Clinical trial NCT03078075: Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine Use Disorder
Official title: NIDA (National Institute on Drug Abuse) CTN (Clinical Trials Network) Protocol 0068: Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Methamphetamine Use Disorder
Keywords: Methamphetamine
Methamphetamine Use Disorder
Naltrexone
Bupropion
Vivitrol®
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: The Emmes Company, LLC
First posted: 2017-03-13
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Response During Medication Phase at Stage 1
timeFrame: At weeks 6
measure: Number of Participants With Treatment Response During Medication Phase at Stage 2
timeFrame: At week 12
Secondary outcomes:
measure: Treatment Effectiveness Score of Participants at Stage 1
timeFrame: At weeks 6
measure: Treatment Effectiveness Score of Participants at Stage 2
timeFrame: At week 12
measure: Percentage of Participants Who Used Methamphetamine in the Pre-evaluation Period
timeFrame: Weeks 1-4 and Weeks 7-10
measure: Mean Maximum Number of Consecutive Visits Negative UDS at Stage 1
timeFrame: At week 6
measure: Mean Maximum Number of Consecutive Visits Negative UDS at Stage 2
timeFrame: Stage 2 evaluation period at Weeks 12
measure: Mean Number of Study Weeks With Two Methamphetamine-negative UDS at Stage 1
timeFrame: At week 6
measure: Mean Number of Study Weeks With Two Methamphetamine-negative UDS at Stage 2
timeFrame: At week12
measure: Mean Change of Percentage of Methamphetamine Abstinent Days Measured by Self-report at Stage 1
timeFrame: Baseline, week 6
measure: Mean Change Percentage of Methamphetamine Abstinent Days Measured by Self-report at Stage 2
timeFrame: week 7, week 12
measure: Mean Change of Methamphetamine Craving at Stage 1
timeFrame: Baseline, week 6
measure: Mean Change of Methamphetamine Craving at Stage 2
timeFrame: week 7, week 12
measure: Mean Number of Abstinent Days of Participants Who Used Other Substance Measured by UDS at Stage 1
timeFrame: At week 6
measure: Mean Number of Abstinent Days of Participants Who Used Other Substance Measured by UDS at Stage 2
timeFrame: at week 12
measure: Mean Change of Proportion of Other Substance Abstinent Days Measured by Self-report at Stage 1
timeFrame: Baseline, week 6
measure: Mean Change of Proportion of Other Substance Abstinent Days Measured by Self-report at Stage 2
timeFrame: week 7, week 12
measure: Mean Change in Number of Other Substance Use by Self-report at Stage 1
timeFrame: Baseline, week 6
measure: Mean Change in Number of Other Substance Use by Self-report at Stage 2
timeFrame: week 7, week 12
measure: Change in Proportion of E-cigarettes Abstinent Days by Self-report at Stage 1
timeFrame: Baseline, week 6
measure: Change in Proportion of E-cigarettes Abstinent Days by Self-report at Stage 2
timeFrame: week 7, week 12
measure: Mean Change of Depression Symptom Score by PHQ-9 at Stage 1
timeFrame: Baseline, week 6
measure: Mean Change of Depression Symptom Score by PHQ-9 at Stage 2
timeFrame: week 7, week 12
measure: Mean Change of Quality of Life (QOL) by PhenX Core Tier 1 Instrument at Stage 1
timeFrame: Baseline, Week 6
measure: Mean Change of Quality of Life (QOL) by PhenX Core Tier 1 Instrument at Stage 2
timeFrame: week 7, week 12
measure: Mean Change of Overall Functioning as Measured by Treatment Effectiveness Assessment (TEA) at Stage 1
timeFrame: Baseline, week 6
measure: Mean Change of Overall Functioning as Measured by Treatment Effectiveness Assessment (TEA) at Stage 2
timeFrame: week 7, week 12
measure: Number of Participants Who Completed the Visit in Week 12
timeFrame: At week 12
measure: Participant Satisfaction Rating Measured by Study Satisfaction Survey at the End of the Study
timeFrame: At week 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA) Center for Behavioral Addiction Medicine (CBAM)
state: California
city: San Francisco
country: United States
facility: Substance Use Research Unit (SURU) at the San Francisco Dept. of Public Health
state: California
city: Minneapolis
country: United States
facility: Hennepin County Medical Center- Berman Center for Research
state: Minnesota
city: New York
country: United States
facility: New York State Psychiatric Institute (NYSPI)- Substance Use Research Center (SURC)
state: New York
city: Portland
country: United States
facility: CODA, Inc.
state: Oregon
city: Pickens
country: United States
facility: Behavioral Health Services (BHS) of Pickens County
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center - Center for Neurobehavioral Research on Addiction (CNRA)
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Madhukar Trivedi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.