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

• Sponsor: Augusta University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01190020
• Collaborator: Takeda Pharmaceuticals North America, Inc. (Industry)
• Enrollment: 41
• Locations: 2
• Arms: 2
• Duration (Months): 36.9
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Constipation, Methanogenesis	Drug: Lubiprostone; Drug: Lubiprostone Control	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Lubiprostone on Methanogenesis and Bowel Function in Chronic Constipation
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lubiprostone 24mcg BID for 4 weeks, oral medication	Drug: 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.
Placebo Comparator: Placebo 24mcg BID for 4 weeks (placebo), oral medication	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.

Outcome Measures

Primary Outcome Measures

1. 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

1. Stool Frequency (Complete Spontaneous Bowel Movements) [Baseline and 1 month]

   change in mean stool frequency (delta) between baseline week and final week of study

2. 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

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
2	University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Augusta University
• Takeda Pharmaceuticals North America, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Satish Rao, PI, University of Iowa
• ClinicalTrials.gov Identifier: NCT01190020
• Other Study ID Numbers: MS-LUB-106
• First Posted: Aug 27, 2010
• Last Update Posted: Jan 15, 2019
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Constipation; Lubiprostone

Study Results

Participant Flow

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	Received 24 mcg of lubiprostone twice a day with meals.	Received placebo twice a day with meals.
Period Title: Overall Study
STARTED	29	12
COMPLETED	22	12
NOT COMPLETED	7	0

Baseline Characteristics

Arm/Group Title	Lubiprostone	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	29	12	41
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 89.7%	11 91.7%	37 90.2%
>=65 years	3 10.3%	1 8.3%	4 9.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.8 (11.9)	47.3 (22.5)	43.7 (13.7)
Sex: Female, Male (Count of Participants)
Female	25 86.2%	12 100%	37 90.2%
Male	4 13.8%	0 0%	4 9.8%
Region of Enrollment (participants) [Number]
United States	29 100%	12 100%	41 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

patients who completed the study were analyzed

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description
Measure Participants	22	12
Mean (Standard Error) [parts per million*minutes]	10645 (1481)	14635 (2330)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

subjects who completed the study

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description
Measure Participants	22	12
Mean (Standard Error) [bowel movements per week]	3.71 (0.84)	0.85 (0.54)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

subjects who completed the study

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description
Measure Participants	22	12
Mean (Standard Error) [percent]	0.23 (0.06)	0.48 (0.1)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description
Measure Participants	22	12
Mean (Standard Error) [parts per million]	51.3 (7.1)	70.5 (11.2)

Adverse Events

Arm/Group Title	Lubiprostone		Placebo
Arm/Group Description
All Cause Mortality
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/29 (13.8%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Chest Tightness	2/29 (6.9%)		0/12 (0%)
Shortness of Breath	2/29 (6.9%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.