Risky Decision Making in Methamphetamine Users: The Role of Opioid Blockade

This study is currently recruiting participants.
Verified July 2013 by Oregon Health and Science University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
P. Todd Korthuis, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT01822132
First received: March 21, 2013
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

The purpose of this protocol is to learn more about impulsive decision making in people who use methamphetamines. The investigators would like to know if a medication called naltrexone changes how people make decisions. The investigators would also like to know whether changes in decision making can be observed by MRI (magnetic resonance imaging).


Condition Intervention
Methamphetamine Abuse
HIV
Drug: Extended release naltrexone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Risky Decision Making in Methamphetamine Users: The Role of Opioid Blockade

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Discounting Tasks [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Delay Discounting economic task that asks subjects to choose between an immediate reward and a second reward that varies in delay until receipt. Probes the neural mechanism of the effect of endogenous opioid blockade on impulsive choice in MA users.


Secondary Outcome Measures:
  • Neural Mapping [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    We expect to identify a map of regions for each component of delay discounting: delay magnitude, reward magnitude and choice. Our preliminary assignment of delay sensitivity to middle frontal gyrus may reflect magnitude sensitivity. This would suggest that discounting (calculation of the value of a delayed reward) is a separate cognitive function from representation of the magnitude of the alternative reward. We expect increased ventrolateral prefrontal and ventral striatal activity with increased immediate reward magnitude in the overall group. We expect increased medial prefrontal activity to scale with decreased delay magnitude, and for dorsal regions (inferior parietal lobule, insula, and dorsolateral prefrontal cortex) to exhibit more activity in Decision trials than No Decision trials.

  • Methamphetamine use [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Any methamphetamine use in the 28 days since injection of study drug or placebo, by self report and urine drug screen.

  • HIV risk behaviors [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Unprotected sex or sharing of needles/works in the 28 days since injection of study drug or placebo.

  • Antiretroviral adherence [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Any missed doses of antiretroviral medications in 28 days since injection of study drug or placebo, by self-report.


Estimated Enrollment: 50
Study Start Date: May 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Extended release naltrexone
One dose of intramuscular injection of 380mg extended-release naltrexone.
Drug: Extended release naltrexone
Other Name: Vivitrol
Placebo Comparator: Placebo
One dose of intramuscular injection of placebo.
Drug: Placebo

Detailed Description:

We propose a randomized placebo-controlled study of the effect of endogenous opioid blockade with extended release naltrexone (XR-NTX) on delay discounting and its neural substrate in methamphetamine (MA) users. Recently abstinent MA users recruited from the community and addiction treatment centers in Portland, Oregon will be assessed with fMRI (functional magnetic resonance imaging), delay discounting tasks, drug use, and HIV risk behaviors at baseline and 28-days following randomization.

AIM 1: Determine the neural basis of impulsive choice in MA users. This aim will identify brain regions that can be used to characterize the neural basis for impulsive choice in the proposed study sample. We will extend results of previous studies and our preliminary data to assess specific brain regions whose activity scales with magnitude of reward, length of delay and the act of making a decision. Aim 1 is essential for developing neural predictors hypothesized in Aim 2 to be more sensitive to and predictive of a clinical response to XR-NTX than behavioral measures alone.

Hypothesis 1.1: We hypothesize that activity (a) in ventral striatum (VS) and ventrolateral prefrontal cortex (VLPFC) will scale with magnitude of reward, (b) in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) with length of delay and (c) in anterior insula and the inferior parietal lobule (IPL) with the process of making a decision.

AIM 2: Assess the effect of endogenous opioid blockade on impulsivity and its neural substrate. We will build on Aim 1 findings to assess how endogenous opioid blockade with XR-NTX affects cortical decision-making.

Hypothesis 2.1: Subjects randomized to XR-NTX will show decreased impulsivity (preference for immediate rewards) from baseline compared to those randomized to placebo. Hypothesis 2.2: Subjects with the greatest decrements in impulsivity will exhibit decreased cerebral response to reward magnitude in VS and VLPFC and decreased response to length of delay in ACC and DLPFC. These effects will be more pronounced in the XR-NTX group.

AIM 3 (Exploratory): Examine the effect of endogenous opioid blockade on the association between risky behaviors and activity of the neural substrates of impulsive choice.

Hypothesis 3.1: Subjects with brain regions demonstrating robust responses to NTX will demonstrate the greatest decreases in MA use and HIV risk behaviors (e.g., unprotected sex, needle sharing).

AIM 4 (Exploratory): Assess the effect of endogenous opioid blockade on impulsivity and its neural substrate in HIV-infected methamphetamine users. Pending supplemental funding, we will enroll an additional 10 HIV-infected subjects who meet other inclusion and exclusion criteria to demonstrate the feasibility of conducting proposed study procedures in HIV-infected subjects.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnostic and Statistical Manual (DSM)-IV Methamphetamine Dependence
  • No other substance dependence except tobacco and/or nicotine dependence
  • No history of psychiatric disorder except depression and/or PTSD
  • Age 18-55
  • Right handed
  • English-speaking
  • Drug and alcohol free for at least 72 hours
  • Sexually active within the past 30 days
  • Caffeine and nicotine allowed up to 1 hr before fMRI
  • Aspartate transaminase (AST) & alanine aminotransferase (ALT) < 5x upper limit

Exclusion Criteria:

  • Current opioid use in the last 30 days; abuse or dependence within past 5 years
  • Known hypersensitivity to naltrexone, PLG (polylactide-co-glycolide) carboxymethylcellulose, or any other components of the diluent
  • Potential need for opioid analgesics during study period
  • Pregnancy
  • MRI contraindications (e.g. metal in head).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822132

Contacts
Contact: Sarann Bielavitz, BS 503-418-1944 bielavit@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Philip T Korthuis, MD, MPH         
Portland VA Medical Center Recruiting
Portland, Oregon, United States, 97239
Sub-Investigator: Willliam Hoffman, PhD, MD         
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Philip T Korthuis, MD, MPH Oregon Health and Science University
  More Information

No publications provided

Responsible Party: P. Todd Korthuis, Associate Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01822132     History of Changes
Other Study ID Numbers: ALKIIT-KOR-034, 1R21DA033182-01A1
Study First Received: March 21, 2013
Last Updated: July 23, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Naltrexone
Methamphetamine
Analgesics, Opioid
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Sympathomimetics
Autonomic Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Dopamine Uptake Inhibitors
Analgesics
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 16, 2014