Lubiprostone, Colonic Motility and Sensation

NCT00953043 | Completed Phase 4 Results DMC

• 4 other identifiers: 07-001438K24DK002638R01DK054681UL1RR024150
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

lubiprostone; colon; motility; sensation

Outcome Measures

Primary Outcomes (4)

• Colonic Compliance

  Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume of the colon. After the barostat catheter was inserted in the colon, the catheter was connected to a barostat machine. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg up to 64 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.

  1 hour after third dose of lubiprostone or placebo, on Day 3

• Fasting Colonic Tone

  Colonic tone is a measurement of the volume of the colon. Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon).

  30 minutes after the colonic tube placement, on Day 3

• Postprandial Colonic Tone

  Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon).

  30 minutes after standard meal, on Day 3

• Pain Sensation Ratings in Response to Colonic Distension at 32 mm HG Above Baseline Operating Pressure

  Pain was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain.

  approximately 1 hour after colonic tube placement, on Day 3

Secondary Outcomes (4)

• Gas Sensation Ratings in Response to Colonic Distensions at 32 mm Hg Above Baseline Operating Pressure

  approximately 1 hour after colonic tube placement, on Day 3

• Median Pressure When First Sensation Was Reported by 50% of Participants

  approximately 45 min after colonic tube placement, on Day 3

• Median Pressure When Gas Sensation Was First Reported by 50% of Participants

  approximately 45 min after colonic tube placement, on Day 3

• Median Pressure When Pain Sensation Was First Reported by 50% of Participants

  approximately 45 min after colonic tube placement, on Day 3

Study Arms (2)

Lubiprostone

ACTIVE COMPARATOR

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

Drug: lubiprostone; Other: Bowel preparation

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Other: Bowel preparation

Interventions

lubiprostone DRUG

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

Also known as: Amitiza

Lubiprostone

Placebo DRUG

Placebo medication given for three days

Placebo

Bowel preparation OTHER

Polyethylene glycol-based bowel preparation

Also known as: NuLytely

Lubiprostone; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator
• Takeda: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 19033530 BACKGROUND

MeSH Terms

Interventions

Lubiprostone; Cathartics; polyethylene glycol 3350

Intervention Hierarchy (Ancestors)

Alprostadil; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Gastrointestinal Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

This study was conducted in healthy subjects and needs replication in patients with Irritable Bowel Syndrome.

Results Point of Contact

• Title: Dr. Michael Camilleri, Professor of Medicine and Physiology, Gastroenterology
• Organization: Mayo Clinic

[email protected]

507-266-2305

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: September 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2009
• Last Updated: February 27, 2012
• Results First Posted: February 9, 2012

Record last verified: 2012-02

Locations

US (1)