Ketamine Treatment for PTSD and MDD in TBI

NCT ID: NCT06228391

Last Updated: 2024-01-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2027-03-31

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.

Conditions

PTSD, Post Traumatic Stress Disorder; Major Depressive Disorder; Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

Twice a week ketamine IV 0.5 mg/kg

Group Type: EXPERIMENTAL

IV ketamine

Intervention Type: DRUG

Subjects will receive a single infusion of racemic ketamine at 0.5mg/kg for 40 minutes twice a week for 3 weeks.

Midazolam

Twice a week midazolam IV 0.045 mg/kg

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

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

Interventions

IV ketamine

Subjects will receive a single infusion of racemic ketamine at 0.5mg/kg for 40 minutes twice a week for 3 weeks.

Intervention Type: DRUG

Midazolam

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

Intervention Type: DRUG

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.
• Subjects on a prohibited medication: monoamine oxidase inhibitors, memantine, long acting benzodiazepines (i.e., Chlordiazepoxide, Diazepam, Flurazepam)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Minneapolis Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Paulo Shiroma

Psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Minneapolis VA Medical Center

Minneapolis, Minnesota, United States

Countries

United States

Central Contacts

Paulo Shiroma, MD

Role: CONTACT

paulo.shiroma@va.gov

612-467-2264

Seth Dsiner, PhD

Role: CONTACT

seth.disner@va.gov

612-629-7349

Facility Contacts

Paulo Shiroma, MD

Role: primary

paulo.shiroma@va.gov

612-467-2264

Other Identifiers

1770474-4

Identifier Type: -

Identifier Source: org_study_id