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

NCT03078075 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CTN-0068UG1DA020024
• Study Type: interventional
• Target: 403
• Locations: 1 country
• Sites: 8

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.

Conditions

Methamphetamine Use Disorder

Keywords

Methamphetamine; Methamphetamine Use Disorder; Naltrexone; Bupropion; Vivitrol®

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Response During Medication Phase at Stage 1

  Treatment response is defined as 'Responder' and 'Non-Responder'. Responder : Participant who meet responder criterion by providing at least 3 out of a possible 4 methamphetamine-negative urine tests at the end of stage 1 (weeks 5-6). Non-Responder: All other participants without 3 or 4 methamphetamine-negative UDS (Urine Drug Screen).

  At weeks 6

• Number of Participants With Treatment Response During Medication Phase at Stage 2

  Treatment response is defined as 'Responder' and 'Non-Responder'. Responder : Participant who meet responder criterion by providing at least 3 out of a possible 4 methamphetamine-negative urine tests at the end of stage 1 (weeks 5-6). Non-Responder: All other participants without 3 or 4 methamphetamine-negative UDS.

  At week 12

Secondary Outcomes (27)

• Treatment Effectiveness Score of Participants at Stage 1

  At weeks 6

• Treatment Effectiveness Score of Participants at Stage 2

  At week 12

• Percentage of Participants Who Used Methamphetamine in the Pre-evaluation Period

  Weeks 1-4 and Weeks 7-10

• Mean Maximum Number of Consecutive Visits Negative UDS at Stage 1

  At week 6

• Mean Maximum Number of Consecutive Visits Negative UDS at Stage 2

  Stage 2 evaluation period at Weeks 12

Study Arms (2)

Active Medication Combination (AMC)

EXPERIMENTAL

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

Drug: Naltrexone: Vivitrol®; Drug: Bupropion: Wellbutrin XL®

Matched Placebo (PLB)

PLACEBO COMPARATOR

injectable matching placebo plus once-daily oral placebo tablets

Drug: Placebo (PLB) Injectable; Drug: Placebo (PLB) Oral

Interventions

Naltrexone: Vivitrol® DRUG

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

Also known as: Arm: Experimental - Active Medication Combination (AMC)

Active Medication Combination (AMC)

Placebo (PLB) Injectable DRUG

Placebo: 4 intramuscular injections administered every 3 weeks

Also known as: Injectable matching (to Naltrexone) placebo, Arm: Placebo Comparator - matched Placebo (PLB)

Matched Placebo (PLB)

Bupropion: Wellbutrin XL® DRUG

Bupropion: 450 mg oral dose daily

Also known as: Arm: Experimental - Active Medication Combination (AMC)

Active Medication Combination (AMC)

Placebo (PLB) Oral DRUG

Placebo: once-daily oral placebo tablets

Also known as: Oral matching (to Bupropion) placebo tablets, Arm: Placebo Comparator - matched Placebo (PLB)

Matched Placebo (PLB)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (8)

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

Los Angeles, California, 90038, United States

Location

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

San Francisco, California, 94102, United States

Location

Hennepin County Medical Center- Berman Center for Research

Minneapolis, Minnesota, 55415, United States

Location

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

New York, New York, 10032, United States

Location

CODA, Inc.

Portland, Oregon, 97214, United States

Location

Behavioral Health Services (BHS) of Pickens County

Pickens, South Carolina, 29671, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

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

Houston, Texas, 77054, United States

Location

Related Publications (5)

• 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.

  PMID: 40767786 DERIVED

• 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.

  PMID: 38665252 DERIVED

• 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.

  PMID: 37377462 DERIVED

• 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.

  PMID: 37245855 DERIVED

• 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.

  PMID: 33497547 DERIVED

MeSH Terms

Interventions

phospholamban; Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Madhukar Trivedi
• Organization: UT Southwestern Medical Center

Madhukar.Trivedi@UTSouthwestern.edu

214/648-0188

Study Officials

• Madhukar Trivedi, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: During the study, participants may or may not be switched to another group due to the adaptive aspect of the study design. Participants appearing to respond well to their original treatment assignment will not be switched.

Study Record Dates

• First Submitted: March 2, 2017
• First Posted: March 13, 2017
• Study Start: May 5, 2017
• Primary Completion: July 3, 2019
• Study Completion: July 25, 2019
• Last Updated: May 3, 2021
• Results First Posted: March 29, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8)