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

A Randomized Clinical Trial of Quetiapine to Reduce Post Concussive Syndrome Polypharmacy

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Traumatic Brain Injury
• Intervention / Treatment: Drug: Quetiapine Fumarate; Drug: TAU

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Muhammad R Baig, MD; Phone Number: 18244 210-617-5300; Email: muhammad.baig@va.gov
• Study Contact Backup: Name: Lizette Aviles, BS; Phone Number: 361-277-5486; Email: lizette.aviles@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female veterans seeking treatment for mTBI, aged 18-65 years
2. 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;
3. 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.
4. Have posttraumatic symptoms measured by PTSD Checklist for DSM-5 (PCL-5) score ≥25.

Exclusion Criteria:

1. Moderate or severe TBI, or major neurocognitive disorder (dementia).
2. Meet DSM-5 criteria for schizophrenia, bipolar disorder, schizoaffective disorder, or requiring inpatient hospitalization currently or within past 6 months.
3. Currently taking any antipsychotics or prohibited medication within the past month .
4. 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.
5. Substance use disorder severe enough to require medication treatment or medical detoxification or inpatient hospitalization within 6 months of screening.

6. 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)

7. Current or known history of cardiac arrhythmia or QTc interval ≥ 470 milliseconds.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quetiapine; 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; 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.; Other Names: Seroquel
Active Comparator: Treatment As Usual (TAU); Participants in the TAU group will have doses adjusted over the same period as indicated by usual care criteria.	Drug: TAU; Standard of care psychotropic medications for treatment of patients with mTBI.; Other Names: Treatment As Usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Veterans; Polypharmacy; Quetiapine; Posttraumatic Stress Disorder (PTSD); Post Concussive Syndrome (PCS)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Injuries, Traumatic; Post-Concussion Syndrome; Brain Concussion; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: 20220796HU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified IPD will be shared with the research community through Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System.
• IPD Sharing Time Frame: Anticipated June 2028
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No