CAP-Ketamine for Antidepressant Resistant PTSD

The purpose of this study is to test the safety and efficacy of repeated doses of ketamine as compared to placebo, in reducing symptoms of Posttraumatic Stress Disorder (PTSD) in an active duty military and Veteran population.

Study Overview

• Status: Completed
• Conditions: PTSD; Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Placebo/Saline

Detailed Description

In this 2-site clinical trial, intended to evaluate the safety and efficacy of repeated doses of ketamine for treatment resistant PTSD, Veterans and active duty military personnel who meet criteria for PTSD and the additional inclusion and exclusion criteria will be randomized to one of three treatment arms (placebo, low dose ketamine, high dose ketamine). Participants receive the study drug via intravenous infusion twice per week for 4-weeks.

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System, Minneapolis, MN
  • Texas
    • San Antonio, Texas, United States, 78234
      • Brooke Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• male or female Veterans or active duty military personnel between the ages of 18 and 70 years
• diagnosis of PTSD
• history of trialing one or more antidepressant medications with little to no PTSD symptom improvement
• ability to provide written informed consent

Exclusion Criteria:

• females who are currently pregnant or breastfeeding
• current high risk for suicide
• history of severe head injury

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline dose	Drug: Placebo/Saline; This is a saline placebo/non-active solution.
Experimental: Low Dose Ketamine; Low Dose Ketamine (.20 mg/kg)	Drug: Ketamine; FDA approved anesthetic medication with rapid acting antidepressant effects.
Experimental: High Dose Ketamine; High Dose Ketamine (.50 mg/kg)	Drug: Ketamine; FDA approved anesthetic medication with rapid acting antidepressant effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 1 -Day 0
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 2 - Day 1
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 3 - Day 3
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 4 - Day 7
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 5 - Day 10
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 6 - Day 14
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 7 - Day 17
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 8 - Day 21
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Session 9 - Day 24
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 1 - Day 25
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 2 - Day 28
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 3 - Day 29
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 4 - Day 35
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 5 - Day 42
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 6 - Day 49
The PTSD Checklist (PCL)	The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder (PTSD) to measure change in PTSD symptoms. The PCL-5 is a 20-item self-report measure, a total symptom severity score (range - 0-80) is obtained by summing the scores for each of the 20 items. (5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range 0-80) with higher scores indicating greater severity for PTSD	Follow-up 7 - Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 1 - Day 0
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 2 - Day 1
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 3 - Day 3
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 4 - Day 7
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 5 - Day 10
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 6 - Day 14
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 7 - Day 17
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 8 - Day 21
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Session 9 - Day 24
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 1 - Day 25
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 2 - Day 28
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 3 - Day 29
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 4 - Day 35
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 5 - Day 42
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 6 - Day 49
Montgomery-Asberg Depression Rating Scale (MADRS)	Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten-item diagnostic questionnaire to measure the severity of depression. The overall score ranges from 0 to 60 (0 to 6 - normal/symptom absent; 7 to 19 mild depression; 20 to 34 - moderate depression; >34 - severe depression)	Follow-up 7 - Day 56

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Minneapolis Veterans Affairs Medical Center; The University of Texas Health Science Center at San Antonio; Brooke Army Medical Center
• Investigators: Principal Investigator: John H. Krystal, MD, VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Publications and helpful links

General Publications

• Abdallah CG, Roache JD, Averill LA, Young-McCaughan S, Martini B, Gueorguieva R, Amoroso T, Southwick SM, Guthmiller K, Lopez-Roca AL, Lautenschlager K, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH; Consortium to Alleviate PTSD. Repeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial. Contemp Clin Trials. 2019 Jun;81:11-18. doi: 10.1016/j.cct.2019.04.009. Epub 2019 Apr 15.
• Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D'Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, Lopez-Roca AL, Lautenschlager KA, McCallin JP 3rd, Hoch MB, Timchenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology. 2022 Jul;47(8):1574-1581. doi: 10.1038/s41386-022-01266-9. Epub 2022 Jan 19. Erratum In: Neuropsychopharmacology. 2022 May 11;:

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2016
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: January 7, 2016
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: PTSD; Ketamine; Clinical Trial; Veteran; Military
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: SPLE-003-14W

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