Ketamine Treatment for PTSD and MDD in TBI

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06228391
• Other study ID #: 1770474-4
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2024
• Est. completion date: March 2027

Study information

• Verified date: January 2024
• Source: Minneapolis Veterans Affairs Medical Center
• Contact: Paulo Shiroma, MD
• Phone: 612-467-2264
• Email: paulo.shiroma[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: March 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• PTSD, Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic
• Traumatic Brain Injury

Intervention

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.
• Midazolam
Subjects will receive a single infusion of midazolam at 0.045mg/kg for 40 minutes twice a week for 3 weeks.

Locations

Country	Name	City	State
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Minneapolis Veterans Affairs Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Severity of Depressive Symptoms	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	Change in Severity of Post-traumatic Stress Disorder (PTSD) Symptoms	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