- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01162863
Effects of Lubiprostone on Gastrointestinal Transit & pH in Irritable Bowel Syndrome (IBS) With Constipation
A Pilot Study to Assess the Effects of Lubiprostone on Gastrointestinal and Colonic Motility and pH in Patients With the Irritable Bowel Syndrome and Constipation (IBS-C)
Irritable bowel syndrome (IBS) is a common disorder which presents with abdominal pain or discomfort in association with altered bowel habit. IBS is further subcategorized as three types according to the predominant bowel movement pattern: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed-IBS (IBS-M). The exact causes of IBS remain incompletely understood, but proposed mechanisms include abnormal motility, visceral hypersensitivity, abnormal brain-gut interactions, psychological distress, and altered GI tract motility.
Lubiprostone, a novel drug that works by activating the colonic Chloride channel type 2(ClC-2), has been approved for use in patients with chronic idiopathic constipation and recently approved for the treatment of IBS-C in women aged 18 and older. By activating the ClC-2 chloride channel in the colon, lubiprostone allows more fluid secretion into the intestinal lumen which leads to softer stool consistency. In phase III clinical trials, patients with IBS-C receiving lubiprostone have reported improvements in many symptoms such as abdominal pain and constipation. However, there is limited physiologic data to explain how exactly lubiprostone improves IBS-C symptoms.
The Smartpill is a novel non-digestible capsule that is capable of measuring intraluminal pH, pressure, and temperature in the gastrointestinal (GI) tract. Smartpill has been shown to accurately measure whole gut as well as regional (i.e. stomach, small bowel, colon) transit time.
The primary aim of this study is to determine the effects of lubiprostone on whole GI tract transit, colonic transit, motility, and intraluminal pH in patients with IBS-C through evaluation with the Smartpill. The investigators propose to study the effect of lubiprostone vs. placebo on these parameters, and secondarily to evaluate changes in these parameters with differing doses of lubiprostone.
The investigators hypothesize that lubiprostone will increase whole GI and colonic transit compared to placebo in patient with IBS. the investigators do not expect a change in intraluminal pH with lubiprostone compared to placebo.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
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Michigan
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Ann Arbor, Michigan, United States, 48103
- University of Michigan Health System
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Males or females >18 years of age
Meet Rome III criteria for IBS[2]:
Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following:
- Improvement with defecation
- Onset associated with a change in frequency
- Onset associated with a change in form (appearance) of stool
- *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
Fulfill the Rome III stool consistency criteria for IBS-C[2]
- Hard or lumpy stools for >25% of bowel movements
- Loose (mushy) or watery stools for <25% of bowel movements
- Capable of independently completing all requirements of the study including returning for required visits
- Able to provide written informed consent for study participation
- Willing to discontinue prohibited medications during study participation
- Documentation of a normal colonoscopy within last 5 years if over age 50 years (or sigmoidoscopy if less than age 50)
- Documentation of normal thyroid stimulating hormone(TSH) level, complet blood count (CBC) and electrolyte panel within prior 3 years
- Females of childbearing potential must have a negative urine or serum pregnancy test at screening
Females of childbearing potential must use an effective means of contraception during the course of the study
- Hormonal (oral, injectable, implantable, cervical/vaginal rings or patches)
- Double-barrier (condoms and/or diaphragm with spermicides) or intrauterine devices provided under the care of a health care professional
- Abstinence, in this case documentation of counseling will be recorded
Exclusion Criteria:
- Unable to understand or provide written informed consent
- Pregnant or nursing
- Patients with IBS-D, IBS-M or unsubtyped IBS by Rome III criteria[2]
IBS with diarrhea (IBS-D)
- Loose (mushy) or watery stools for >25% of bowel movements
- Hard or lumpy stools for <25% of bowel movements
Mixed IBS (IBS-M)
- Hard or lumpy stools >25% of bowel movements
- Loose (mushy) or watery stools for >25% of bowel movements
Unsubtyped IBS
1. Insufficient abnormality of stool pattern to meet criteria for IBS-C, IBS-D or IBS-M
- Documented allergy or intolerance to lubiprostone
Failure of balloon expulsion test
- Inability to expel 50cc balloon within 1 minute
Use of drugs known to affect gastrointestinal motility
Laxatives (stable doses of fiber taken for minimum of 4 weeks will be allowed)
Osmotic laxatives:
Magnesium hydroxide, Polyethylene glycol,Lactulose, Sorbitol
Stimulant laxatives:
Bisacodyl, Anthraquinones (senna), Misoprostol
Prokinetic agents:
Metoclopramide, domperidone, erythromycin
Anti-diarrheal agents:
Loperamide, Diphenoxylate, Bismuth
Anti-spasmotics:
Dicyclomine, Hyoscyamine
Opioid, narcotic, opioid/narcotic-containing analgesics:
Morphine, Hydrocodone, Codeine, Methadone, Propoxyphene
- Probiotics
- Systemic antibiotics within last 3 months
- Recently initiated antidepressants (stable dose for >2 months for non-GI conditions will be allowed)
- Benzodiazepines * Subjects taking prohibited medications will be required to stop these at the screening visit and remain off of them until completion of the study.
