Quetiapine to Reduce Post Concussive Syndrome After Mild Traumatic Brain Injury (mTBI)

NCT06333990 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 20220796HU
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 2

Brief Summary

A two site, 2-arm, Phase III randomized pragmatic clinical trial evaluating the effectiveness of quetiapine monotherapy in comparison to Treatment As Usual (TAU) medication management for symptoms experienced by veterans receiving rehabilitation therapy for mild traumatic brain injury (mTBI) and comorbid symptoms of posttraumatic stress disorder (PTSD).

Conditions

Mild Traumatic Brain Injury

Keywords

Post Concussive Syndrome (PCS); Posttraumatic Stress Disorder (PTSD); Polypharmacy; Quetiapine; Veterans

Outcome Measures

Primary Outcomes (3)

• Neurobehavioral Symptom Inventory

  A 22- item, self-report measure of symptoms of postconcussive symptoms severity for the preceding 2 week period. Items are scored on a 5-point scale, and a total score is obtained by summing the 22 symptom items, with higher scores indicate greater symptom severity. The total scores range from 0 - 88.

  2 weeks

• World Health Organization Disability Assessment Scale

  A 12-item, self-report measure of functional disability for the preceding 30 days. Items are scored on a 5-point scale, and a total score is obtained by summing the 12 activities, with higher scores indicate greater disability. The total scores range from 0 - 48.

  30 days

• World Health Organization Quality of Life BREF

  A 26- item, self-report measure to assess functioning and quality of life for the preceding 2 week period. It is a measure of conceptual domains of quality of life: material and physical well-being, relationships with other people, social, community and civic activities, personal development and fulfillment, independence, and recreation.

  2 weeks

Study Arms (2)

Quetiapine

EXPERIMENTAL

Quetiapine will be cross-tapered up to a maximum dose of 200 mg (as tolerated) as other standard of care medications are discontinued.

Drug: Quetiapine Fumarate

Treatment As Usual (TAU)

ACTIVE COMPARATOR

Participants in the TAU group will have doses adjusted over the same period as indicated by usual care criteria.

Drug: TAU

Interventions

Quetiapine Fumarate DRUG

Quetiapine is an atypical antipsychotic approved by the FDA for the treatment of schizophrenia, bipolar disorder, and as an adjunct to treat major depression. It has a broad spectrum of actions at dopaminergic (D1, D2, D3 and D4), serotonergic (5-HT2A, 5-HT2C and 5-HT7), adrenergic (α1), histaminic (H1) and muscarinic (mACh), and partial agonist at 5-HT1A receptors.

Also known as: Seroquel

Quetiapine

TAU DRUG

Standard of care psychotropic medications for treatment of patients with mTBI.

Also known as: Treatment As Usual

Treatment As Usual (TAU)

Eligibility Criteria

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

You may qualify if:

• Male or female veterans seeking treatment for mTBI, aged 18-65 years
• Meet mTBI diagnosis and have PCS symptoms reported on the Neurobehavioral Symptom Inventory (NSI). Six months or more must elapse between the injury and Screening. mTBI diagnosis will be determined using the provisional diagnostic convention recommended by the VA/DoD requiring loss of consciousness, or a period of altered consciousness, or posttraumatic amnesia;
• Be stable (i.e., no dose changes for \> 1 month) on at least three CNS active psychotropic medications prescribed for symptom relief or psychiatric treatment.
• Have posttraumatic symptoms measured by PTSD Checklist for DSM-5 (PCL-5) score ≥25.

You may not qualify if:

• Moderate or severe TBI, or major neurocognitive disorder (dementia).
• Meet DSM-5 criteria for schizophrenia, bipolar disorder, schizoaffective disorder, or requiring inpatient hospitalization currently or within past 6 months.
• Currently taking any antipsychotics or prohibited medication within the past month .
• Known intolerance to quetiapine or a history of clinically unstable heart, lung, liver, renal, hematological, or endocrinological condition, diabetes mellitus, severe sleep apnea and/or seizure disorder.
• Substance use disorder severe enough to require medication treatment or medical detoxification or inpatient hospitalization within 6 months of screening.
• Reporting suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months prior to screening or at screening or baseline visit (i.e. active suicidal thought with method and intent but without specific plan, or active suicidal thought with method, intent, and plan); or homicidal ideation with intent or plan to harm others within 90 days or suicide attempt; or suicidal behavior within 6 months prior to screening.
• (Note: Study psychiatrist will be immediately notified when SI or HI intent is positive)
• Current or known history of cardiac arrhythmia or QTc interval ≥ 470 milliseconds.
• Pregnant or lactating women and those of child-bearing potential not using a reliable method of contraception will be excluded from participating in the study.

Sponsors & Collaborators

• Foundation for Advancing Veterans' Health Research: lead
• The University of Texas Health Science Center at San Antonio: collaborator
• Biomedical Research Institute of New Mexico: collaborator

Study Sites (2)

New Mexico VA Healthcare System

Albuquerque, New Mexico, 87108, United States

RECRUITING

South Texas Veterans Healthcare System

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Brain Concussion; Post-Concussion Syndrome; Stress Disorders, Post-Traumatic

Interventions

Quetiapine Fumarate; Therapeutics

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Muhammad R Baig, MD

CONTACT

210-617-5300; muhammad.baig@va.gov

Lizette Aviles, BS

CONTACT

361-277-5486; lizette.aviles@va.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 27, 2024
• Study Start: July 9, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Anticipated June 2028

Locations

US (2)