Clinical trial NCT01162863: Effects of Lubiprostone on Gastrointestinal Transit & pH in Irritable Bowel Syndrome (IBS) With Constipation
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Constipation
Keywords: IBSC
irritable bowel syndrome
constipation
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals North America, Inc.
First posted: 2010-07-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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:

    1. Improvement with defecation
    2. Onset associated with a change in frequency
    3. 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)

  1. Loose (mushy) or watery stools for \>25% of bowel movements
  2. Hard or lumpy stools for \<25% of bowel movements
* Mixed IBS (IBS-M)

  1. Hard or lumpy stools \>25% of bowel movements
  2. 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

  1. 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
  2. Prokinetic agents:

     Metoclopramide, domperidone, erythromycin
  3. Anti-diarrheal agents:

     Loperamide, Diphenoxylate, Bismuth
  4. Anti-spasmotics:

     Dicyclomine, Hyoscyamine
  5. Opioid, narcotic, opioid/narcotic-containing analgesics:

     Morphine, Hydrocodone, Codeine, Methadone, Propoxyphene
  6. Probiotics
  7. Systemic antibiotics within last 3 months
  8. Recently initiated antidepressants (stable dose for \>2 months for non-GI conditions will be allowed)
  9. 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

  1. Previous surgery involving the stomach, small bowel or colon (prior appendectomy, cholecystectomy, polypectomy allowed)
  2. Previous history of small bowel obstruction for any reason
  3. History of any gastrointestinal malignancy
  4. History of dyssynergic defecation
  5. Unexplained nausea and vomiting
  6. History of inflammatory bowel disease (Crohn's or ulcerative colitis)
  7. History of microscopic colitis (lymphocytic or collagenous colitis)
  8. History of Hirschsprung's disease
  9. Severe or complicated diverticular disease
  10. Chronic pancreatitis
  11. History of celiac disease
  12. History of eating disorders (anorexia nervosa or bulimia)
  13. Cirrhosis
  14. Chronic hepatitis B or C infection
  15. HIV infection
  16. Diabetes
  17. Systemic sclerosis (scleroderma)
  18. Amyloidosis
  19. Untreated thyroid disease
  20. Chronic pulmonary disease
  21. Severe renal insufficiency or renal failure
  22. 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

Primary outcomes:
measure: Change in Gastric Emptying Time, Small Bowel Transit Time, Colon Transit Time and Whole Gut Transit Time From Baseline
timeFrame: 21-28 days
Secondary outcomes:
measure: Change in Small Bowel pH and Colon pH From Baseline
timeFrame: 21-28 days
measure: Change in Motility Pattern of the Small Bowel and Colon From Baseline as Defined by the Motility Index
timeFrame: 21-28 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: University of Michigan
name: Richard Saad
role: PRINCIPAL_INVESTIGATOR
References: