Ketamine for Methamphetamine Use Disorder (KMD)

NIDA CTN-0132 Randomized, Double-Blind, Active Placebo-Controlled Trial of Ketamine for Methamphetamine Use Disorder (KMD)

This study aims to determine whether treatment response with IV ketamine is superior to treatment response with IV midazolam in adults with moderate to severe MUD.

The study design is a 12-week randomized, double-blind, controlled trial comparing intravenous (IV) ketamine against IV midazolam, delivered over six weeks in 120 adults with moderate to severe methamphetamine use disorder (MUD).

Study Overview

• Status: Recruiting
• Conditions: Substance Use; Substance Use Disorders; Methamphetamine Abuse
• Intervention / Treatment: Drug: Ketamine Hydrochloride; Drug: Midazolam Hydrochloride

Detailed Description

Effective management for methamphetamine use disorder (MUD) remains elusive, despite widespread misuse of this stimulant. Psychological interventions have demonstrated modest benefits, and relapse rates are high. There are currently no Food and Drug Administration (FDA)-approved pharmacotherapies for MUD. This study explores the efficacy, safety, and feasibility for intravenous (IV) ketamine as a treatment for MUD and will help to determine the effect size for a larger, multi-site trial of intravenous (IV) ketamine in MUD.

Participants will receive either IV ketamine (0.50mg/kg) or IV midazolam (0.02mg/kg) over 45 minutes per infusion for a total of eight (8) infusions over six (6) weeks. Medical management sessions with a study clinician will be provided to all participants once weekly (from Weeks 1 through 6).

The use of IV ketamine in this trial is consistent in dose (0.5 mg/kg) and duration of infusion (45-minute-long) to other studies of ketamine for psychiatric disorders (such as major depressive disorder and post-traumatic stress disorder, both of which are often comorbid in individuals with MUD) and substance use disorder. However, IV ketamine has not been directly evaluated as mono-pharmacotherapy in those with MUD yet.

Additionally, participants will be asked to participate in cognitive behavioral therapy (CBT) sessions once weekly (from Weeks 1 through 12) on a non-infusion day.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Angela Casey-Willingham; Phone Number: 214-648-4689; Email: Angela.Casey-Willingham@UTSouthwestern.edu

Study Locations

• United States
  • California
    • San Leandro, California, United States, 94578
      • Recruiting
      • Alameda Health System
      • Principal Investigator: Erik Anderson, MD
      • Contact: Stephanie Gallardo, BA; Phone Number: 510-495-4643; Email: stgallardo@alamedahealthsystem.org
      • Contact: Bridge Clinic; Phone Number: 510-545-2765
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Completed
      • Interdisciplinary Substance Use and Brain Injury Facility
  • New York
    • New York, New York, United States, 10029
      • Terminated
      • Addiction Institute of Mount Sinai
  • South Carolina
    • Greenville, South Carolina, United States, 29617
      • Recruiting
      • Prisma Health
      • Principal Investigator: Alain Litwin, MD
      • Contact: Sarah; Phone Number: 864-960-3183; Email: sarah.feingold@prismahealth.org
      • Contact: Anthony; Phone Number: 864-735-8682; Email: Anthony.Faso@prismahealth.org
  • Texas
    • Dallas, Texas, United States, 75247
      • Active, not recruiting
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

Study participants must:

1. Be 18 to 65 years old
2. Be able to sufficiently understand, speak, and read English
3. Be interested in reducing or stopping methamphetamine use
4. Meet criteria for methamphetamine use disorder
5. Use acceptable methods of contraception during participation in the study

Exclusion criteria

Study participants must not:

1. Have been in a research study of pharmacological or behavioral treatment for addiction within 6 months prior to written informed consent
2. Be currently in jail, prison, or inpatient overnight facility as required by court of law
3. Have upcoming surgery planned or scheduled
4. Be currently pregnant, breastfeeding, or planning on conception, if biologically female

Additional inclusion and exclusion criteria will be assessed by the study investigators at the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Participants will receive IV ketamine (0.50mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump at a constant rate over 40 minutes. IV ketamine will be administered 8 times over 6 weeks.	Drug: Ketamine Hydrochloride; Participants will receive IV ketamine (0.50mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump over 45 minutes. Duration of each infusion may be extended by the Study Clinician supervising study medication infusion if slower infusion rate is better tolerated.; Other Names: Ketelar
Active Comparator: Midazolam; Participants will receive IV midazolam (0.02mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump at a constant rate over 40 minutes. IV midazolam will be administered 8 times over 6 weeks.	Drug: Midazolam Hydrochloride; Participants will receive IV midazolam (0.02mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump over 45 minutes. Duration of each infusion may be extended by the Study Clinician supervising study medication infusion if slower infusion rate is better tolerated.; Other Names: Versed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Response	Defined as having at least three methamphetamine-negative urine samples out of four samples obtained during Weeks 3 and 4.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-serious adverse outcomes associated with IV ketamine treatment for methamphetamine use	Defined by non-serious adverse events (associated with the IV ketamine treatment) reported during the study intervention phase (weeks 1 to 6). Participants will be assessed for adverse events at each study visit.	6 weeks
Adherence to treatment	Defined by completion of at least five out of eight IV ketamine or IV midazolam infusions.	6 weeks
Total abstinence	Defined as four out of four methamphetamine-negative urine samples obtained during Weeks 3 and 4 (since missing urine drug screens will be counted as positive).	2 weeks
Abstinence from methamphetamine use	Defined by the self-reported days of methamphetamine use as reported on the Timeline Followback (TLFB) from Week 1 to Week 4, Week 5 to Week 6, and Week 7 to Week 12.	12 weeks
Differences in methamphetamine-negative urine samples from Weeks 1 to 6 and between ketamine and midazolam arms.	Urine samples will be collected twice a week at in-person visits.	6 weeks
Differences in methamphetamine-negative urine samples from Weeks 1 and 2 versus Weeks 3 and 4.	Urine samples will be collected twice a week at in-person visits.	4 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Madhukar Trivedi, MD, Professor (Tenured)

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Estimated): August 18, 2026
• Study Completion (Estimated): October 15, 2026

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Benzazepines; Benzodiazepines; Midazolam; Ketamine
• Other Study ID Numbers: STU-2023-1086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No