Using Naltrexone and Bupropion to Treat Methamphetamine Addiction

Randomized, Placebo-Controlled, Multi-Site Trial of Extended-Release Naltrexone Injection/Bupropion XL Tablets in the Treatment of Methamphetamine Use Disorder

This study is testing if a combination of two medications can help people with methamphetamine addiction reduce their drug use over 12 weeks.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: National Institute on Drug Abuse (NIDA) (NIH)
• Locations: 11 sites (Little Rock, Arkansas and 10 other locations)
• Trial ID: NCT06233799 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of extended release naltrexone combined with bupropion XL in reducing methamphetamine use among individuals with moderate to severe methamphetamine use disorder. The study involves 360 participants who will be randomly assigned to receive either the active medication combination or a placebo for a 12-week treatment period. The primary outcome is the number of participants achieving at least three negative urine drug screens for methamphetamine during the final weeks of treatment. Secondary outcomes include assessments of safety, substance use, depression, quality of life, and medication adherence.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 who meet the criteria for moderate or severe methamphetamine use disorder and are motivated to reduce or stop their methamphetamine use.

Not a fit: Patients who are physically dependent on opioids or do not meet the criteria for moderate or severe methamphetamine use disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for individuals struggling with methamphetamine addiction.

How similar studies have performed: Other studies have explored similar pharmacological approaches for substance use disorders, but this specific combination of naltrexone and bupropion for methamphetamine use disorder is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Is 18 to 65 years of age;
2. Meets DSM-5 criteria for moderate or severe MUD (4 or more criteria);
3. Is interested in reducing or stopping MA use;
4. Is able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study;
5. Self-reports MA use on 18 or more days in the 30-day period prior to consent using the Timeline Followback (TLFB);
6. Provides at least 2 urine samples positive for MA out of up to 3 tests, which will occur at least 2 days apart within a 10-day period;
7. If assigned as female at birth and/or currently has a uterus, is not pregnant, agrees to use acceptable birth control methods, and have periodic urine pregnancy testing done during participation in the study unless documentation of hysterectomy provided;
8. Is not physically dependent on opioids and meets subjective and objective measures of being opioid-free prior to naltrexone injection per study medical clinician's determination, including, if clinically required, a negative naloxone challenge;
9. Is willing to comply with all study procedures and medication instructions;
10. Agrees to use a smartphone app (downloaded for free to own device or on a study provided smartphone device) to take daily videos of medication dosing.

Exclusion Criteria:

1. Has an acute medical or psychiatric disorder that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
2. Has suicidal or homicidal ideation that requires immediate attention;
3. Has a history of epilepsy, seizure disorder, or head trauma with neurological sequelae (e.g., loss of consciousness that required hospitalization); current anorexia nervosa or bulimia; or any other conditions that increase seizure risk in the opinion of the study medical clinician;
4. Has evidence of second or third degree heart block, atrial fibrillation, atrial flutter, prolongation of the QTc, or any other finding on the screening ECG that, in the opinion of the study medical clinician, would preclude safe participation in the study;
5. Has Stage 2 hypertension as determined by the study medical clinician (e.g., greater than or equal to 160/100 in 2 out of 3 readings during screening);
6. Has any elevated bilirubin test value per laboratory criteria OR any other liver function test (LFT) value \> 5 times the upper limit of normal per laboratory criteria;
7. Has a platelet count \<100 x 10exp3/microliter;
8. Has a body habitus that precludes gluteal intramuscular injection of XR-NTX in accordance with the administration equipment (needle) and procedures;
9. Has a known allergy or sensitivity to bupropion, naloxone, naltrexone, PLG (polyactideco-glycolide), carboxymethylcellulose or any other component of the XR-NTX diluents;
10. Has been in a prior study of pharmacological or behavioral treatment for MUD within 6 months of study consent;
11. Has taken an investigational drug in another study within 30 days of study consent;
12. Has been prescribed and taken naltrexone or bupropion within 30 days of study consent;
13. Is concurrently enrolled in formal behavioral or pharmacological Substance Use Disorder (SUD) treatment services;
14. Is receiving ongoing treatment with tricyclic antidepressants, xanthines (i.e., theophylline and aminophylline), systemic corticosteroids, nelfinavir, efavirenz, chlorpromazine, MAOIs, central nervous system stimulants (e.g., Adderall, Ritalin, etc.), or any medication that, in the judgment of the study medical clinician, could interact adversely with study medications;
15. Has a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use which would preclude safe participation in the study as determined by the study medical clinician;
16. Requires treatment with opioid-containing medications (e.g., opioid analgesics) during the study period;
17. Has a surgery planned or scheduled during the study period;
18. Is currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that could prevent participation in the study or in any study activities;
19. If assigned as female at birth and/or currently has a uterus, is currently pregnant, breastfeeding, or planning on conception.

Where this trial is running

Little Rock, Arkansas and 10 other locations

• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (Recruiting)
• University of California Los Angeles — Los Angeles, California, United States (Recruiting)
• University of California at San Diego — San Diego, California, United States (Recruiting)
• Indiana University — Indianapolis, Indiana, United States (Recruiting)
• University of Kansas Medical Center — Kansas City, Kansas, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Coda — Portland, Oregon, United States (Recruiting)
• Musc/bhs — Pickens, South Carolina, United States (Recruiting)
• University of Tennessee — Memphis, Tennessee, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• University of Virginia — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Raul Mandler, MD — Nida/nih
• Study coordinator: Jennifer Wong, PhD

Conditions Methamphetamine-dependence; Methamphetamine Abuse