Effect of Chenodeoxycholic Acid on Gastrointestinal Transit and Colonic Functions in Health and Constipation-predominant Irritable Bowel Syndrome (IBS-C)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Colonic Geometric Center at 24 Hours (GC24)
研究概览
简要总结
The study hypothesis is that the naturally occurring bile acid, chenodeoxycholic acid, induces acceleration of colonic transit in health and in patients with constipation-predominant Irritable Bowel Syndrome (IBS-C).
详细描述
Hypothesis: A hydrophobic di-alpha hydroxy bile salt, sodium chenodeoxycholate (CDC), delivered in a delayed release capsule to the ileocolonic region of the colon induces acceleration of colonic transit in patients with constipation-predominant IBS.
Methods: We shall study 36 patients with IBS-C, aged 18-65 years, and each treatment group will be balanced on gender and Body Mass Index (BMI) in the randomization. All patients will be assessed for symptoms of functional gastrointestinal disorder or psychological disturbance will be characterized in a standard fashion with questionnaires (Talley et al 1989), the Psychosomatic Symptom Checklist (SCL-90) and the Hospital Anxiety and Depression Inventory [HAD (Zigmond and Snaith 1983)]. With appropriate consent, a venous blood sample will be obtained from each participant for DNA extraction. Fasting Serum 7alpha-hydroxy-4-cholesten-3-one (7alpha-CHO) will be measured in all to ensure they do not have evidence of asymptomatic bile acid malabsorption. The normal range in our lab is <61 ng/mL.
Experimental design: A randomized, double blind, placebo controlled, dose-response parallel group design, with concealed allocation. Participants will undergo an initial baseline colonic transit for 24 hours to obtain Colonic Geometric Center (GC24). Sodium chenodeoxycholate (CDC) will be delivered to the ileocolonic region to assess ascending colon and whole colonic transit in participants with IBS-C; 12 participants per group will be randomized to placebo, 0.5 or 1 gram CDC each for a period of 4 days with the transit study conducted during the last 48 hours of drug ingestion. The CDC will be placed in gelatin capsules that are coated with methacrylate (EUDRAGIT-L®), a pH-sensitive polymer that will result in release of the active ingredient in the terminal ileum.
Experimental procedure: At standardized times (hourly for first 8 hours, and at 12, 24 and 48 h), dual gamma camera scans will be obtained to measure ascending colon and overall colonic transit. Patients will fill daily diaries to evaluate stool, frequency, consistency and ease of passage.
Gastrointestinal and Colonic Transit: A validated scintigraphic method to measure gastric, small bowel, and colonic transit will be used. A methacrylate-coated capsule dissolves in the alkaline pH of the distal ileum to release 111In-labeled activated charcoal particles to evaluate colonic transit on sequential scans. Meanwhile, orally ingested 99 mTc-labeled egg meal allows measurement of gastric and small bowel transit. (Technetium [99mTc] sestamibi (trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging.) We have previously shown that the gastric emptying (GE) at 2 and 4 hours, colonic filling (CF) at 6 hours, and colonic geometric center (GC, weighted average of isotopic counts) in colon at 4, 24 and 48 hours provide excellent summaries of gastric emptying and colonic transit with similar diagnostic accuracy as more detailed, costly, and time-consuming analyses. The normal values for these parameters have been previously published (Cremonini et al).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers:
- •Age (yr) 18-65
- •Gender (F:M)3.5 :1
- •Bowel Disease Questionnaire (BDQ) - IBS symptoms negative by Rome III criteria
- •Hospital Anxiety/Depression score <8
- •IBS patients:
- •Age (yr) 18-65
- •Gender (F:M) 5 :1
- •BDQ - IBS symptoms: positive by Rome III criteria
- •Hospital Anxiety/Depression score: No restrictions
排除标准
- •Abdominal surgery (except appendectomy or cholecystectomy)
- •GI medications during the 48h prior to transit measurement
- •Aspartate/Alanine transaminases >2 X Upper Limit of Normal (ULN)
- •Other Medications except stable doses of estrogen, thyroid, low dose antidepressants of the dopaminergic or serotonergic class
研究组 & 干预措施
NaCDC 500 mg
Participants randomized to this arm received 500 mg NaCDC per day for 4 days.
干预措施: Sodium chenodeoxycholate (NaCDC) (Drug)
NaCDC 1000 mg
Participants randomized to this arm received 1000 mg NaCDC per day for 4 days.
干预措施: Sodium chenodeoxycholate (NaCDC) (Drug)
Placebo
Participants randomized to this arm received a placebo capsule each day for 4 days.
干预措施: Placebo (Other)
结局指标
主要结局
Colonic Geometric Center at 24 Hours (GC24)
时间窗: after 4 days of treatment
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
次要结局
- Colonic Transit at 48 Hours (GC48)(after 4 days of treatment)
- Ascending Colon Emptying (AC t_1/2)(after 4 days' treatment)
- Stool Consistency(after 4 days' treatment)
- Colonic Filling at 6 Hours(after 4 days' treatment)