360 Participants Needed
National Institute on Drug Abuse (NIDA) logo

Naltrexone + Bupropion for Methamphetamine Addiction

Recruiting in Indianapolis (>99 mi)
+9 other locations
JW
JD
RA
RC
AO
TC
Overseen ByTara Chowdhury, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: National Institute on Drug Abuse (NIDA)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the efficacy of extended release naltrexone plus bupropion XL (XR-NTX/BUP-XL) compared to matched injectable and oral placebo (iPLB/oPLB) in reducing methamphetamine (MA) use in individuals with moderate or severe methamphetamine use disorder (MUD) seeking to stop or reduce MA use.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot be on tricyclic antidepressants, certain asthma medications, some steroids, and other drugs that might interact with the study medications. It's best to discuss your current medications with the study team to see if any changes are needed.

What data supports the effectiveness of the drug combination of naltrexone and bupropion for methamphetamine addiction?

Research shows that the combination of naltrexone and bupropion can help reduce methamphetamine use and cigarette smoking in people with methamphetamine addiction, as seen in the ADAPT-2 trial.12345

Is the combination of Naltrexone and Bupropion generally safe for humans?

Research has shown that the combination of naltrexone and bupropion has been used safely in humans for conditions like smoking cessation and weight management. However, specific safety data for methamphetamine addiction is limited.12456

How is the drug combination of naltrexone and bupropion unique for treating methamphetamine addiction?

The combination of naltrexone and bupropion is unique because it targets both methamphetamine addiction and the common co-occurring issue of tobacco smoking, potentially improving overall treatment outcomes. This dual approach is not well-studied for methamphetamine use disorder, making it a novel option compared to other treatments.25789

Research Team

SG

Shwe Gyaw, MD

Principal Investigator

NIDA/NIH

Eligibility Criteria

This trial is for adults aged 18-65 with moderate to severe methamphetamine use disorder who want to reduce or stop using. Participants must have tested positive for methamphetamine twice, be willing to follow study procedures and medication instructions, and use a smartphone app for daily video dosing. Women of childbearing potential must agree to birth control measures.

Inclusion Criteria

I agree to use a smartphone app for daily medication videos.
I have provided at least 2 positive urine tests for methamphetamine.
I am between 18 and 65 years old.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive extended-release naltrexone injections and bupropion XL tablets or placebo for 12 weeks

12 weeks
4 visits (in-person) for injections at Weeks 1, 4, 7, and 10

Evaluation

Participants undergo urine drug screen tests to evaluate methamphetamine use reduction

2 weeks
4 visits (in-person) for urine drug screens

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
2 visits (in-person) at Weeks 14 and 16

Treatment Details

Interventions

  • Naltrexone/Bupropion
Trial OverviewThe trial tests if extended-release naltrexone combined with bupropion XL (XR-NTX/BUP-XL) is more effective than placebo in reducing methamphetamine use among individuals seeking treatment. It compares the drug combination against matched injectable and oral placebos.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: XR-NTX/BUP-XLExperimental Treatment2 Interventions
Participants randomized to the (XR-NTX/BUP-XL) arm will receive 450 mg of once-daily oral extended-release bupropion tablets and once every three weeks (Weeks 1, 4, 7, and 10) injections of extended-release naltrexone (Vivitrol®)
Group II: PLB/PLBPlacebo Group2 Interventions
Participants randomized to the PLB arm will receive once-daily placebo tablets and once every three weeks (Weeks 1, 4, 7, and 10) placebo injections.

Naltrexone/Bupropion is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Vivitrol (naltrexone) / Wellbutrin (bupropion) for:
  • Alcohol dependence (naltrexone)
  • Major depressive disorder (bupropion)
  • Seasonal affective disorder (bupropion)
  • Smoking cessation (bupropion)
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Approved in European Union as Vivitrol (naltrexone) / Wellbutrin (bupropion) for:
  • Alcohol dependence (naltrexone)
  • Major depressive disorder (bupropion)
  • Seasonal affective disorder (bupropion)
  • Smoking cessation (bupropion)

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials
2,658
Recruited
3,409,000+

Findings from Research

In a study involving 302 participants with cocaine dependence and a history of opioid dependence, buprenorphine + naloxone (BUP) combined with extended-release injectable naltrexone (XR-NTX) showed a significant reduction in cocaine use for those receiving 16 mg/day of BUP compared to placebo, indicating its potential effectiveness in this population.
However, no significant differences were observed in the primary outcome for the 4 mg/day BUP group compared to placebo, suggesting that higher doses may be necessary for efficacy, while adherence, retention, and adverse events were similar across all groups.
Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study.Ling, W., Hillhouse, MP., Saxon, AJ., et al.[2018]
In a trial involving 403 adults with methamphetamine use disorder, the combination of extended-release injectable naltrexone and oral bupropion showed a higher response rate (13.6%) compared to placebo (2.5%) over 12 weeks, indicating some efficacy in reducing methamphetamine use.
While the treatment was more effective than placebo, the overall response rate was still low, and adverse events such as gastrointestinal issues and tremors were reported in some participants, highlighting the need for careful monitoring during treatment.
Bupropion and Naltrexone in Methamphetamine Use Disorder.Trivedi, MH., Walker, R., Ling, W., et al.[2021]
In a study of 570 patients with opioid use disorder (OUD) treated for 24 weeks, 18.4% reported methamphetamine/amphetamine (MA/A) use at baseline, and this usage did not significantly decline over time.
While there was no significant difference in MA/A use between those treated with buprenorphine/naloxone (BUP-NX) and extended-release naltrexone (XR-NTX), BUP-NX subjects had about half the odds of MA/A use compared to XR-NTX, suggesting a potential benefit that warrants further research.
Methamphetamine/amphetamine use over time among persons with opioid use disorders treated with buprenorphine/naloxone versus extended-release naltrexone.Tsui, JI., Campbell, ANC., Pavlicova, M., et al.[2022]

References

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. [2018]
Bupropion and Naltrexone in Methamphetamine Use Disorder. [2021]
Methamphetamine/amphetamine use over time among persons with opioid use disorders treated with buprenorphine/naloxone versus extended-release naltrexone. [2022]
Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats. [2019]
Naltrexone plus bupropion reduces cigarette smoking in individuals with methamphetamine use disorder: A secondary analysis from the CTN ADAPT-2 trial. [2023]
Dissolution Assay of Bupropion/Naltrexone Hydrochloride Salts of Bilayer Composition Tablets Following the Development and Validation of a Novel HPLC Method. [2022]
Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder. [2019]
Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine. [2018]
Bupropion for the treatment of methamphetamine dependence in non-daily users: a randomized, double-blind, placebo-controlled trial. [2022]