CAP-Ketamine for Antidepressant Resistant PTSD

• ClinicalTrials.gov Identifier: NCT02655692
• Recruitment Status: Completed
• First Posted: January 14, 2016
• Results First Posted: June 2, 2022
• Last Update Posted: June 2, 2022
• Sponsor: VA Office of Research and Development
• Collaborators: The University of Texas Health Science Center at San Antonio; Brooke Army Medical Center; Minneapolis Veterans Affairs Medical Center
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
PTSD; Posttraumatic Stress Disorder	Drug: Ketamine; Drug: Placebo/Saline	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 163 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: CAP-Ketamine for Antidepressant Resistant PTSD
• Actual Study Start Date: April 18, 2016
• Actual Primary Completion Date: July 1, 2020
• Actual Study Completion Date: July 1, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. PTSD Checklist (PCL) [ Time Frame: Session 1 -Day 0 ]
   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
2. The PTSD Checklist (PCL) [ Time Frame: Session 2 - Day 1 ]
   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
3. The PTSD Checklist (PCL) [ Time Frame: Session 3 - Day 3 ]
   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
4. The PTSD Checklist (PCL) [ Time Frame: Session 4 - Day 7 ]
   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
5. The PTSD Checklist (PCL) [ Time Frame: Session 5 - Day 10 ]
   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
6. The PTSD Checklist (PCL) [ Time Frame: Session 6 - Day 14 ]
   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
7. The PTSD Checklist (PCL) [ Time Frame: Session 7 - Day 17 ]
   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
8. The PTSD Checklist (PCL) [ Time Frame: Session 8 - Day 21 ]
   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
9. The PTSD Checklist (PCL) [ Time Frame: Session 9 - Day 24 ]
   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
10. The PTSD Checklist (PCL) [ Time Frame: Follow-up 1 - Day 25 ]
    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
11. The PTSD Checklist (PCL) [ Time Frame: Follow-up 2 - Day 28 ]
    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
12. The PTSD Checklist (PCL) [ Time Frame: Follow-up 3 - Day 29 ]
    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
13. The PTSD Checklist (PCL) [ Time Frame: Follow-up 4 - Day 35 ]
    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
14. The PTSD Checklist (PCL) [ Time Frame: Follow-up 5 - Day 42 ]
    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
15. The PTSD Checklist (PCL) [ Time Frame: Follow-up 6 - Day 49 ]
    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
16. The PTSD Checklist (PCL) [ Time Frame: Follow-up 7 - Day 56 ]
    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

Secondary Outcome Measures :

1. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 1 - Day 0 ]
   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)
2. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 2 - Day 1 ]
   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)
3. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 3 - Day 3 ]
   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)
4. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 4 - Day 7 ]
   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)
5. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 5 - Day 10 ]
   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)
6. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 6 - Day 14 ]
   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)
7. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 7 - Day 17 ]
   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)
8. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 8 - Day 21 ]
   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)
9. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Session 9 - Day 24 ]
   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)
10. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 1 - Day 25 ]
    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)
11. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 2 - Day 28 ]
    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)
12. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 3 - Day 29 ]
    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)
13. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 4 - Day 35 ]
    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)
14. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 5 - Day 42 ]
    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)
15. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 6 - Day 49 ]
    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)
16. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Follow-up 7 - Day 56 ]
    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)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Connecticut

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, United States, 06516

United States, Minnesota

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States, 55417

United States, Texas

Brooke Army Medical Center

San Antonio, Texas, United States, 78234

Sponsors and Collaborators

VA Office of Research and Development

The University of Texas Health Science Center at San Antonio

Brooke Army Medical Center

Minneapolis Veterans Affairs Medical Center

Investigators

• Principal Investigator: John H. Krystal, MD; VA Connecticut Healthcare System West Haven Campus, West Haven, CT

  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:

Study Protocol  [PDF] March 31, 2021

Statistical Analysis Plan  [PDF] March 31, 2021

More Information

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;:

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02655692
• Other Study ID Numbers: SPLE-003-14W
• First Posted: January 14, 2016
• Results First Posted: June 2, 2022
• Last Update Posted: June 2, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by VA Office of Research and Development:

PTSD; Ketamine; Veteran; Military; Clinical Trial

Additional relevant MeSH terms:

Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action