endpoint: patients with a reduction of at least 50% from baseline in the number of days per week with at least one stool that has a consistency of Type 6 or 7 Bristol Stool Score compared with baseline, and abdominal pain, abdominal distension and abdominal discomfort are unchanged or improved in comparison with baseline. |
| Treatment response rate at the end of treatment weeks 2, 4, 6 and 8 | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Defined as the proportion of subjects who meet the following criteria during at least 50% of the treatment period from randomization to the week endpoint: 1.Intensity of abdominal pain, abdominal distension and abdominal discomfort: a decrease in the weekly average of worst abdominal pain, abdominal distension and abdominal discomfort in the past 24 hours score of at least 30 percent compared with baseline; 2.Stool form: 50 percent or greater reduction in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. |
| Distention response rate at the end of treatment weeks 2, 4, 6 and 8 | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Proportion of subjects who satisfy the following criteria in no less than 50% of the treatment period from randomization to week endpoint: patients who experience a decrease in the weekly average of worst abdominal distention in the past 24 hours score of at least 30 percent compared with baseline, and the number of days per week with at least one stool with consistency of Type 6 or 7 that is the same as baseline or decreased and the number of stools of Type 6 or 7 on those days remains unchanged or decreased. |
| Response rate of abdominal discomfort at the end of 2, 4, 6, and 8 weeks of treatment | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Proportion of subjects who satisfy the following criteria in no less than 50% of the treatment period from randomization to week endpoint: patients who experience a decrease in the weekly average of worst abdominal discomfort in the past 24 hours score of at least 30 percent compared with baseline, and the number of days per week with at least one stool with consistency of Type 6 or 7 that is the same as baseline or decreased and the number of stools of Type 6 or 7 on those days remains unchanged or decreased. |
| Changes in the number of days with diarrhea in the past week compared to baseline at the end of 2, 4, 6, and 8 weeks of treatment | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Among patients with unchanged or improved intensity of abdominal pain, abdominal distension and abdominal discomfort, the change from baseline in the number of days with Bristol Stool Form Scale type 6 or 7 at least once during the week. |
| Changes in the average number of diarrhea episodes in the past week compared to baseline at the end of 2, 4, 6, and 8 weeks of treatment | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Defined as the change from baseline in the weekly frequency of Bristol Stool Form Scale Type 6 or 7 stools divided by 7 days, among patients whose intensity of abdominal pain, abdominal distension, and abdominal discomfort remained unchanged or improved. |
| Changes in Urgency Numeric Rating Scale(Likert 5 point scale, score range:0-4, Lower-is-Better endpoint) compared to baseline at the end of weeks 2, 4, 6, and 8, and in the past 2 weeks | Evaluation will be performed at baseline and D14, D28, D42, D56. | Assessed based on the change in defecation urgency score. |
| Changes from baseline in IBS Symptom Severity Score (IBS-SSS, score range:0-500, Lower-is-Better endpoint) at the end of 2, 4, 6, and 8 weeks of treatment. | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Assessed by the changes in scores of the IBS-SSS scales. |
| Changes from baseline in Quality of Life scale score (IBS-QOL, score range:0-136, Lower-is-Better endpoint) at the end of 2, 4, 6, and 8 weeks of treatment. | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Assessed by the changes in scores of the IBS-QOL scales. |
| Changes from baseline in Traditional Chinese Medicine syndrome score at the end of treatment weeks 2, 4, 6 and 8. | Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56. | Assessed by the changes in Traditional Chinese Medicine (TCM) syndrome scores. |
| Proportion of subjects with sustained remission and no worsening of diarrhea severity at Week 4 and Week 8 during the follow-up period. | Evaluations will be performed at baseline, 4 and 8 weeks of the follow-up period after the end of treatment. | Assessed via the Likert scale(Likert 7 point scale, score range:1-7, Lower-is-Better endpoint) completed in ePRO. |
| Proportion of subjects without diarrhea associated with diarrhea-predominant irritable bowel syndrome at follow-up Week 4 and Week 8. | Evaluations will be performed at Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56 after treatment completion. | Assessed via the Likert scale(Likert 7 point scale, score range:1-7, Lower-is-Better endpoint) completed in ePRO. |
| Usage of rescue medication | Evaluations shall be conducted at Week 8 of treatment. | Statistical analysis will be performed based on the consumption of rescue medication throughout the entire trial period. |
Countries
China
Contacts
CONTACTLuQing Zhao, Doctor
Outcome results
None listed