Ketamine Treatment for PTSD and MDD in TBI

NCT06228391 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 1770474-4
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

Veteran; Ketamine; PTSD; Depression; TBI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Severity of Post-traumatic Stress Disorder (PTSD) Symptoms

  3 weeks

Study Arms (2)

Ketamine

EXPERIMENTAL

Twice a week ketamine IV 0.5 mg/kg

Drug: IV ketamine

Midazolam

ACTIVE COMPARATOR

Twice a week midazolam IV 0.045 mg/kg

Drug: Midazolam

Interventions

IV ketamine DRUG

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

Ketamine

Midazolam DRUG

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

Midazolam

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Minneapolis Veterans Affairs Medical Center: lead

Study Sites (1)

Minneapolis VA Medical Center

Minneapolis, Minnesota, 55417, United States

Location

MeSH Terms

Conditions

Combat Disorders; Depressive Disorder, Major; Brain Injuries, Traumatic; Stress Disorders, Post-Traumatic; Depression

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Paulo Shiroma, MD

CONTACT

612-467-2264; paulo.shiroma@va.gov

Seth Dsiner, PhD

CONTACT

612-629-7349; seth.disner@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: January 29, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 29, 2024

Record last verified: 2024-01

Locations

US (1)