Cheno Effect on Transit in Health and IBS-C
Condition: Constipation-predominant Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation
Study type: Interventional
Phase: Phase 2

Summary: 
      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).
    

Detailed description: 
      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).

      Scintigraphic gastric emptying and intestinal/colonic transit analysis: A variable region of
      interest program will be used to measure transit, as in previous studies from our lab.
      Radioisotope content in each region (gastric, ascending, transverse, descending,
      rectosigmoid) will be corrected for decay and tissue attenuation or depth.

      Anticipated Result: CDC will accelerate whole colonic transit and loosen stool form in
      patients with constipation predominant IBS.
    

Intervention name(s): Sodium chenodeoxycholate (NaCDC); Placebo
Intervention type(s): Drug; Other
Intervention description(s): 500 or 1000 milligrams NaCDC per day each for a period of 4 days; Placebo capsules with identical appearance to the study drug were prepared by the Mayo Clinic research pharmacy.
Other intervention name(s): Chenodiol
Intervention MeSH terms: Chenodeoxycholic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: chenodeoxycholate, IBS, transit, colon, constipation