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

Tracking Information

• First Submitted Date: January 7, 2016
• First Posted Date: January 14, 2016
• Results First Submitted Date: October 25, 2021
• Results First Posted Date: June 2, 2022
• Last Update Posted Date: June 2, 2022
• Actual Study Start Date: April 18, 2016
• Actual Primary Completion Date: July 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2022)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Original Primary Outcome Measures (submitted: January 11, 2016)

PTSD Checklist to measure change in PTSD symptoms from baseline to post-treatment (4 weeks) [ Time Frame: 24-hours post-infusions; weekly for 4 weeks following last infusion ]

The PTSD Checklist (PCL) is a brief measure of the symptoms of Posttraumatic Stress Disorder. Item and total scores will be recorded and aggregated from all study participants.

Current Secondary Outcome Measures (submitted: May 6, 2022)

• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CAP-Ketamine for Antidepressant Resistant PTSD
• Official Title: CAP-Ketamine for Antidepressant Resistant PTSD
• 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.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• PTSD
• Posttraumatic Stress Disorder

Intervention

• Drug: Ketamine
  FDA approved anesthetic medication with rapid acting antidepressant effects.
• Drug: Placebo/Saline
  This is a saline placebo/non-active solution.

Study Arms

• Placebo Comparator: Placebo
  Saline dose
  Intervention: Drug: Placebo/Saline
• Experimental: Low Dose Ketamine
  Low Dose Ketamine (.20 mg/kg)
  Intervention: Drug: Ketamine
• Experimental: High Dose Ketamine
  High Dose Ketamine (.50 mg/kg)
  Intervention: Drug: Ketamine

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;:

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 6, 2022): 163
• Original Estimated Enrollment (submitted: January 11, 2016): 198
• Actual Study Completion Date: July 1, 2020
• Actual Primary Completion Date: July 1, 2020 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02655692
• Other Study ID Numbers: SPLE-003-14W
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: VA Office of Research and Development
• Original Responsible Party: Same as current
• Current Study Sponsor: VA Office of Research and Development
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: VA Office of Research and Development
• Verification Date: May 2022