- Initiation of dietary changes potentially altering bowel transit within 4 weeks
Comorbid medical problems that may affect gastrointestinal transit or motility
- Previous surgery involving the stomach, small bowel or colon (prior appendectomy, cholecystectomy, polypectomy allowed)
- Previous history of small bowel obstruction for any reason
- History of any gastrointestinal malignancy
- History of dyssynergic defecation
- Unexplained nausea and vomiting
- History of inflammatory bowel disease (Crohn's or ulcerative colitis)
- History of microscopic colitis (lymphocytic or collagenous colitis)
- History of Hirschsprung's disease
- Severe or complicated diverticular disease
- Chronic pancreatitis
- History of celiac disease
- History of eating disorders (anorexia nervosa or bulimia)
- Cirrhosis
- Chronic hepatitis B or C infection
- HIV infection
- Diabetes
- Systemic sclerosis (scleroderma)
- Amyloidosis
- Untreated thyroid disease
- Chronic pulmonary disease
- Severe renal insufficiency or renal failure
Current or recent history (within last 6 months) of:
Diverticulitis, Duodenal or gastric ulcer, Acute pancreatitis, Ileus
- Contraindications to SmartPill® (in addition to above):
Cardiac pacemaker, defibrillator, or other implanted electromagnetic device, Known Zenker's diverticulum, Dysphagia
Study Plan
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
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Ingestion of a small non-digestible capsule that measures temperature, pH and pressure of the immediate surrounds as it passes through the GI tract eventually exiting the body through the anus
taken orally for 28 days
|
Active Comparator: Lubiprostone 8 mcg BID
|
lubiprostone taken either at a dose of 8 mcg orally twice daily (BID) for 28 days or 24 mcg orally once daily (QD) for 28 days
Ingestion of a small non-digestible capsule that measures temperature, pH and pressure of the immediate surrounds as it passes through the GI tract eventually exiting the body through the anus
|
Active Comparator: Lubiprostone 24 mcg QD
|
lubiprostone taken either at a dose of 8 mcg orally twice daily (BID) for 28 days or 24 mcg orally once daily (QD) for 28 days
Ingestion of a small non-digestible capsule that measures temperature, pH and pressure of the immediate surrounds as it passes through the GI tract eventually exiting the body through the anus
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Gastric Emptying Time, Small Bowel Transit Time, Colon Transit Time and Whole Gut Transit Time From Baseline
Time Frame: 21-28 days
|
Change in gastric emptying time, small bowel transit time, colon transit time and whole gut transit time measured in hours based on a measurement done at baseline and then again at 3 weeks into the intervention within each treatment arm
|
21-28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Small Bowel pH and Colon pH From Baseline
Time Frame: 21-28 days
|
Change in the mean pH of the small intestine and colon based on a measurement done at baseline and then again at 3 weeks into the intervention.
|
21-28 days
|
Change in Motility Pattern of the Small Bowel and Colon From Baseline as Defined by the Motility Index
Time Frame: 21-28 days
|
Change in the motility index defined as the natural log [(sum of pressure amplitudes times the number of contractions) + 1] for the small bowel and colon based on a measurement done at baseline and then again at 3 weeks into the intervention.
|
21-28 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Richard Saad, University of Michigan
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Disease
- Signs and Symptoms, Digestive
- Gastrointestinal Diseases
- Colonic Diseases, Functional
- Colonic Diseases
- Intestinal Diseases
- Syndrome
- Irritable Bowel Syndrome
- Constipation
- Molecular Mechanisms of Pharmacological Action
- Membrane Transport Modulators
- Chloride Channel Agonists
- Lubiprostone
Other Study ID Numbers
- 08-028LUB
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Istanbul Medipol University HospitalTepecik Training and Research Hospital; Bozyaka Training and Research Hospital and other collaboratorsRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedTurkey
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University of ViennaCompleted
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