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Methamphetamine-dependencePhase 3NCT06233799

Trial of Naltrexone/Bupropion for the Treatment of Methamphetamine Use Disorder

A Phase 3 study testing extended-release naltrexone (XR-NTX), extended release bupropion (BUP-XL) tablets (BUP-XL) and iPLB in people with Methamphetamine-dependence and Methamphetamine Abuse, run by National Institute on Drug Abuse (NIDA) at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
extended-release naltrexone (XR-NTX), extended release bupropion (BUP-XL) tablets (BUP-XL) and iPLB
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
360 participants
Where
11 sitesUnited States
Study dates
1 Jul 2024to 30 Apr 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Is 18 to 65 years of age;
  • Meets DSM-5 criteria for moderate or severe MUD (4 or more criteria);
  • Is interested in reducing or stopping MA use;
  • Is able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study;
  • Self-reports MA use on 18 or more days in the 30-day period prior to consent using the Timeline Followback (TLFB);
  • Provides at least 2 urine samples positive for MA out of up to 3 tests, which will occur at least 2 days apart within a 10-day period;
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  • If assigned as female at birth and/or currently has a uterus, is not pregnant, agrees to use acceptable birth control methods, and have periodic urine pregnancy testing done during participation in the study unless documentation of hysterectomy provided;
  • Is not physically dependent on opioids and meets subjective and objective measures of being opioid-free prior to naltrexone injection per study medical clinician's determination, including, if clinically required, a negative naloxone challenge;
  • Is willing to comply with all study procedures and medication instructions;
  • Agrees to use a smartphone app (downloaded for free to own device or on a study provided smartphone device) to take daily videos of medication dosing.

Who cannot join

  • Has an acute medical or psychiatric disorder that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
  • Has suicidal or homicidal ideation that requires immediate attention;
  • Has a history of epilepsy, seizure disorder, or head trauma with neurological sequelae (e.g., loss of consciousness that required hospitalization); current anorexia nervosa or bulimia; or any other conditions that increase seizure risk in the opinion of the study medical clinician;
  • Has evidence of second or third degree heart block, atrial fibrillation, atrial flutter, prolongation of the QTc, or any other finding on the screening ECG that, in the opinion of the study medical clinician, would preclude safe participation in the study;
  • Has Stage 2 hypertension as determined by the study medical clinician (e.g., greater than or equal to 160/100 in 2 out of 3 readings during screening);
  • Has any elevated bilirubin test value per laboratory criteria OR any other liver function test (LFT) value > 5 times the upper limit of normal per laboratory criteria;
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  • Has a platelet count <100 x 10exp3/microliter;
  • Has a body habitus that precludes gluteal intramuscular injection of XR-NTX in accordance with the administration equipment (needle) and procedures;
  • Has a known allergy or sensitivity to bupropion, naloxone, naltrexone, PLG (polyactideco-glycolide), carboxymethylcellulose or any other component of the XR-NTX diluents;
  • Has been in a prior study of pharmacological or behavioral treatment for MUD within 6 months of study consent;
  • Has taken an investigational drug in another study within 30 days of study consent;
  • Has been prescribed and taken naltrexone or bupropion within 30 days of study consent;
  • Is concurrently enrolled in formal behavioral or pharmacological Substance Use Disorder (SUD) treatment services;
  • Is receiving ongoing treatment with tricyclic antidepressants, xanthines (i.e., theophylline and aminophylline), systemic corticosteroids, nelfinavir, efavirenz, chlorpromazine, MAOIs, central nervous system stimulants (e.g., Adderall, Ritalin, etc.), or any medication that, in the judgment of the study medical clinician, could interact adversely with study medications;
  • Has a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use which would preclude safe participation in the study as determined by the study medical clinician;
  • Requires treatment with opioid-containing medications (e.g., opioid analgesics) during the study period;
  • Has a surgery planned or scheduled during the study period;
  • Is currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that could prevent participation in the study or in any study activities;
  • If assigned as female at birth and/or currently has a uterus, is currently pregnant, breastfeeding, or planning on conception.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Virginia

    Charlottesville, Virginia, 22903

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75247

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • University of California Los Angeles

    Los Angeles, California, 90038

  • University of Tennessee

    Memphis, Tennessee, 38119

  • University of Minnesota

    Minneapolis, Minnesota, 55415

  • MUSC/BHS

    Pickens, South Carolina, 29671

  • CODA

    Portland, Oregon, 97214

  • University of California at San Diego

    San Diego, California, 92037

Other trials in United States

About this study

Official title: Randomized, Placebo-Controlled, Multi-Site Trial of Extended-Release Naltrexone Injection/Bupropion XL Tablets in the Treatment of Methamphetamine Use Disorder

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.

