Naltrexone + Bupropion for Methamphetamine Addiction

Recruiting in Palo Alto (17 mi)

+9 other locations

Overseen by Shwe Gyaw, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Tricyclics, MAOIs, Stimulants, others

Disqualifiers: Epilepsy, Heart block, Hypertension, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

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. ^{1 2 3 4 5}

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. ^{1 2 4 5 6}

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. ^{2 5 7 8 9}

Research Team

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.

Trial 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 (Other)

Trial Overview The 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

Group I: XR-NTX/BUP-XL Experimental Treatment 2 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/PLB Placebo Group 2 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)

🇪🇺 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

Research Locations Nearby Select from list below to view details:

University of Arkansas for Medical Sciences Little Rock, AR

Indiana University Indianapolis, IN

University of Minnesota Minneapolis, MN

University of Texas Southwestern Medical Center Dallas, TX

More Trial Locations

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2658

Patients Recruited

3,409,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. [2018] To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

2. United States pubmed.ncbi.nlm.nih.gov

Bupropion and Naltrexone in Methamphetamine Use Disorder. [2021] The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.

3. Ireland pubmed.ncbi.nlm.nih.gov

Methamphetamine/amphetamine use over time among persons with opioid use disorders treated with buprenorphine/naloxone versus extended-release naltrexone. [2022] Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use.

4. England pubmed.ncbi.nlm.nih.gov

Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats. [2019] This study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than either drug alone.

5. United States pubmed.ncbi.nlm.nih.gov

Naltrexone plus bupropion reduces cigarette smoking in individuals with methamphetamine use disorder: A secondary analysis from the CTN ADAPT-2 trial. [2023] Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Dissolution Assay of Bupropion/Naltrexone Hydrochloride Salts of Bilayer Composition Tablets Following the Development and Validation of a Novel HPLC Method. [2022] Compounded medicinal products containing bupropion hydrochloride (BUP·HCl) and naltrexone hydrochloride (NTX·HCl) are available as adjunct therapy for the management of weight in obese/overweight adults. The present work describes the development and validation of a novel RP-HPLC method for a simultaneous quantitation during the dissolution of both drugs from compounded bilayer composition tablets. The method involves a Nucleosil 100-3 C-18 column (4.6 × 150 mm) and a mobile phase of a 70%/30% v/v ACN/KH2PO4·H2O aqueous solution of a 5 mM concentration. The flow rate was set at 1.35 mL/min and the detection was conducted using UV spectrophotometry (λmax 214 nm). The method was validated according to the ICH guidelines and fulfilled the specifications for the specificity, linearity, accuracy, precision and stability for both the sample and standard solutions. Furthermore, the robustness of the method was evaluated by applying a fractional factorial experimental design and by utilizing both graphical and statistical approaches to identify the HPLC factors that should be strictly controlled during the analysis. The method proved to be suitable for the analysis of the dissolution samples and, consequently, the release of BUP·HCl and NTX·HCl from the formulations.

7. Netherlands pubmed.ncbi.nlm.nih.gov

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] This 2-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone + bupropion as a pharmacotherapy for methamphetamine (MA) use disorder.

8. United States pubmed.ncbi.nlm.nih.gov

Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine. [2018] Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of good effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use.

9. Ireland pubmed.ncbi.nlm.nih.gov

Bupropion for the treatment of methamphetamine dependence in non-daily users: a randomized, double-blind, placebo-controlled trial. [2022] Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users.