Ketamine for Methamphetamine Use Disorder

Phase 2

Recruiting

• Conditions: Substance Use; Substance Use Disorders; Methamphetamine Abuse
• Interventions: Drug: Ketamine Hydrochloride; Drug: Midazolam Hydrochloride

• Registration Number: NCT06496750
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

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).

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 Timeline

• Study First Submitted: 2024-07-03
• Study First Submitted QC: 2024-07-03
• Study First Posted: 2024-07-11
• Study Start: 2024-09-11
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27
• Primary Completion: 2027-02-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ketamine	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 at a constant rate over 40 minutes. IV ketamine will be administered 8 times over 6 weeks.
Midazolam	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 at a constant rate over 40 minutes. IV midazolam will be administered 8 times over 6 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adherence to treatment	6 weeks	Defined by completion of at least five out of eight IV ketamine or IV midazolam infusions.
Total abstinence	2 weeks	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).
Non-serious adverse outcomes associated with IV ketamine treatment for methamphetamine use	6 weeks	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.
Abstinence from methamphetamine use	12 weeks	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.
Differences in methamphetamine-negative urine samples from Weeks 1 to 6 and between ketamine and midazolam arms.	6 weeks	Urine samples will be collected twice a week at in-person visits.
Differences in methamphetamine-negative urine samples from Weeks 1 and 2 versus Weeks 3 and 4.	4 weeks	Urine samples will be collected twice a week at in-person visits.

Trial Locations

Locations (4)

Addiction Institute of Mount Sinai; 🇺🇸 New York, New York, United States

Interdisciplinary Substance Use and Brain Injury Facility; 🇺🇸 Albuquerque, New Mexico, United States

Prisma Health; 🇺🇸 Greenville, South Carolina, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States