Pilot Study of Entacapone for Methamphetamine Abuse

NCT02058966 | Completed Early Phase 1 Results DMC

• 3 other identifiers: 887410048053986
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Addiction to methamphetamine is a serious health problem. There are no medications that a doctor can give someone to help them stop using methamphetamine. Entacapone (Comtan©) is a medication that could help people addicted to methamphetamine. This study will see how entacapone works in healthy people who are given methamphetamine. We think that the study drug will be well tolerated, and that it will prevent some of the effects of methamphetamine that make it so addictive. We also want to see how differences in people's genes may cause differences in the ways the study drug and methamphetamine work for them. The study has six total visits. The first visit is for screening. Tests and procedures will make sure it is safe for subjects to participate. The second visit is a familiarization day. Subjects will receive methamphetamine, but no entacapone. This is done to make sure they can tolerate the drug and recognize its effects before being given a second drug on the same day. Subjects will take surveys and computer tests to see how the medications change mood, thinking, and liking the drug. The final four visits are the actual study days. Subjects will be randomly assigned (like the flip of a coin) to the different ways to get either 1) study medication or placebo (placebo contains no active study medication) and then 2) methamphetamine or placebo. Subjects will be in all four groups during the study, which means that each day a subject will get a different group.

Conditions

Methamphetamine Dependence

Keywords

Entacapone; COMT val158met; Methamphetamine

Outcome Measures

Primary Outcomes (3)

• Effect of Entacapone on Methamphetamine-induced Mood

  Profile of Mood States is a 65 item questionnaire using a Likert rating scale to assess transient, distinct moods. The questionnaire contains 65 words/statements that describe feelings people have. The test requires you to indicate for each word or statement how you have been feeling in the past week including today. A Total Mood Disturbance score is calculated by adding scores for Tension, Depression, Anger, Fatigue and Confusion and then subtracting the Vigour score. The Total Mood Disturbance scale ranges from -32 to 200 with lower scores indicative of people with more stable mood profiles.

  Measurements acquired before drug ingestion (baseline) then hourly for 4 hours. The peak interaction effect of entacapone and methamphetamine occurs 1 hour after ingestion, therefore the reported values are from this timepoint.

• Effect of Entacapone on Subjective Effects of Methamphetamine

  The subjective effects of the study drug were evaluated with the Addiction Research Center Inventory (ARCI-49), a 49 item questionnaire consisting of true/false items. True items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. There are 5 subscales: Morphine Benzedrine group scale to measure euphoria (range: 0-16 with higher numbers indicating more euphoria), A Lysergic Acid Diethylamide group scale to estimate dysphoria and agitation (range: 0-14 with higher scores indicating more dysphoria), a Pentobarbital Chlorpromazine Alcohol group scale to measure sedation (range: 0-15 with higher scores indicating more sedation), and a Benzedrine group scale and an Amphetamine Scale to assess stimulant effects (range: 0-13 and 0-11, respectively, with higher scores indicating higher stimulant effects) .

  Measurements acquired before drug ingestion (baseline) then hourly for 4 hours. The peak interaction effect of entacapone and methamphetamine occurs 1 hour after ingestion, therefore the reported values are from this timepoint.

• Effect of Entacapone on Methamphetamine-induced Stimulation

  The Global Rating of Stimulation is a 1-item question "I feel light-headed, restless, or speeded-up" in which the participant is asked to circle one answer on a scale from 0-4, 0 is 'normal', 1 is 'slightly', 2 is 'moderately', 3 is 'very much', and 4 is 'extremely'. Whichever number they circled is their reported score. A higher score is indicative of a greater stimulating effect.

  Measurements acquired before drug ingestion (baseline) then hourly for 4 hours. The peak interaction effect of entacapone and methamphetamine occurs 1 hour after ingestion, therefore the reported values are from this timepoint.

Secondary Outcomes (1)

• Cognitive Function

  Measurements acquired before drug ingestion (baseline) then hourly for 4 hours. The peak interaction effect of entacapone and methamphetamine occurs 1 hour after ingestion, therefore the reported values are from this timepoint.

Study Arms (4)

Placebo followed by Placebo

PLACEBO COMPARATOR

Subjects will receive placebo, then one hour later, placebo

Drug: Placebo

Placebo followed by Methamphetamine

EXPERIMENTAL

Subjects will receive placebo, then one hour later, methamphetamine

Drug: Methamphetamine; Drug: Placebo

Entacapone followed by Placebo

EXPERIMENTAL

Subjects will receive entacapone, then one hour later, placebo

Drug: Entacapone; Drug: Placebo

Entacapone followed by Methamphetamine

EXPERIMENTAL

Subjects will receive entacapone, then one hour later, methamphetamine

Drug: Entacapone; Drug: Methamphetamine

Interventions

Entacapone DRUG

Entacapone 200 mg oral dose

Also known as: Comtam

Entacapone followed by Methamphetamine; Entacapone followed by Placebo

Methamphetamine DRUG

Methamphetamine 20 mg oral dose

Also known as: Desoxyn

Entacapone followed by Methamphetamine; Placebo followed by Methamphetamine

Placebo DRUG

capsules compounded to be of similar appearance to the active drugs

Entacapone followed by Placebo; Placebo followed by Methamphetamine; Placebo followed by Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No history of pre-existing physical (including cardiovascular) illness
• No history of drug abuse or dependence
• Ability to read and write English
• Have had at least one exposure to a stimulant (e.g. cocaine, methamphetamine, ecstasy, methylphenidate or any medication in the stimulant class) in their lifetime

You may not qualify if:

• Pregnant
• Taking any psychotropic medication
• Meeting DSM-IV criteria for active substance abuse or dependence
• On any stimulant medication
• History or current hypertension (BP \> 140/90 mm Hg) or systolic hypotension (SBP \< 90 mm Hg)
• Subjects with resting pulse rate \> 90/min
• Any active medical illness
• Family history of abnormal heart rhythms, or sudden cardiac death
• Subjects who anticipate they may require the emergent use of epinephrine (such as an Epi-Pen®) for the treatment of severe allergic reactions

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Portland VA Medical Center: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Interventions

entacapone; Methamphetamine

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. William Hoffman
• Organization: Veterans Affairs Portland Healthcare System

hoffmanw@ohsu.edu

503-220-8262

Study Officials

• Jonathan C Fellers, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

• William F Hoffman, MD, PhD

  VA Portland Healthcare System

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 11, 2014
• Study Start: June 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: September 12, 2019
• Results First Posted: September 12, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)