Effect of Methylnaltrexone on GI Transit in Healthy Volunteers

Phase 4

Completed

• Conditions: Gastric Motility Disorder
• Interventions: Drug: Methylnaltrexone + codeine; Drug: Placebo + placebo; Drug: Methylnaltrexone only; Drug: Codeine only

• Registration Number: NCT01055704
• Lead Sponsor: Mayo Clinic

Brief Summary

This is a single-center, randomized, double blind, placebo-controlled study evaluating the effects of placebo, codeine, methylnaltrexone and codeine with methylnaltrexone on gastrointestinal motility and colonic transit of solids in healthy human subjects.

The hypotheses are:

1. Methylnaltrexone administered subcutaneously enhances gastrointestinal motility with acceleration of overall colonic transit, and ascending colon emptying of solids in healthy humans.

2. Methylnaltrexone significantly accelerates colonic transit that is delayed by codeine

Detailed Description

Methodology

Following the initial screening visit (visit 1), participants will be randomized to study medication, either 0.30mg/kg methylnaltrexone subcutaneously or placebo once daily and 30 mg codeine orally or placebo taken four times daily for a total of five days. Participants will be randomly assigned to study medication and allocation will be concealed. A urine pregnancy test will be performed for all females of child bearing potential within the 48 hours prior to the receipt of study medication. Note that females who are status post bilateral tubal ligation, hysterectomy or postmenopausal are exempted from this test. Study medication will be administered on study med days 1, 2 and 3 (visits 2, 3 and 4) at the Clinical Research Unit (CRU). Participants will return for scintigraphic assessment of gastric, small bowel and colonic transit of solids on study med days 4 and 5 (visits 5 and 6). The transit studies will be undertaken on over a 48 hour time period; no study medication is given on the final day of transit (visit 7).

Investigational product, dosage, mode of administration, duration of treatment

0.30 mg/kg methylnaltrexone or placebo subcutaneously once daily and 30 mg codeine or placebo orally four times daily for five consecutive days.

Treatment groups

1. placebo + placebo (8 participants)

2. placebo + codeine 120mg (8 participants)

3. methylnaltrexone 0.30 mg/kg + placebo (16 participants)

4. methylnaltrexone 0.30 mg/kg + codeine 120 mg (16 participants)

Efficacy assessments

1. Scintigraphic gastrointestinal and colonic transit

2. Assessment of bowel pattern frequency and consistency made by the patient using the bowel pattern diary

Safety assessments

No safety assessments (routine laboratory analysis, ECG etc) will be performed as both methylnaltrexone and codeine are FDA approved medications

Statistical analysis

The overall effects of the methylnaltrexone treatment on the primary and secondary response measures will be assessed using an analysis of covariance (ANCOVA) with suitable transformation for skewness in the distributions of measured responses if necessary (e.g., ANCOVA on ranks or an arcsine square root transformation for the proportion of marker in the colon at 6 hours). The covariates considered for inclusion in the analyses will be age, gender and body mass index. An a priori anticipated contrast (overall drug vs. placebo) will be examined (α = 0.05). The specific comparisons of methylnaltrexone vs placebo and codeine vs codeine plus methylnaltrexone are of significant interest, and since they are related to specific hypotheses, no change in α from 0.05 is planned.

Study Timeline

• Study Start: 2009-11
• Study First Submitted: 2010-01-22
• Study First Submitted QC: 2010-01-25
• Study First Posted: 2010-01-26
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Results First Submitted: 2011-07-08
• Results First Submitted QC: 2011-07-08
• Results First Posted: 2011-08-08
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-20
• Last Update Posted: 2012-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methylnaltrexone + codeine	Methylnaltrexone + codeine	-
Placebo	Placebo + placebo	-
Methylnaltrexone	Methylnaltrexone only	-
Codeine	Codeine only	-

Primary Outcome Measures

Name	Time	Method
Colonic Geometric Center at 24 Hours	24 hours	The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Secondary Outcome Measures

Name	Time	Method
Stool Frequency	daily	Stool frequency was self reported in a daily bowel pattern diary for 13 days.
T1/2 of Gastric Emptying of Solid	4 hours
Colonic Filling at 6 Hours	6 hours	Percent of solids reaching the colon at 6 hours
T1/2 of Ascending Colon Emptying	24 hours
Colonic Geometric Center at 4 Hours	4 hours	The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Colonic Geometric Center at 48 Hours	48 hours	The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Stool Consistency as Reported From the Bristol Stool Scale	Daily	Bristol Stool Scale a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation, with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.

Trial Locations

Locations (1)

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States