Clinical trial NCT00953043: Lubiprostone, Colonic Motility and Sensation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy
Keywords: lubiprostone
colon
motility
sensation
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
name: Takeda
First posted: 2009-08-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Colonic Compliance
timeFrame: 1 hour after third dose of lubiprostone or placebo, on Day 3
measure: Fasting Colonic Tone
timeFrame: 30 minutes after the colonic tube placement, on Day 3
measure: Postprandial Colonic Tone
timeFrame: 30 minutes after standard meal, on Day 3
measure: Pain Sensation Ratings in Response to Colonic Distension at 32 mm HG Above Baseline Operating Pressure
timeFrame: approximately 1 hour after colonic tube placement, on Day 3
Secondary outcomes:
measure: Gas Sensation Ratings in Response to Colonic Distensions at 32 mm Hg Above Baseline Operating Pressure
timeFrame: approximately 1 hour after colonic tube placement, on Day 3
measure: Median Pressure When First Sensation Was Reported by 50% of Participants
timeFrame: approximately 45 min after colonic tube placement, on Day 3
measure: Median Pressure When Gas Sensation Was First Reported by 50% of Participants
timeFrame: approximately 45 min after colonic tube placement, on Day 3
measure: Median Pressure When Pain Sensation Was First Reported by 50% of Participants
timeFrame: approximately 45 min after colonic tube placement, on Day 3
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.