NCT06233799

Brief 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 reduce MA use.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
360

participants targeted

Target at P50-P75 for phase_3

Timeline
11mo left

Started Jul 2024

Typical duration for phase_3

Geographic Reach
1 country

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress65%
Jul 2024Apr 2027

First Submitted

Initial submission to the registry

January 9, 2024

Completed
22 days until next milestone

First Posted

Study publicly available on registry

January 31, 2024

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2024

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 30, 2026

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2027

Last Updated

February 19, 2026

Status Verified

February 1, 2026

Enrollment Period

2.3 years

First QC Date

January 9, 2024

Last Update Submit

February 17, 2026

Conditions

Methamphetamine-dependenceMethamphetamine Abuse

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (5)

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

    16 weeks (12 week treatment plus followup)

  • Severity of Craving as measured by Visual Analog Scale

    16 weeks (12 week treatment plus followup)

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

    16 weeks (12 week treatment plus followup)

  • Treatment Effectiveness as measured by the Treatment Effectiveness Assessment

    16 weeks (12 week treatment plus followup)

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

    16 weeks (12 week treatment plus followup)

Study Arms (2)

XR-NTX/BUP-XL

EXPERIMENTAL

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®)

Drug: extended-release naltrexone (XR-NTX)Drug: extended release bupropion (BUP-XL) tablets (BUP-XL)

PLB/PLB

PLACEBO COMPARATOR

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.

Drug: iPLBDrug: oPLB

Interventions

extended-release naltrexone (XR-NTX)DRUG

Once per three weeks injections of extended-release naltrexone

Also known as: Vivitrol
XR-NTX/BUP-XL
iPLBDRUG

Once per three weeks injections of placebo

Also known as: Placebo injections
PLB/PLB
oPLBDRUG

Daily oral placebo tablets

Also known as: Placebo tablets
PLB/PLB
extended release bupropion (BUP-XL) tablets (BUP-XL)DRUG

Daily oral extended release bupropion tablets

Also known as: Wellbutrin
XR-NTX/BUP-XL

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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;
  • 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.

You may not qualify if:

  • 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;
  • 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;
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90038, United States

RECRUITING

University of California at San Diego

San Diego, California, 92037, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55415, United States

RECRUITING

CODA

Portland, Oregon, 97214, United States

RECRUITING

MUSC/BHS

Pickens, South Carolina, 29671, United States

RECRUITING

University of Tennessee

Memphis, Tennessee, 38119, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75247, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Interventions

vivitrolTabletsBupropion

Intervention Hierarchy (Ancestors)

Dosage FormsPharmaceutical PreparationsPropiophenonesKetonesOrganic Chemicals

Study Officials

  • Raul Mandler, MD

    NIDA/NIH

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Wong, PhD

CONTACT

301-827-6267Jennifer.Wong3@nih.gov

Jana Drgonova, PhD

CONTACT

301-827-5933jana.drgonova@nih.gov

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2024

First Posted

January 31, 2024

Study Start

July 1, 2024

Primary Completion (Estimated)

October 30, 2026

Study Completion (Estimated)

April 30, 2027

Last Updated

February 19, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Investigators don't plan to make individual participant data (IPD) available to other researchers.

Locations

US(11)