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

• ClinicalTrials.gov Identifier: NCT01822132
• Recruitment Status: Completed
• First Posted: April 2, 2013
• Results First Posted: February 6, 2019
• Last Update Posted: March 5, 2019
• Sponsor: Oregon Health and Science University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): P. Todd Korthuis, MD, Oregon Health and Science University

Tracking Information

• First Submitted Date: March 21, 2013
• First Posted Date: April 2, 2013
• Results First Submitted Date: September 20, 2017
• Results First Posted Date: February 6, 2019
• Last Update Posted Date: March 5, 2019
• Study Start Date: May 2013
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2019)

• Discounting Tasks: Sexual Probability Discounting (SexPD) [ Time Frame: 28 days post drug intervention ]
  In the SexPD task, subjects are asked to choose between having sex with a more appealing partner with a varying chance of having a sexually transmitted infection (STI) or a less appealing partner with no STI. A hyperbolic decay model was used to calculate h, a free parameter that indexes the rate of probabilistic discounting. Smaller h values indicate a preference for probabilistic (i.e., riskier) outcomes. To normalize the data, the natural log of h values were calculated and reported here.
• Discounting Tasks: Standard Delay Discounting (DD) [ Time Frame: 28 days post drug intervention ]
  Monetary delay discounting task consisted of choosing between a larger, delayed and a smaller, immediate reward. A hyperbolic decay model was used to calculate k, a free parameter that indexes the rate of delay discounting. As k values are typically skewed across subjects, the distribution of k was normalized by using a natural log transformation. The normalized values are reported here. If k typically ranges between 0.5 and 10^-5, then the natural log of k will range between -0.69 and -11.5. Larger normalized k values indicate a preference for smaller sooner outcomes (i.e., more impulsive decision-making).
• Barrat Impulsiveness Scale (BIS) [ Time Frame: 28 days post drug intervention ]
  The Barrat Impulsiveness Scale (BIS) is a 30 item questionnaire to measure a persons impulsiveness. Items are answered on a 4-point scale and scored 1-4 then summed across responses. Total scores range from 30-120 with a higher summed score indicating higher impulsivity.
• Risk Assessment Battery (RAB) [ Time Frame: 28 days post drug intervention ]
  The Risk Assessment Battery (RAB) is a 26 question self-administered assessment focusing on drug use, injection and sexual risk during the past 30 days. Three composite HIV risk scores (drug, sex, and total score) are calculated. The questions have different numbers of items, and scores for a single question can range from 0 to 7, with higher values reflecting more instances of risk behavior. The drug risk score has a range of 0 to 22 and is calculated from 8 questions that address recent substance use, including frequency, needle sharing, and cleaning of the "works." 9 questions are used to calculate a sex risk score that has a range of 0 to 18, and these questions address the frequency and types of sexual behavior, HIV status of sexual partners, and type of protection that was used (if any). Total score is calculated by adding drug and sex scores and dividing by 40, the maximum score possible, and ranges from 0 to 40 where higher scores indicate greater risk behavior.

Original Primary Outcome Measures (submitted: March 27, 2013)

Discounting Tasks [ Time Frame: 28 days ]

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.

Current Secondary Outcome Measures (submitted: January 16, 2019)

Methamphetamine Use [ Time Frame: 28 days post drug intervention ]

Participants were asked "How many days in the past 30 days did you use methamphetamine?". This is a self-report measure.

Original Secondary Outcome Measures (submitted: March 27, 2013)

• Neural Mapping [ Time Frame: 28 days ]
  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 ]
  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 ]
  Unprotected sex or sharing of needles/works in the 28 days since injection of study drug or placebo.
• Antiretroviral adherence [ Time Frame: 28 days ]
  Any missed doses of antiretroviral medications in 28 days since injection of study drug or placebo, by self-report.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Risky Decision Making in Methamphetamine Users: The Role of Opioid Blockade
• Official Title: Risky Decision Making in Methamphetamine Users: The Role of Opioid Blockade

Brief Summary

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).

The research is conducted in Portland, OR.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Other

Condition

• Methamphetamine Abuse
• HIV

Intervention

• Drug: Extended release naltrexone
  Other Name: Vivitrol
• Drug: Placebo

Study Arms

• Experimental: Extended release naltrexone
  One dose of intramuscular injection of 380mg extended-release naltrexone.
  Intervention: Drug: Extended release naltrexone
• Placebo Comparator: Placebo
  One dose of intramuscular injection of placebo.
  Intervention: Drug: Placebo

Publications *

• Kohno M, Morales AM, Dennis LE, McCready H, Hoffman WF, Korthuis PT. Effects of Naltrexone on Large-Scale Network Interactions in Methamphetamine Use Disorder. Front Psychiatry. 2019 Sep 3;10:603. doi: 10.3389/fpsyt.2019.00603. eCollection 2019.
• Kohno M, Dennis LE, McCready H, Schwartz DL, Hoffman WF, Korthuis PT. A preliminary randomized clinical trial of naltrexone reduces striatal resting state functional connectivity in people with methamphetamine use disorder. Drug Alcohol Depend. 2018 Nov 1;192:186-192. doi: 10.1016/j.drugalcdep.2018.07.045. Epub 2018 Sep 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 16, 2019): 76
• Original Estimated Enrollment (submitted: March 27, 2013): 50
• Actual Study Completion Date: March 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Summary Inclusion Criteria:

• Diagnostic and Statistical Manual (DSM)-IV Methamphetamine Dependence
• Deemed healthy enough to participate by study physician
• Age 18-55
• Right handed
• English-speaking

Summary Exclusion Criteria:

• Current opioid use in the last 30 days; opioid abuse or dependence within past 5 years
• Pregnancy
• MRI contraindications (e.g. metal in head).

The research is conducted in Portland, OR.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01822132
• Other Study ID Numbers: ALKIIT-KOR-034; 1R21DA033182-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: P. Todd Korthuis, MD, Oregon Health and Science University
• Study Sponsor: Oregon Health and Science University
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Philip T Korthuis, MD, MPH; Oregon Health and Science University

• PRS Account: Oregon Health and Science University
• Verification Date: February 2019