Ketamine-enhanced Prolonged Exposure Therapy in PTSD

NCT04560660 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MHBP-006-19F
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PTSD

Keywords

Post-traumatic Stress Disorder

Outcome Measures

Primary Outcomes (5)

• 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.

  Baseline

• 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.

  Week 4

• 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.

  Week 10

• 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.

  Week 14

• 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.

  Week 22

Study Arms (2)

Ketamine and prolonged exposure (PE)

EXPERIMENTAL

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

Midazolam and prolonged exposure (PE)

PLACEBO COMPARATOR

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

Interventions

Ketamine DRUG

FDA approved anesthetic medication with rapid acting antidepressant effects.

Ketamine and prolonged exposure (PE)

Midazolam DRUG

FDA approved sedative medication with dissociative effects.

Midazolam and prolonged exposure (PE)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The study did not achieve its planned sample size due to delays in hiring research therapists, which reduced our dedicated research capacity. To maintain study operations, the investigators relied on clinical therapists; however, their availability was constrained by ongoing clinical responsibilities. This competition with clinical demands further limited the number of participants who could be enrolled during the recruitment period.

Results Point of Contact

• Title: Paulo R. Shiroma, MD
• Organization: Minneapolis VA Healthcare System

paulo.shiroma@va.gov

612-467-2264

Study Officials

• Paulo R Shiroma, MD

  Minneapolis VA Health Care System, Minneapolis, MN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigators will use a sequentially numbered, opaque, sealed envelopes, pharmacy-controlled allocations, and coded identical containers for adequate concealment allocation. Administration of study drugs and infusion monitoring will be conducted by research nurse keeping blinding from investigators and independent outcome assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Subjects will be randomly assigned to one of two parallel treatment conditions: 1) adjunctive ketamine infusions to prolonged exposure therapy or 2) adjunctive midazolam (active placebo) infusions to prolonged exposure therapy.

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 23, 2020
• Study Start: March 9, 2021
• Primary Completion: July 1, 2025
• Study Completion: October 7, 2025
• Last Updated: July 15, 2026
• Results First Posted: July 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)