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

Foundation for Advancing Veterans' Health Research

Status and phase: Enrolling; Phase 3

Conditions: Mild Traumatic Brain Injury

Treatments: Drug: TAU; Drug: Quetiapine Fumarate

Study type: Interventional

Funder types: Other

Identifiers

NCT06333990

20220796HU

Details and patient eligibility

About

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).

Enrollment: 146 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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146 participants in 2 patient groups

Quetiapine

Experimental group

Description:

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

Treatment:

Drug: Quetiapine Fumarate

Treatment As Usual (TAU)

Active Comparator group

Description:

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

Treatment:

Drug: TAU