Effect of Lubiprostone on Methanogenesis and Bowel Function in Chronic Constipation.

Phase 1

Completed

Conditions: Chronic Constipation, Methanogenesis

Interventions: Drug: Lubiprostone Control
Drug: Lubiprostone

Registration Number: NCT01190020

Lead Sponsor: Augusta University

Brief Summary: Lubiprostone, a chloride channel activator, has been shown to improve symptoms of chronic constipation, largely by enhancing chloride-rich intestinal fluid secretion. Whether Lubiprostone has effects on colonic methanogenesis is not known. The investigators hypothesize that the effects of Lubiprostone may in part be due to its effects on altering colonic flora, particularly methanogenic flora.

By altering the colonic stasis of stool and through more efficient clearance of digestive residue, the investigators anticipate that Lubiprostone may either inhibit or promote better excretion of methanogenic flora, and thereby decrease the gut load of methane producing bacteria. In turn, this may lead to enhanced colonic smooth muscle contraction and an increased rate of spontaneous bowel movements and reduction of constipation symptoms.

The aim is to investigate the effects of Lubiprostone on intestinal methane production and bowel symptoms in patients with chronic constipation, by performing a randomized, double blind, placebo controlled study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

Inclusion Criteria

Constipation as defined by Rome III criteria13. Patients must have symptoms > 3 days/month for the past three months and report at least two of the following symptoms ≥ 25% of the time: straining, lumpy or hard stool, sensation of incomplete evacuation, sensation of anorectal obstruction/blockage, use of manual maneuvers, < 3 bowel movements/week. Also,they should have insufficient criteria for IBS, and only rarely loose stools without the use of laxatives.
≥ 3 ppm methane value at baseline1, 2(before sugar load).

Exclusion Criteria

Patients taking drugs that are known to be constipating will be excluded or asked to discontinue medications for at least 2 weeks and reassessed. For example, we will recommend that patients taking calcium channel antagonists contact their respective primary care physicians to explore alternative medications for hypertension such as beta blockers or ACE-inhibitors. If the calcium channel antagonists are able to be discontinued, patients will be re-screened at least two weeks after the medications are discontinued. If patients no longer meet inclusion criteria, they will be excluded from the study. Patients who remain constipated will be eligible for enrollment.
Patients with co-morbid illnesses such as severe cardiovascular disease, chronic renal failure, or those with previous gastrointestinal surgery except cholecystectomy and appendectomy
Patients with neurologic diseases such as multiple sclerosis, strokes, spinal cord injuries, and those who have problems with cognizance, i.e. a mini-mental score of <15 and/or are legally blind will be excluded.
Women who are pregnant or are likely to conceive during the course of the study will be excluded. Urinary pregnancy tests will be performed on all women of child-bearing potential prior to enrollment and before any x-ray of the abdomen.
Patients with Hirschsprung' s disease, or active local anorectal problems such as anal fissures, bleeding hemorrhoids, Crohn's, colitis, or colon cancer.
Patients with alternating constipation and diarrhea and those who fulfill the Rome-III criteria for irritable bowel syndrome.
Recent antibiotic use (last 6 weeks).
Patients using laxatives, PEG or Tegaserod and unwilling to discontinue these medications at least 2 weeks prior to the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Lubiprostone Control	24mcg BID for 4 weeks (placebo), oral medication
Lubiprostone	Lubiprostone	24mcg BID for 4 weeks, oral medication

Primary Outcome Measures

Name	Time	Method
Change in Methane Production	Baseline and 1 month	Change in the mean area under the curve of the breath hydrogen and methane gas profiles in parts per million, from time 0 to 120 minutes, between baseline versus mean area under the curve at the end of study.

Secondary Outcome Measures

Name	Time	Method
Stool Frequency (Complete Spontaneous Bowel Movements)	Baseline and 1 month	change in mean stool frequency (delta) between baseline week and final week of study
Peak Methane Value	Baseline and 1 month	The peak methane value measured during the baseline breath study will be compared with the peak methane obtained at the end of study breath test
Percentage Change in the Colonic Transit Time	Baseline and 1 month	Percentage change of colonic transit time between the baseline colonic transit study and the colonic transit study at the end of study

Trial Locations

Locations (2): University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States