Lubiprostone, Colonic Motility and Sensation

NCT ID: NCT00953043

Last Updated: 2012-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2009-07-31

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lubiprostone

Subjects randomized to this arm received 24 micrograms of lubiprostone per day for three days.

Group Type: ACTIVE_COMPARATOR

lubiprostone

Intervention Type: DRUG

Lubiprostone 24 micrograms, one dose daily for three days in 30 subjects

Bowel preparation

Intervention Type: OTHER

Polyethylene glycol-based bowel preparation

Placebo

Subjects randomized to this arm received placebo medication for three days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo medication given for three days

Bowel preparation

Intervention Type: OTHER

Polyethylene glycol-based bowel preparation

Interventions

lubiprostone

Lubiprostone 24 micrograms, one dose daily for three days in 30 subjects

Intervention Type: DRUG

Placebo

Placebo medication given for three days

Intervention Type: DRUG

Bowel preparation

Polyethylene glycol-based bowel preparation

Intervention Type: OTHER

Other Intervention Names

Amitiza; NuLytely

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Takeda

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic

Principal Investigators

Michael Camilleri, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19033530 (View on PubMed)

Other Identifiers

K24DK002638

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01DK054681

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

07-001438

Identifier Type: -

Identifier Source: org_study_id