Lubiprostone, Colonic Motility and Sensation
Information source: Mayo Clinic
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: lubiprostone (Drug); Placebo (Drug); Bowel preparation (Other)
Phase: Phase 4
Status: Completed
Sponsored by: Mayo Clinic Official(s) and/or principal investigator(s): Michael Camilleri, MD, Principal Investigator, Affiliation: Mayo Clinic
Summary
This study is being done to evaluate the effects of lubiprostone, a drug approved and used
for constipation, on pattern of contractions of the colon and the colon's sensitivity to
distension.
Clinical Details
Official title: The Effect of Lubiprostone, a Chloride Channel Activator, on Colonic Sensorimotor Functions in Healthy Subjects. A Phase IV, Placebo-Controlled, Parallel Group Study
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Colonic ComplianceFasting Colonic Tone Postprandial Colonic Tone Pain Sensation Ratings in Response to Colonic Distension at 32 mm HG Above Baseline Operating Pressure
Secondary outcome: Gas Sensation Ratings in Response to Colonic Distensions at 32 mm Hg Above Baseline Operating PressureMedian Pressure When First Sensation Was Reported by 50% of Participants Median Pressure When Gas Sensation Was First Reported by 50% of Participants Median Pressure When Pain Sensation Was First Reported by 50% of Participants
Detailed description:
This was a trial of healthy adults to compare the effects of oral lubiprostone, 24 microgram
per day and placebo for three days, on sensation and contractions of the colon using
validated methods.
On days 1 and 2, participants took the study medication with their breakfast and recorded
the time. On day 2 starting at 4: 00 pm, participants started a polyethylene glycol-based
bowel preparation to cleanse the colon. After overnight bowl preparation, participants
reported fasting to the study center at 7: 00 am on day 3. Colonic sensorimotor functions
were assessed by an endoscopically placed barostat-manometric assembly.
After 30 minutes of rest following tube placement, fasting colonic tone, colonic compliance
and colonic sensation were tested. The last dose of medication was ingested and 1 hour
later the same colonic functions, as well as colonic response to a standardized meal of a
1,000-kilocalorie chocolate milkshake were assessed. The participant was able to leave the
study center in the afternoon, after a meal had been ingested (if desired).
Details on colonic tube placement: A flexible sigmoidoscopy was performed to evaluate the
left side of the colon and to place a Teflon-coated guide wire beyond the splenic flexure.
The colon was deflated as the sigmoidoscope was removed and a barostat catheter (constructed
at Mayo Clinic, Rochester, MN) with six manometric point sensors and a polyethylene balloon
was introduced into the colon over the guide wire. The barostat catheter was positioned in
the mid-descending or upper sigmoid colon with the aid of fluoroscopy. The final position of
the barostatically controlled balloon was confirmed by fluoroscopy. After the colonic tube
placement, participants rested for 30 min. The catheter was connected to a rigid piston
barostat machine. After transient inflation of the barostat bag to a volume of 75 ml to
ensure it was unfolded, it was deflated. Thereafter, it was inflated in 2 mm Hg increments
to baseline operating pressure, which was defined as 2 mm Hg above the minimal distension
pressure at which respiratory excursions were clearly recorded by the barostat tracing.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion criteria:
- Healthy subjects
- Body mass index (BMI): 18 to 32.
- Negative pregnancy test for women of childbearing potential.
- Absence of gastrointestinal symptoms (abridged Bowel Disease Questionnaire).
- Signed informed consent.
Exclusion criteria:
- Subjects with body mass index (BMI) of less than 18 or more than 32.
- Structural or metabolic diseases/conditions that affect the gastrointestinal
(GI)system, or functional gastrointestinal disorders. For screening, the Bowel
Disease Questionnaire will be used to exclude subjects with irritable bowel syndrome.
- Use of drugs or agents within the past 2 weeks that alter GI transit including
laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin,
narcotics, anticholinergics, tricyclic antidepressants, SSRI and newer
antidepressants.
NOTE: Low stable doses of thyroid replacement, estrogen replacement, low dose aspirin for
cardioprotection, and birth control pills or depot injections are permissible.
- Use of drugs or agents within the 2 weeks prior to screening that may add drowsiness
and central nervous system (CNS) depression such as barbiturates, benzodiazepines,
ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS
depressants.
- Female subjects who are pregnant or breast feeding.
- Females must be either surgically sterilized, postmenopausal (>12 months since last
menses) or, if of childbearing potential, using reliable methods of contraception as
determined by the physician (single-barrier methods alone and rhythm methods are not
acceptable).
- Clinical evidence (including physical exam and ECG) of significant cardiovascular,
respiratory, renal, hepatic, gastrointestinal, hematological, neurological,
psychiatric, or other disease that interfere with the objectives of the study. Any
candidate participants with such disorder mentioned will be referred to their general
physician.
- The Hospital Anxiety and Depression Scale (HADS) will be used to exclude subjects
with significant affective disorders, as well as to determine anxiety and depression
scores at the start of the study. Any candidate participants with such disorder
mentioned will be referred to their general physician.
- Symptoms of a significant clinical illness in the two weeks prior to screening.
- Participation in another clinical study within the 30 days prior to screening.
- Subjects who are considered by the investigator to be alcoholics not in remission or
known substance abusers.
Locations and Contacts
Mayo Clinic, Rochester, Minnesota 55905, United States
Additional Information
Mayo Clinic Clinical Trials
Related publications: Sweetser S, Busciglio IA, Camilleri M, Bharucha AE, Szarka LA, Papathanasopoulos A, Burton DD, Eckert DJ, Zinsmeister AR. Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G295-301. doi: 10.1152/ajpgi.90558.2008. Epub 2008 Nov 25.
Starting date: September 2007
Last updated: February 23, 2012
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