Effects of Lubiprostone on Gastrointestinal Transit & pH in Irritable Bowel Syndrome (IBS) With Constipation

NCT01162863 | Completed Results

• 1 other identifier: 08-028LUB
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Irritable Bowel Syndrome; Constipation

Keywords

IBSC; irritable bowel syndrome; constipation

Outcome Measures

Primary Outcomes (1)

• Change in Gastric Emptying Time, Small Bowel Transit Time, Colon Transit Time and Whole Gut Transit Time From Baseline

  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 Outcomes (2)

• Change in Small Bowel pH and Colon pH From Baseline

  21-28 days

• Change in Motility Pattern of the Small Bowel and Colon From Baseline as Defined by the Motility Index

  21-28 days

Study Arms (3)

Lubiprostone 8 mcg BID

ACTIVE COMPARATOR

Drug: Lubiprostone; Other: Smartpill wireless motility capsule

Lubiprostone 24 mcg QD

ACTIVE COMPARATOR

Drug: Lubiprostone; Other: Smartpill wireless motility capsule

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Other: Smartpill wireless motility capsule

Interventions

Lubiprostone DRUG

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

Lubiprostone 24 mcg QD; Lubiprostone 8 mcg BID

Placebo DRUG

taken orally for 28 days

Placebo

Smartpill wireless motility capsule OTHER

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

Lubiprostone 24 mcg QD; Lubiprostone 8 mcg BID; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• \. 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

Sponsors & Collaborators

• University of Michigan: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (1)

University of Michigan Health System

Ann Arbor, Michigan, 48103, United States

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome; Constipation

Interventions

Lubiprostone

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alprostadil; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Limitations and Caveats

This was a small study with wide variability among participants, so data should be interpreted with great caution.

Results Point of Contact

• Title: Dr. Richard J Saad
• Organization: University of Michigan

rsaad@umich.edu

734-936-4780

Study Officials

• Richard Saad

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 15, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 27, 2017
• Results First Posted: January 27, 2017

Record last verified: 2016-12

Locations

US (1)