Midazolam(drug), digoxin (drug) and Bupropion (drug) and Methadone (drug) in Substance-Related Disorders - Clinical Trials Registry

Study Overview

Status

Unknown

Conditions

Substance-Related Disorders

Intervention / Treatment

Detailed Description

Methadone maintenance treatment (MMT) has been used to rehabilitate the opiate addict resulting in a higher quality of life for the patient as well as improving social and psychological functioning while reducing the overall cost to society. The maintenance dose of methadone is highly variable between patients, and drug-drug interactions have been observed between methadone and various medications used to treat a variety of diseases. Identification and understanding of the enzymes responsible for the metabolism of methadone could potentially lead to improved strategy in individualizing methadone dosing and reduce the risk of adverse drug interactions.

Several cytochrome P450 enzymes (CYPs) have been identified and hypothesized to be involved in methadone metabolism in vitro, particularly CYP2B6 and CYP3A4. However, the quantitative contribution of CYP2B6 and CYP3A4 in the elimination clearance of methadone in vivo remains undefined. In addition, methadone is a substrate of the efflux transporter, P-glycoprotein (Pgp) at the intestinal mucosa. We are proposing a pilot study in healthy human subjects to investigate the following hypotheses:

Pgp limits the gastrointestinal absorption
Inter-subject variations in CYP2B6 and CYP3A4 activities explain the variation in methadone clearance in vivo

This will be accomplished by correlating the pharmacokinetics of methadone and the phenotype probes for Pgp (digoxin), CYP2B6 (bupropion) and CYP3A4 (midazolam). We plan to use these data to design a human subject study to assess the utility of MDR1 and CYP genotyping in predicting the methadone maintenance dose in a cohort of MMT patients.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Washington
  - Seattle, Washington, United States, 98105
    - Recruiting
    - University of Washington General Clinical Research Center
    - Principal Investigator:
      
      Rheem A Totah, PhD
    - Principal Investigator:
      
      Danny Shen, PhD
    - Sub-Investigator:
      
      Gregory Terman, MD
    - Sub-Investigator:
      
      Kristin K Patton, MD
    - Sub-Investigator:
      
      Jean C Dinh, BS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Healthy
Within 25% of ideal body weight

Exclusion Criteria:

Pregnant
A prisoner
Enemy, non-combatant
Smoker
Have a history of liver disease
Have a history of heart disease
Have a history of drug abuse
Currently on prescription medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: BASIC_SCIENCE
Allocation: NA
Interventional Model: SINGLE_GROUP
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Explore if there is a correlation between the areas of the concentration curves of probe substrates for CYP3A4 and/or CYP2B6 and Pgp and the area of the concentration curve of methadone. Time Frame: two years	two years

Secondary Outcome Measures

Outcome Measure	Time Frame
LC-MS assays will be developed to analyze the plasma content of the probe substrates, methadone and their metabolites. Specifically, midazolam, 1-OH midazolam, bupropion, t-butyl-hydroxy bupropion, digoxin, methadone, and EDDP (a methadone metabolite). Time Frame: two years	two years
Isolate and bank the DNA of the subjects for future genotyping of variant alleles that will be identified in this study to be important in methadone pharmacokinetics. Time Frame: two years	two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Investigators

Principal Investigator: Rheem A Totah, PhD, University of Washington, Medicinal Chemistry Department

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (ANTICIPATED)

January 1, 2011

Study Completion (ANTICIPATED)

January 1, 2011

Study Registration Dates

First Submitted

July 18, 2007

First Submitted That Met QC Criteria