Ketamine-enhanced Prolonged Exposure Therapy in PTSD

Study Overview
=================
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.

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.

Official Title
-----------------
Repeated Ketamine Treatment to Accelerate Efficacy of Prolonged Exposure in PTSD

Conditions
-----------------
PTSD

Intervention / Treatment
-----------------
* Drug: Ketamine
* Drug: Midazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine and prolonged exposure (PE)<br>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<br>* FDA approved anesthetic medication with rapid acting antidepressant effects.<br>|
| Placebo Comparator: Midazolam and prolonged exposure (PE)<br>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<br>* FDA approved sedative medication with dissociative effects.<br>|

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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Post-traumatic Stress Disorder