Ketamine-enhanced Prolonged Exposure Therapy in PTSD

Repeated Ketamine Treatment to Accelerate Efficacy of Prolonged Exposure in PTSD

The purpose of this study is to test the safety and efficacy of repeated doses of ketamine as compared to placebo to reduce symptoms of Posttraumatic Stress Disorder (PTSD) among Veteran receiving Prolonged Exposure Therapy.

Study Overview

• Status: Completed
• Conditions: PTSD
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam

Detailed Description

In this single site clinical trial, intended to evaluate the safety and efficacy of repeated doses of ketamine in conjunction with prolonged exposure (PE) therapy for PTSD. Veterans who meet criteria for PTSD and the additional inclusion and exclusion criteria will be randomized to one of two treatment arms (placebo plus PE vs ketamine plus PE). Participants receive the study drug via intravenous infusion once per week for 3-weeks.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417-2309
      • Minneapolis VA Health Care System, Minneapolis, MN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• male or female Veterans between the ages of 18 and 75 years
• diagnosis of PTSD
• ability to provide written informed consent

Exclusion Criteria:

• females who are currently pregnant or breastfeeding
• current high risk for suicide
• history of moderate/severe head injury
• history of psychosis
• current episode of mania/hypomania
• severe substance and/or alcohol use disorder in the last 6 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine and prolonged exposure (PE); Single IV ketamine 0.5 mg/kg 24-72 hrs prior to PE session at week 1,2, and 3 followed by 7 additional PE sessions.	Drug: Ketamine; FDA approved anesthetic medication with rapid acting antidepressant effects.
Placebo Comparator: Midazolam and prolonged exposure (PE); Single IV midazolam 0.045 mg/kg 24-72 hrs prior to PE session at week 1,2, and 3 followed by 7 additional PE sessions.	Drug: Midazolam; FDA approved sedative medication with dissociative effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)	The CAPS-5 is the gold standard in PTSD assessment consisting of a a 30-item structured interview. The CAPS-5 will be recorded and aggregated from all study participants. Range from 0 to 80 with higher score denoting more severe PTSD symptoms.	CAPS-5 to measure change in PTSD symptoms from baseline to post-treatment (10 weeks)

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Paulo R Shiroma, MD, Minneapolis VA Health Care System, Minneapolis, MN

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): October 7, 2025

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 23, 2020

Study Record Updates

• Last Update Posted (Estimated): October 10, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Post-traumatic Stress Disorder
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; 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: MHBP-006-19F

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
• product manufactured in and exported from the U.S.: No