Randomized Placebo Controlled Trial of Traditional Chinese Medicine for Treatment of Irritable Bowel Syndrome
试验速览
- 阶段
- 2 期
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Change from baseline in IBS-Symptom Severity Score at 8 weeks
研究概览
简要总结
Irritable bowel syndrome (IBS) is a prevalent condition that adversely affects patient's quality of life and represents a large health care burden globally. Currently, there is no satisfactory treatment for IBS and Chinese Herbal medicine (CHM) has been suggested to be potentially useful. However, the efficacy of CHM in the treatment of IBS is unclear and its mechanism of action is unknown. To date, attempts to characterize CHM efficacy universally suffer from poor scientific method or they do not faithfully replicate authentic CHM best practice. The overall goal of this proposal is hence to address these deficiencies by combining the best of CHM with western medicine.The investigators propose a 10-week randomized, double-blind, placebo-controlled study on 104 patients that form the intersect between western medicine and CHM. The participants would fulfill ROME III criteria for IBS-Constipation predominant subtype, which is also the TCM (Traditional Chinese Medicine) syndrome of Liver Qi stagnation. The investigators will test a core herbal formula specific for treatment of Liver Qi stagnation against placebo that consist of only 10% active ingredients but which is indistinguishable by taste from active treatment. Efficacy will be assessed by comparing symptoms reported at baseline (2-week run-in period) to end of treatment (8 weeks) and an optional follow up period (12 weeks). The primary end point will be improvement in IBS-Symptom Severity Score. Mechanism of action will be explored by measuring changes to the stool microbiome and GI transit times. If successful, this trial would provide one of the first evidence- and mechanism-based approach to translate CHM into mainstream IBS management.
详细描述
This will be a 10 week randomized, double blind, parallel group, single center study on patients who fulfil ROME III criteria for IBS-Constipation predominant subtype (IBS-C) and TCM syndrome of Liver Qi stagnation.The study will consist of a two week baseline run-in period without medication, an 8 week randomized double blind treatment period with either placebo or CHM (twice daily), followed by an optional further 12 week withdrawal period with no medication.
Patients who fulfill ROME III criteria for IBS-C will be assessed by a designated qualified traditional Chinese physician. Patients who fulfill TCM syndrome diagnosis of Liver Qi stagnation will be eligible participate in the study.
Each patient's TCM syndrome differentiation and modifications as well as corresponding prescription will be assessed by a second TCM physician to evaluate for reproducibility of TCM diagnosis.
The TCM physician will prescribe the appropriate treatment formula based on TCM principles (see intervention section):
Placebo will constitute granules with 10% active core ingredients. This choice of placebo has been validated in a thesis which showed that the decoction compounded this way was indistinguishable by an intelligent sensory machine in taste, smell and appearance compared to the active treatment formula while not possessing any significant therapeutic effect in animal models
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ethnic group: Chinese only
- •Presence of FGID as determined by managing physician and fulfil ROME III criteria for IBS-C
- •To be eligible for randomization, patients will need to report during the baseline period:
- •o IBS-symptom severity score (SSS) of ≥150
- •Physical examination without clinically relevant abnormalities
- •Completed a relevant colonic imaging (e.g. colonoscopy, barium enema, or other colonic imaging) within 60 months before enrolment that shows absence of structural abnormality which could account for the patient's symptom as determined by the managing physician
- •o Patients below the age of 45 without colonic imaging must have stable IBS-C symptoms for at least 5 years (without evidence of rectal bleeding, weight loss, recent changes in bowel habits, family history of colorectal cancer or anaemia)
- •Completed blood test
- •Haemoglobin within range of 11-17g/dL (for females), and 13-19g/dL (for males) Abnormal haemoglobin which is accounted for by a non-GI-related condition (e.g. thalassemia), as determined by managing physician, is allowed
- •Blood tests taken 3 months or longer before enrolment are considered invalid
- •Completed 12-Lead ECG
- •No clinically relevant abnormalities in 12-lead ECG performed for this study and in laboratory findings
- •12-Lead ECG taken 3 months or longer before enrolment are considered invalid
- •Oral contraceptives are allowed provided that they have not been changed in the previous 6 months before the start of the run-in period
- •The patient has the ability to provide informed consent
- •Patient is willing to be compliant with study procedures including, and will be contactable by phone for weekly IBS treatment and symptoms
- •Mentally competent, able to give written informed consent prior to any study-related procedure and compliant to undergo all visits and procedures scheduled in the study.
排除标准
- •BMI <16 or >35 A history of surgery to remove a segment of the gastrointestinal tract or bariatric surgery for obesity at any time; appendectomy/cholecystectomy within 2 months or other abdominal surgeries within 6 months before entry into the trial; history of diverticulitis or any chronic condition that could be associated with abdominal pain or discomfort and could confound the assessments in this trial; or a history of laxative abuse. Investigations for exclusion of structural abnormality will be performed as per regional guideline (19).
- •Failure to discontinue medication prior to study, specifically:
- •antibiotics and probiotic consumption within the last 1 month
- •CHM medications within the last 2 weeks
- •All medications except bisacodyl (rescue medication) which may alter GI motility will also have to be stopped during the 2 weeks run-in period.
- •o Patients are allowed to take rescue medication if in need, when abdominal pain or distension ≥70 on irritable bowel syndrome severity scoring system
- •Pregnancy or breastfeeding
- •Hypersensitivity to the drug excipients.
- •Patient is not able to understand or collaborate throughout the study.
- •Not currently or in the preceding 4 weeks enrolled in a clinical study with another investigational drug.
- •Patient has any condition that, in the opinion of the Investigator that would compromise the well-being of the patient or the requirements of the study.
- •Presence of ischaemic heart disease, diabetes mellitus, thyroid dysfunction or renal impairment (as determined by study investigators) or previous surgery or anatomical anomalies which may alter GI motility (as assessed by investigators)
- •Failure to maintain usual diet, lifestyle and exercise regimen throughout the study.
- •Patients with major psychiatric or neurological disorders
研究组 & 干预措施
10% active Placebo
Placebo will constitute granules with 10% active core ingredients as below:
White Peony Root 10g Processed Liquorice 3g Immature Bitter Orange 8g White Atractylodes Rhizome 15g
- 2 packets of sachets once before breakfast and once before dinner.
干预措施: TCM (Diagnostic Test)
Traditional Chinese Medication (TCM) Drug A,B,C,D
Traditional Chinese Medication (TCM) Drug A,B,C,D.
TCM Drug A:
White Peony Root 10g Processed Liquorice 3g Immature Bitter Orange 8g White Atractylodes Rhizome15g
TCM Drug B:
White Peony Root 10g Processed Liquorice 3g Immature Bitter Orange 8g White Atractylodes Rhizome 15g Liver stagnation with heaty transformation: add Scutellaria Root 5g、Prunella Spike 5g
TCM Drug C:
White Peony Root 10g Processed Liquorice 3g Immature Bitter Orange 8g White Atractylodes Rhizome 15g Prominent abdominal pain: White Peony Root to increase to 15g add Bupleurum Root 5g
TCM Drug D:
White Peony Root 10g Processed Liquorice 3g Immature Bitter Orange 8g White Atractylodes Rhizome 15g Hard stools: add Peach Kernel 5g、Areca Seed 5g
干预措施: TCM (Diagnostic Test)
结局指标
主要结局
Change from baseline in IBS-Symptom Severity Score at 8 weeks
时间窗: 8 weeks
Improvement in IBS-Symptom Severity Score
次要结局
未报告次要终点