Read the detailed description

This is a double-blind, placebo-controlled, randomized clinical trial in which 360 individuals with moderate or severe MUD will be randomly assigned at a 1:1 ratio to receive either 1) extended release naltrexone (XR-NTX; as Vivitrol®) plus once daily oral extended release bupropion (BUP-XL) tablets (the XR-NTX/BUP-XL group) or 2) both the matching injection placebo (iPLB) and once daily oral placebo (oPLB) tablets (the iPLB/oPLB group). The study intervention consists of a 12-week treatment phase. It is hypothesized that the XR-NTX/BUP-XL arm will be associated with a greater number of "responders," defined as participants who provide at least 3 MA-negative urine drug screens (UDS) out of 4 samples obtained during the evaluation period (i.e., Weeks 11-12) of the 12-week long treatment phase, relative to the iPLB/oPLB arm. Secondary objectives include evaluating the effect of the extended release naltrexone plus bupropion XL (XR-NTX/BUP-XL) arm compared to the iPLB/oPLB arm on safety, other substance use outcomes, depression scores, quality of life, overall functioning, clinic attendance, and medication adherence.

Being tested
extended-release naltrexone (XR-NTX), extended release bupropion (BUP-XL) tablets (BUP-XL), iPLB, oPLB

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • extended-release naltrexone (XR-NTX)Drug

    Also called Vivitrol

    Once per three weeks injections of extended-release naltrexone

  • extended release bupropion (BUP-XL) tablets (BUP-XL)Drug

    Also called Wellbutrin

    Daily oral extended release bupropion tablets

  • iPLBDrug

    Also called Placebo injections

    Once per three weeks injections of placebo

  • oPLBDrug

    Also called Placebo tablets

    Daily oral placebo tablets

Study groups in NCT06233799
Study groupRoleWhat they receive
XR-NTX/BUP-XLExperimentalParticipants 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®)
Receives: Drug: extended-release naltrexone (XR-NTX); Drug: extended release bupropion (BUP-XL) tablets (BUP-XL)
PLB/PLBPlacebo comparatorParticipants randomized to the PLB arm will receive once-daily placebo tablets and once every three weeks (Weeks 1, 4, 7, and 10) placebo injections.
Receives: Drug: iPLB; Drug: oPLB

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with at least 75% methamphetamine-negative urine drug screen tests during the evaluation period (i. e., Weeks 11-12)

    Participants will be administered four urine drug screen tests (two tests/week) during the evaluation period. (i.e., Weeks 11-12).

    Measured: 2 weeks (i. e., Weeks 11-12)

Secondary outcomes (5)

  1. safety measured as frequency and severity of adverse events (AEs)

    adverse events (AEs), clinical lab tests, suicidality

    Measured: 16 weeks (12 week treatment plus followup)

  2. Severity of Craving as measured by Visual Analog Scale

    Craving score as assessed by Visual Analog Scale that ranges from 0 (no craving) to 100 (most intense craving possible). The Visual Analog Scale will be completed at each screening visit, twice weekly throughout the treatment phase, and at the Week 14 and 16 follow-up visits.

    Measured: 16 weeks (12 week treatment plus followup)

  3. Severity of Depression as assessed by the Patient Health Questionnaire-9

    Diagnostic criteria for major depression, severity and frequency of depressive symptoms, presence of suicidal ideation, and functional impairment related to depression will be assessed by the Patient Health Questionnaire-9 (Kroenke et al., 2001)

    Measured: 16 weeks (12 week treatment plus followup)

  4. Treatment Effectiveness as measured by the Treatment Effectiveness Assessment

    The Treatment Effectiveness Assessment (TEA; Ling et al., 2012) is a 4-item self-administered assessment to document changes in four life domains: substance use, personal responsibilities, health, and community. The TEA will be collected at screening, mid-treatment (Week 6 visit 2), end-of-treatment (Week 12 visit 2), and follow-up (Weeks 14 and 16).

    Measured: 16 weeks (12 week treatment plus followup)

  5. Quality of Life as measured by PROMIS® Profile 29 for adults

    The instrument includes 29 self-administered questions from the PROMIS® Profile 29 for adults. The quality of life questions include physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain intensity over the past 30 days. Each question, except for the pain intensity question, is measured on a 5-point scale. Quality of Life will be assessed at screening, mid-treatment (Week 6 visit 2), end-of-treatment (Week 12 visit 2), and follow-up (Weeks 14 and 16).

    Measured: 16 weeks (12 week treatment plus followup)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2024
  2. Study start1 Jul 2024
  3. Primary completion30 Oct 2026 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
360 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06233799
Sponsor's protocol ID
NIDA/VA CS #1036
Status last verified
Feb 2026
First submitted
9 Jan 2024
Last updated
13 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Investigators don't plan to make individual participant data (IPD) available to other researchers.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing extended-release naltrexone (XR-NTX), extended release bupropion (BUP-XL) tablets (BUP-XL) and iPLB in people with Methamphetamine-dependence and Methamphetamine Abuse, run by National Institute on Drug Abuse (NIDA) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with at least 75% methamphetamine-negative urine drug screen tests during the evaluation period (i. e., Weeks 11-12) (time frame: 2 weeks (i. e., Weeks 11-12)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06233799.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.

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