Ketamine Treatment for PTSD and MDD in TBI

January 26, 2024 updated by: Paulo Shiroma, Minneapolis Veterans Affairs Medical Center

Examining the Efficacy and Safety of Subanesthetic Ketamine on Depression and Post-traumatic Stress Among Veterans With Mild and Moderate Traumatic Brain Injury

The goal of this clinical trial is to examine the use of sedative ketamine to treat depression and post-traumatic stress disorder (PTSD) in Veterans with mild to moderate traumatic brain injury (TBI). The main questions it aims to answer are:

  • Efficacy of ketamine to reduce symptoms of depression and/or PTSD
  • Safety of ketamine to treat depression and/or PTSD in TBI Participants will be randomly assigned to receive either ketamine or midazolam (active placebo) twice a week for 3 weeks. During participation, subjects will be interviewed, have lab tests, and complete rating scales, and questionnaires.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Medical Center
        • Contact:
        • Principal Investigator:
          • Paulo Shiroma, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Willingness/able to sign informed consent.
  • Able to read and write in English.
  • Male or female Veterans aged 18-55 years old.
  • Remote history of TBI mild-moderate that is ≥12 weeks post-injury (chronic period) that met at minimum the 2021 VA/DoD Clinical Practice Guideline for the Management and Rehabilitation of Post-Acute Mild Traumatic Brain Injury (i.e., new onset or worsening of at least one of the following clinical signs immediately following the event: loss or decreased of consciousness, period of posttraumatic amnesia, period of being dazed and confused, and neurologic deficits).
  • Lifetime history of treatment resistance to at least one adequate trial of an antidepressant as determined by the Massachusetts General Hospital Antidepressant Treatment History Questionnaire (MGH-ATRQ).
  • FDA-approved antidepressant, trazodone, atypical neuroleptic, prazosin, or clonidine with stable treatment, as determined by the study clinician, for at least 4 weeks prior to randomization. Following randomization, changes to doses may be allowable at the investigator's discretion

Exclusion Criteria:

  • Ketamine treatment within the last 6 months

    • Lifetime history of psychosis-related disorder, current episode of mania/hypomania/mixed assessed by the Mini-International Neuropsychiatric Interview (MINI 7.0 for DSM-5).
    • History of penetrating head wounds or severe traumatic brain injury (Glasgow Coma Scale <9; loss of consciousness >24hr; post-traumatic amnesia>7 days).
    • Severe substance and/or alcohol use disorder (DSM-5-TR) within six months of initial assessment; presence of illicit drugs (except cannabis) by positive urine toxicology at screening.
    • Intellectual disability or pervasive developmental disorder; dementia of any type.
    • Any disorder that, based on the Principal Investigator's judgement, would increase risk (e.g., unstable cardiac conditions) or protocol adherence (e.g., severe personality disorder).
    • For women: pregnancy (confirmed by lab test), initiation of female hormonal treatments within 3 months of screening, or inability/ unwillingness to use a medically accepted contraceptive method during the study. Women who are surgically sterile or have been post-menopausal for at least 1 year will not be excluded
    • At screening, resting blood pressure (sitting or supine) lower than 90/60 or higher than 150/90, or resting heart rate lower than 45/min or higher than 100/min.
    • Imminent risk of suicidal/homicidal ideation and/or behavior with intent and/or plan.
    • Concurrent participation in a cognitive rehabilitation program, however patient will have a TBI clinician involved in directed services.
    • Subjects on a prohibited medication: monoamine oxidase inhibitors, memantine, long acting benzodiazepines (i.e., Chlordiazepoxide, Diazepam, Flurazepam)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine
Twice a week ketamine IV 0.5 mg/kg
Drug: IV ketamine
Subjects will receive a single infusion of racemic ketamine at 0.5mg/kg for 40 minutes twice a week for 3 weeks.
Active Comparator: Midazolam
Twice a week midazolam IV 0.045 mg/kg
Drug: Midazolam
Subjects will receive a single infusion of midazolam at 0.045mg/kg for 40 minutes twice a week for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Severity of Depressive Symptoms
Time Frame: 3 weeks
Total score on the Montgomery- Åsberg Depression Rating Scale , a semi- structured 10-item scale. Range 0-60. Higher values represent worse outcomes. The total score is obtained by summing the severity score of each item.
3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Severity of Post-traumatic Stress Disorder (PTSD) Symptoms
Time Frame: 3 weeks
Total score on the PTSD Checklist for DSM-5 (PCL-5), a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The total score is obtained by summing the score of each item.
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Minneapolis Veterans Affairs Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

January 19, 2024

First Submitted That Met QC Criteria

January 26, 2024

First Posted (Estimated)

January 29, 2024

Study Record Updates

Last Update Posted (Estimated)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 26, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1770474-4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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