Phase III Clinical Trial of Changji'an Capsules in the Treatment of Irritable Bowel Syndrome With Predominant Diarrhea (Liver-Qi Invading Spleen Syndrome)

Официальное название

Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial on the Efficacy and Safety of Changji'an Capsules in the Treatment of Irritable Bowel Syndrome With Predominant Diarrhea (Liver-Qi Invading Spleen Syndrome)

Обзор

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.

Вмешательства

• Препарат Chang Ji'an capsule
  The prescription consists of 13 medicinal ingredients including Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae (processed), and Radix Astragali.
• Препарат Chang Ji'an capsule mimic
  Mock capsules with "no pharmaceutically active ingredients", identical to the Chang Ji'an capsule in color, odor and appearance.

Первичные конечные точки

• Response rate of diarrhea (stool characteristics) at the end of 8 weeks of treatment [Срок оценки: Evaluation will be performed at Day 56.]

Вторичные конечные точки (12)

• The abdominal pain response rate at the end of treatment weeks 2, 4, 6 and 8 [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• The response rate of diarrhea (stool form) at the end of treatment weeks 2, 4 and 6 [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42.]
• Treatment response rate at the end of treatment weeks 2, 4, 6 and 8 [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• Distention response rate at the end of treatment weeks 2, 4, 6 and 8 [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• Response rate of abdominal discomfort at the end of 2, 4, 6, and 8 weeks of treatment [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• 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 [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• 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 [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• 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 [Срок оценки: Evaluation will be performed at baseline and D14, D28, D42, D56.]
• 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. [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• 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. [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• Changes from baseline in Traditional Chinese Medicine syndrome score at the end of treatment weeks 2, 4, 6 and 8. [Срок оценки: Evaluation will be performed at baseline and Day 14, Day 28, Day 42, Day 56.]
• Proportion of subjects with sustained remission and no worsening of diarrhea severity at Week 4 and Week 8 during the follow-up period. [Срок оценки: Evaluations will be performed at baseline, 4 and 8 weeks of the follow-up period after the end of treatment.]

Критерии участия

Критерии включения

• Meet the Western medicine diagnostic criteria for diarrhea-predominant irritable bowel syndrome;
• Meet the Traditional Chinese Medicine syndrome differentiation criteria for liver Qi invading the spleen;
• Aged ≥18 and ≤65 years, regardless of gender;
• 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;
• Self-Rating Anxiety Scale (SAS) <60 points and Self-Rating Depression Scale (SDS) <63 points;
• 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;
• Agree to participate in this clinical trial and voluntarily sign the informed consent form.

Критерии исключения

• Individuals with fewer than 3 spontaneous bowel movements per week during the induction period;
• Individuals with stool consistency of type 1 or 2 (Bristol Stool Form Scale) on at least 2 days per week during the induction period;
• 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;
• Individuals who have used other medications for irritable bowel syndrome within 1 week prior to screening;
• 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;
• 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;
• Individuals with other mental disorders (excluding mild anxiety or depression);
• Individuals with a history of gastrointestinal surgery (excluding appendectomy or intestinal polyp removal);
• 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.);
• 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;
• Individuals who took emergency medication (Pivabromium tablets) during the last week of the induction period;
• Individuals who took prohibited medications during the induction period;
• Individuals suspected of or confirmed with a history of alcohol or drug abuse;
• 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;
• Individuals with cognitive impairment unable to provide fully informed consent;
• Individuals positive for hepatitis B surface antigen, HIV antibody, hepatitis C antibody, or syphilis treponemal antibody;
• Individuals who have participated in another clinical trial within the past month;
• Individuals known to have familial colorectal cancer syndrome;
• Individuals who, in the opinion of the investigator, have other factors making them unsuitable for inclusion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 29 центров

• Beijing Hospital of Traditional Chinese Medicine — Пекин
• West China Hospital, Sichuan University — Чэнду
• Chongqing Traditional Chinese Medicine Hospital — Чунцин
• The First Affiliated Hospital of Guangzhou University of Chinese Medicine — Гуанчжоу
• The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine — Guizhou
• Haozhou People's Hospital — Haozhou
• Hebei Provincial Hospital of Traditional Chinese Medicine — Hebei
• The First Affiliated Hospital of Heilongjiang University of Chinese Medicine — Heilongjiang
• … и ещё 21 центр

Публикации

• Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med. 2016 Jan 21;374(3):242-53. doi: 10.1056/NEJMoa1505180. PMID 26789872
• Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9. PMID 23583433
• Wang Z, Xu M, Shi Z, Bao C, Liu H, Zhou C, Yan Y, Wang C, Li G, Zhang W, Gao A, Wu H. Mild moxibustion for Irritable Bowel Syndrome with Diarrhea (IBS-D): A randomized controlled trial. J Ethnopharmacol. 2022 May 10;289:115064. doi: 10.1016/j.jep.2022.115064. Epub 2022 Jan 31. PMID 35114338
• Corsetti M, Shin A, Lacy BE, Cash BD, Simren M, Schmulson MJ, Hou X, Lembo A. Bowel Disorders. Gastroenterology. 2026 May;170(6):1261-1282. doi: 10.1053/j.gastro.2026.02.003. Epub 2026 Feb 17. PMID 41713703
• Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22-32. doi: 10.1056/NEJMoa1004409. PMID 21208106

Идентификаторы

NCT: NCT07610434 · FA-CJA-III-2510

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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