Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine Use Disorder

NCT ID: NCT03078075

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 403 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-05
• Study Completion Date: 2019-07-25

Brief Summary

This is a double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy of extended-release naltrexone plus bupropion as a combination pharmacotherapy for methamphetamine use disorder. Participants will be randomly assigned to the active medication combination (AMC) group or matching placebo group and will receive medications over the course of 12 weeks. Follow-ups will occur in weeks 13 and 16.

Detailed Description

There will be 400 adults with moderate or severe methamphetamine use disorder randomized into this multi-site study. Eligibility will be determined during a maximum 21 day screening period. After screening is completed and eligibility is confirmed, including successful administration of a naloxone challenge, participants will begin the 12 week medication phase of the trial. Participants will be randomized to either the 1) AMC arm and receive injections of extended release naltrexone (XR-NTX; as Vivitrol®) plus once-daily oral extended-release bupropion tablets (BUP-XL) or the 2) matching placebo (PLB) arm and receive injections of placebo (iPLB) plus once-daily oral placebo (oPLB) tablets. During the course of the study, participants may be switched to another arm, as determined by the a priori adaptive aspect of the study design. Participants appearing to respond well to their original treatment assignment will not be switched. Overall, approximately 50% of the participants will receive the AMC. Injections will be administered every three weeks, in weeks 1, 4, 7, and 10. Take-home oral study medication (BUP-XL or oPLB) will be dispensed weekly for dosing on non-clinic days. Participants will be asked to attend the clinic twice weekly for observed oral medication dosing, assessments, collection of urine samples, and once-weekly medical management. On non-clinic days, participants will participate in smartphone app-based medication adherence activities. Participants will be asked to complete assessments as indicated on the schedule of assessments. Following the 12 week medication phase, participants will complete a follow-up phase, including a medication taper and post-medication phase follow-up visits during weeks 13 and 16.

Conditions

Methamphetamine Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Medication Combination (AMC)

injectable extended release naltrexone plus once daily oral extended-release bupropion tablets

Group Type: EXPERIMENTAL

Naltrexone: Vivitrol®

Intervention Type: DRUG

Naltrexone: 380 mg vial, 4 intramuscular injections administered every 3 weeks

Bupropion: Wellbutrin XL®

Intervention Type: DRUG

Bupropion: 450 mg oral dose daily

Matched Placebo (PLB)

injectable matching placebo plus once-daily oral placebo tablets

Group Type: PLACEBO_COMPARATOR

Placebo (PLB) Injectable

Intervention Type: DRUG

Placebo: 4 intramuscular injections administered every 3 weeks

Placebo (PLB) Oral

Intervention Type: DRUG

Placebo: once-daily oral placebo tablets

Interventions

Naltrexone: Vivitrol®

Naltrexone: 380 mg vial, 4 intramuscular injections administered every 3 weeks

Intervention Type: DRUG

Placebo (PLB) Injectable

Placebo: 4 intramuscular injections administered every 3 weeks

Intervention Type: DRUG

Bupropion: Wellbutrin XL®

Bupropion: 450 mg oral dose daily

Intervention Type: DRUG

Placebo (PLB) Oral

Placebo: once-daily oral placebo tablets

Intervention Type: DRUG

Other Intervention Names

Arm: Experimental - Active Medication Combination (AMC); Injectable matching (to Naltrexone) placebo; Arm: Placebo Comparator - matched Placebo (PLB); Arm: Experimental - Active Medication Combination (AMC); Oral matching (to Bupropion) placebo tablets; Arm: Placebo Comparator - matched Placebo (PLB)

Eligibility Criteria

Inclusion Criteria

• 18 to 65 years old;
• Interested in reducing/stopping methamphetamine use;
• Speak English;
• Agree to use acceptable birth control (if applicable);
• Be opioid-free at randomization;
• Willing to comply with all study procedures and medication instructions;
• Agree to use a cell phone (or similar study device) to take videos of medication dosing.

