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.

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+

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion and Naltrexone in Methamphetamine Use Disorder. Trivedi, MH., Walker, R., Ling, W., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats. Nicholson, ER., Dilley, JE., Froehlich, JC.[2019]

NCBI (Pubmed)

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. Schmitz, JM., Stotts, AL., Yoon, JH., et al.[2023]

NCBI (Pubmed)

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. Apostolidi, A., Protopapa, C., Siamidi, A., et al.[2022]

In a pilot study involving 49 participants with severe methamphetamine use disorder, the combination of naltrexone and bupropion showed potential efficacy, with 11 participants meeting the predefined responder criteria for treatment success.

The study's design indicated that while the combination therapy did not meet the statistical success threshold of 9 responders, the results suggest enough promise to justify further investigation into this pharmacotherapy approach.

NCBI (Pubmed)

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. Mooney, LJ., Hillhouse, MP., Thomas, C., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine. Stoops, WW., Pike, E., Hays, LR., et al.[2018]

In a study involving 204 participants with methamphetamine dependence, bupropion did not significantly improve abstinence rates compared to a placebo, indicating it may not be effective for less-than-daily users of methamphetamine.

Despite 47% of participants adhering to the bupropion treatment protocol, the lack of difference in abstinence rates suggests that psychosocial therapy remains the primary treatment for methamphetamine dependence, and further research is needed to identify subgroups that might benefit from bupropion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion for the treatment of methamphetamine dependence in non-daily users: a randomized, double-blind, placebo-controlled trial. Anderson, AL., Li, SH., Markova, D., et al.[2022]

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]

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

Bupropion and Naltrexone in Methamphetamine Use Disorder. [2021]

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]

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

Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats. [2019]

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]

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]

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]

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

Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine. [2018]

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]