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

NCT ID: NCT01190020

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2012-03-31

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.

Conditions

Chronic Constipation, Methanogenesis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Lubiprostone

24mcg BID for 4 weeks, oral medication

Group Type: ACTIVE_COMPARATOR

Lubiprostone

Intervention Type: DRUG

Colonic transit study performed and stool/symptom diaries will be reviewed. Eligible subjects will be given a lactulose breath test and randomized to Lubiprostone or placebo. Treatment group receives 24 mcg Lubiprostone twice daily and placebo group receives pills (identical in appearance to the study drug) for one month. Subjects will be asked to maintain a daily stool/symptom diary for duration of the study. In the middle of the study a research coordinator will call the subjects to take questions/concerns and record adverse events. Lactulose breath test will be repeated, constipation questionnaire filled out, colon transit study performed.

Placebo

24mcg BID for 4 weeks (placebo), oral medication

Group Type: PLACEBO_COMPARATOR

Lubiprostone Control

Intervention Type: DRUG

Colonic transit study performed and stool/symptom diaries will be reviewed. Eligible subjects will be given a lactulose breath test and randomized to Lubiprostone or placebo. Treatment group receives 24 mcg Lubiprostone twice daily and placebo group receives pills (identical in appearance to the study drug) for one month. Subjects will be asked to maintain a daily stool/symptom diary for duration of the study. In the middle of the study a research coordinator will call the subjects to take questions/concerns and record adverse events. Lactulose breath test will be repeated, constipation questionnaire filled out, colon transit study performed.

Interventions

Lubiprostone

Colonic transit study performed and stool/symptom diaries will be reviewed. Eligible subjects will be given a lactulose breath test and randomized to Lubiprostone or placebo. Treatment group receives 24 mcg Lubiprostone twice daily and placebo group receives pills (identical in appearance to the study drug) for one month. Subjects will be asked to maintain a daily stool/symptom diary for duration of the study. In the middle of the study a research coordinator will call the subjects to take questions/concerns and record adverse events. Lactulose breath test will be repeated, constipation questionnaire filled out, colon transit study performed.

Intervention Type: DRUG

Lubiprostone Control

Colonic transit study performed and stool/symptom diaries will be reviewed. Eligible subjects will be given a lactulose breath test and randomized to Lubiprostone or placebo. Treatment group receives 24 mcg Lubiprostone twice daily and placebo group receives pills (identical in appearance to the study drug) for one month. Subjects will be asked to maintain a daily stool/symptom diary for duration of the study. In the middle of the study a research coordinator will call the subjects to take questions/concerns and record adverse events. Lactulose breath test will be repeated, constipation questionnaire filled out, colon transit study performed.

Intervention Type: DRUG

Eligibility Criteria

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).

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role: collaborator

Augusta University

OTHER

Sponsor Role: lead

Responsible Party

Satish Rao

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

MS-LUB-106

Identifier Type: -

Identifier Source: org_study_id