Intermittent Naltrexone Among Polysubstance Users (Project iN)

Naltrexone, a µ-opioid receptor antagonist, is a promising agent for methamphetamine-using and binge-drinking men who have sex with men (MSM). Naltrexone has shown efficacy in reducing relapse to amphetamines and is FDA-approved for alcohol dependence. Oral naltrexone is inexpensive and has few toxicities but the standard daily regimen for naltrexone is problematic as patients forget to take the medication. Given the challenges in daily dosing, alternate regimen schedules have been proposed to increase efficacy and expand the population that may benefit from this pharmacologic agent. One approach is intermittent targeted administration of naltrexone, whereby individuals take the medication as-needed in anticipation of substance use or during periods of craving. Administration of naltrexone prior to exposure to amphetamines significantly attenuates craving and targeted naltrexone has shown efficacy in reducing heavy alcohol use. However, there have been no studies assessing intermittent targeted dosing of naltrexone among methamphetamine-using and binge-drinking MSM. Polysubstance use patterns are common among MSM, and studies among those who abuse more than one substance are urgently needed. The aims of this study are to determine whether targeted dosing of naltrexone is feasible, tolerable and acceptable among non-dependent methamphetamine-using and binge-drinking MSM.

Study Overview

• Status: Completed
• Conditions: Methamphetamine; Alcohol
• Intervention / Treatment: Drug: Placebo; Drug: Intermittent Oral Naltrexone

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94102
      • San Francisco Department of Public Health, Substance Use Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. male gender or transgender male-to-female
2. self-reported anal sex with men in the prior six months while under the influence of meth and/or alcohol
3. self-reported meth use at least bi-weekly in the prior three months
4. at least weekly binge drinking (five or more drinks on a single drinking session) in the prior three months

4) interested in reducing meth use and/or binge drinking 5) HIV-negative by rapid test or medical record of HIV infection 6) no current acute illnesses requiring prolonged medical care 7) no chronic illnesses that are likely to progress clinically during trial participation 8) able and willing to provide informed consent and adhere to visit schedule 9) age 18-70 years 10) baseline complete blood count (CBC), total protein, albumin, glucose, alkaline phosphatase, creatinine, blood urea nitrogen (BUN), and electrolytes without clinically significant abnormalities as determined by study clinician in conjunction with symptoms, physical exam, and medical history

Exclusion Criteria:

1. any psychiatric (e.g., depression with suicidal ideation) or medical condition that would preclude safe participation in the protocol
2. known allergy or previous adverse reaction to naltrexone
3. current use of or dependence on any opioids or a known medical condition which currently requires or may likely require opioid analgesics
4. opioid-positive urine test at enrollment
5. current cluster of differentiation 4 (CD4) count < 200 cells/mm3
6. moderate or severe liver disease (aspartate aminotransferase, alanine aminotransferase, or total bilirubin > 3 times upper limit of normal)
7. impaired renal function (creatinine clearance < 60 ml/min)
8. currently participating in another research study
9. meth or alcohol dependence as determined by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) criteria
10. any condition that, in the principal investigator and/or study clinician's judgment interferes with safe participation or adherence to study procedures.
11. unwillingness to provide minimum locator for information
12. not having a cellular phone that can send or receive a text message
13. plans to leave the Bay Area during study follow-up
14. not comfortable speaking and reading English, enough to participate in a program in English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Naltrexone; Intermittent oral naltrexone to be taken on an as-needed basis for 8 weeks.	Drug: Intermittent Oral Naltrexone
PLACEBO_COMPARATOR: Placebo; Intermittent oral placebo to be taken on an as-needed basis for 8 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Retaining Participants in Trial	Proportion of persons retained by study arm.	proportions eligible and enrolled assessed on ongoing basis throughout the study, proportion of visits completed assessed bi-weekly for each participant; overall retention assessed over 2 month follow-up for each participant
Acceptability to Taking Medication	Mean number of pills taken weekly, as determined by recorded openings from an electronic monitoring device for study medication pill dispensers	2 month follow-up
Tolerability to Study Drug, as Measured by Adverse Events	Frequency of Adverse Events, by arm	2 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Glenn-Milo Santos, PhD, University of California, San Francisco; Study Director: Jason Euren, MA, San Francisco Department of Public Health

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: November 2, 2012
• First Submitted That Met QC Criteria: November 5, 2012
• First Posted (ESTIMATE): November 7, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: HIV; alcohol; methamphetamine; sexual behavior
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 12-09809; R36DA035109-01 (NIH)