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

Minneapolis Veterans Affairs Medical Center1 site in 1 country40 target enrollmentMarch 2024

ConditionsPTSD, Post Traumatic Stress Disorder Major Depressive Disorder Traumatic Brain Injury

InterventionsIV ketamine Midazolam

DrugsIV ketamine Midazolam

Overview

Phase: Phase 2
Intervention: IV ketamine
Conditions: PTSD, Post Traumatic Stress Disorder
Sponsor: Minneapolis Veterans Affairs Medical Center
Enrollment: 40
Locations: 1
Primary Endpoint: Change in Severity of Depressive Symptoms
Status: Not yet recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

March 2024

End Date

March 2027

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Minneapolis Veterans Affairs Medical Center

Responsible Party

Principal Investigator

Paulo Shiroma

Psychiatrist

Minneapolis Veterans Affairs Medical Center

Eligibility Criteria

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.

Arms & Interventions

Ketamine

Twice a week ketamine IV 0.5 mg/kg

Intervention: IV ketamine

Midazolam

Twice a week midazolam IV 0.045 mg/kg

Intervention: Midazolam

Outcomes

Primary Outcomes

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.