Exclusion Criteria

• Medical or psychiatric condition which would make participation unsafe;
• Recently participated in a study of pharmacological or behavioral treatment for methamphetamine use disorder;
• Recently taken an investigational drug;
• Prescribed and taken naltrexone or bupropion ≤ 30 days from consent;
• Current or planned extended absence during study period (e.g., jail, surgery, pending legal action);
• Currently pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Madhukar H. Trivedi, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Madhukar Trivedi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

University of California Los Angeles (UCLA) Center for Behavioral Addiction Medicine (CBAM)

Los Angeles, California, United States

Substance Use Research Unit (SURU) at the San Francisco Dept. of Public Health

San Francisco, California, United States

Hennepin County Medical Center- Berman Center for Research

Minneapolis, Minnesota, United States

New York State Psychiatric Institute (NYSPI)- Substance Use Research Center (SURC)

New York, New York, United States

CODA, Inc.

Portland, Oregon, United States

Behavioral Health Services (BHS) of Pickens County

Pickens, South Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Texas Health Science Center - Center for Neurobehavioral Research on Addiction (CNRA)

Houston, Texas, United States

Countries

United States

References

Jha MK, Ghitza UE, Shoptaw S, Minhajuddin A, Kuruvila S, Wakhlu S, Nunes EV, Schmitz J, Coffin PO, Bart G, Carmody T, Trivedi MH. Early Change in Depressive Symptom Severity With Naltrexone-Bupropion Combination and Its Association With Reduction in Methamphetamine Use in ADAPT-2 Trial. J Clin Psychiatry. 2025 Jul 30;86(3):25m15825. doi: 10.4088/JCP.25m15825.

Reference Type: DERIVED

PMID: 40767786 (View on PubMed)

Okafor CN, Carmody T, Stotts AL, Bart G, Mayes TL, Karns-Wright T, Trivedi M, Shoptaw S, Potter JS. Sociodemographic and patient reported outcomes by racial and ethnicity status among participants in a randomized controlled trial for methamphetamine use disorder. Drug Alcohol Depend Rep. 2024 Apr 6;11:100230. doi: 10.1016/j.dadr.2024.100230. eCollection 2024 Jun.

Reference Type: DERIVED

PMID: 38665252 (View on PubMed)

Trombello JM, Kulikova A, Mayes TL, Nandy K, Carmody T, Bart G, Nunes EV, Schmitz J, Kalmin M, Shoptaw S, Trivedi MH. Psychometrics of the Concise Health Risk Tracking Self-Report (CHRT-SR16) Assessment of Suicidality in a Sample of Adults with Moderate to Severe Methamphetamine Use Disorder: Findings from the ADAPT-2 Randomized Trial. Neuropsychiatr Dis Treat. 2023 Jun 22;19:1443-1454. doi: 10.2147/NDT.S406909. eCollection 2023.

Reference Type: DERIVED

PMID: 37377462 (View on PubMed)

Vo HT, Kulikova A, Mayes TL, Carmody T, Shoptaw S, Ling W, Trombello JM, Trivedi MH. Psychometric properties of the Treatment Effectiveness Assessment in methamphetamine use disorder. J Subst Use Addict Treat. 2023 Aug;151:209085. doi: 10.1016/j.josat.2023.209085. Epub 2023 May 26.

Reference Type: DERIVED

PMID: 37245855 (View on PubMed)

Trivedi MH, Walker R, Ling W, Dela Cruz A, Sharma G, Carmody T, Ghitza UE, Wahle A, Kim M, Shores-Wilson K, Sparenborg S, Coffin P, Schmitz J, Wiest K, Bart G, Sonne SC, Wakhlu S, Rush AJ, Nunes EV, Shoptaw S. Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021 Jan 14;384(2):140-153. doi: 10.1056/NEJMoa2020214.

Reference Type: DERIVED

PMID: 33497547 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

UG1DA020024

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CTN-0068

Identifier Type: -

Identifier Source: org_study_id