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

Primary Purpose

Chronic Constipation, Methanogenesis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lubiprostone
Lubiprostone Control
Sponsored by
Augusta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Constipation, Methanogenesis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Iowa Hospitals and Clinics
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lubiprostone

Placebo

Arm Description

24mcg BID for 4 weeks, oral medication

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

Outcomes

Primary Outcome Measures

Change in Methane Production
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

Stool Frequency (Complete Spontaneous Bowel Movements)
change in mean stool frequency (delta) between baseline week and final week of study
Percentage Change in the Colonic Transit Time
Percentage change of colonic transit time between the baseline colonic transit study and the colonic transit study at the end of study
Peak Methane Value
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

Full Information

First Posted
August 25, 2010
Last Updated
July 20, 2018
Sponsor
Augusta University
Collaborators
Takeda Pharmaceuticals North America, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01190020
Brief Title
Effect of Lubiprostone on Methanogenesis and Bowel Function in Chronic Constipation.
Official Title
Effect of Lubiprostone on Methanogenesis and Bowel Function in Chronic Constipation
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Augusta University
Collaborators
Takeda Pharmaceuticals North America, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Constipation, Methanogenesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lubiprostone
Arm Type
Active Comparator
Arm Description
24mcg BID for 4 weeks, oral medication
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
24mcg BID for 4 weeks (placebo), oral medication
Intervention Type
Drug
Intervention Name(s)
Lubiprostone
Intervention Description
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
Intervention Name(s)
Lubiprostone Control
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Methane Production
Description
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.
Time Frame
Baseline and 1 month
Secondary Outcome Measure Information:
Title
Stool Frequency (Complete Spontaneous Bowel Movements)
Description
change in mean stool frequency (delta) between baseline week and final week of study
Time Frame
Baseline and 1 month
Title
Percentage Change in the Colonic Transit Time
Description
Percentage change of colonic transit time between the baseline colonic transit study and the colonic transit study at the end of study
Time Frame
Baseline and 1 month
Title
Peak Methane Value
Description
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
Time Frame
Baseline and 1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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). 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.
Facility Information:
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States

12. IPD Sharing Statement

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

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