Study 47 – Ketamine for Methamphetamine Use Disorder (KMD); CTN-0132

Principal Investigator: Madhukar H. Trivedi, M.D.

Co-Investigators: Manish K. Jha, MBBS; Sidarth Wakhlu, M.D., Thomas Carmody, Ph.D.

Release Date: TBA

Objective: The primary objective of this study will be to assess preliminary efficacy, safety, and feasibility of a course of intravenous (IV) ketamine (compared with IV midazolam) as a treatment for methamphetamine use disorder.

Significance/Impact: 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. Over the past 20 years, robust evidence has been gathered on ketamine use for treatment resistant major depressive disorder (MDD), as well as promising evidence for a range of psychiatric disorders and several substance use disorders. In addition, the s-enantiomer of ketamine (esketamine) is now an FDA approved treatment for treatment-resistant MDD in adults and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior. Currently, however, there is little research on ketamine for MUD, yet the potential for ketamine to alter neurobiology of MUD and/or to mitigate early withdrawal symptoms from regular methamphetamine use merits study. 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 IV ketamine in MUD.

Study Design/Methodology: This study is a 12-week randomized, double-blind, controlled trial comparing IV ketamine against IV midazolam, delivered over six weeks (acute-phase of twice-weekly infusions during Weeks 1, 2,  and 3, and one infusion during Week 4, followed by continuation-phase of one infusion during Week 6; total of eight (8) infusions over the six-week period) in 120 adults with moderate to severe methamphetamine use disorder (MUD) (without co-existing opioid use disorder of moderate or severe severity). Participants will be involved in the study for approximately 16 weeks, including a screening period of up to one month (i.e., 30 days), six weeks in the active medication phase, and six weeks of follow-up visits, ending with Week 12.