Traumatic Brain Injury
Conditions
Brief summary
The purpose of this study is to determine if experimental drug treatment improves recovery after TBI as compared to a control (placebo) group. Changes in recovery will be measured throughout the study. The study drugs listed below are approved by the U.S. Food and Drug Administration (FDA) but are being used off-label in this study. This means that the drugs are not currently approved to treat TBI.
Interventions
DRUGAtorvastatin Calcium
Capsule, 80 mg/day, with no loading dose, for 28 days
Capsule, 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
DRUGCandesartan Cilexetil
Capsule, 8 mg once on Day 1, then 16 mg daily for 27 days
DRUGPlacebo
Capsule, 2x/day for 28 days
Sponsors
United States Department of Defense
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults (18-65 years of age, inclusive) 2. Presents to a participating enrollment site and is able to receive first dose within 24 hours of non-penetrating head injury warranting clinical evaluation with a non-contrast head CT based on American College of Emergency Physicians (ACEP) Centers for Disease Control and Prevention (CDC) clinical policy for TBI imaging. 3. Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15 4. Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+) 5. Initial Glial Fibrillary Acidic Protein (GFAP) blood level \>100 pg/ml ≤ 15,000 pg/ml determined using a for Research Use Only (RUO) assay(s) or an Investigation Use Only (IUO) assay(s) 6. Persons of childbearing potential (i.e., those not postmenopausal or surgically sterile) may participate provided that they are using adequate birth control methods for the duration of investigational product administration (see manual of procedures for adequate birth control methods) 7. Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications 8. Participants or legally authorized representative (LAR) willing and able to provide informed consent 9. Participants or LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the informed consent form (ICF) 10. Willingness and ability to comply with all study procedures, treatment, and follow-up
Exclusion criteria
1. Isolated epidural hematoma 2. Pre-existing conditions including disabling developmental, neurologic, psychiatric, medical disorder that continues to produce functional disability up to the time of injury; or imminent death based on clinical judgement 3. Current enrollment in another interventional study 4. Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months 5. Current incarceration or in custody 6. Currently prescribed one of the investigational products (or other drugs in the same class) prior to injury; or contra-indicated or as listed in the appendices 7. Hypersensitivity or intolerance to investigational products or the investigational products' respective classes 8. Renal dysfunction (Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (\<60 mL/minute/1.73 m2) 9. Acute liver disease or hepatic dysfunction (ALT/AST \>3 times upper limit of normal lab value) 10. Hemodynamic instability, per participating site physician investigator clinical judgment 11. Inability to swallow investigational product capsule 12. Unable or unwilling to consume animal byproducts, has a gelatin allergy, and/or religious beliefs that do not permit consuming gelatin 13. Intolerance to small amounts of lactose (less than ½ teaspoonful) daily 14. Low likelihood of follow up or study compliance, or any other reason, in the opinion of the participating site investigator, the participants should not participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glasgow Outcome Scale-Extended (GOSE 2-Way) | 2 weeks to 3 months postinjury | Functional impairment due only to the TBI will be measured using the GOSE Scale-Extended (GOSE 2-Ways). The score ranges from 1-8, with higher scores indicating better recovery. Change will be measured from Week 2 to Month 3 postinjury and compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood-based biomarkers (Neurofilament light chain) | Week 2 | Neurofilament light chain (NfL) levels postinjury in participants with TBI will be measured and compared to placebo |
| Blood-based biomarker (GFAP) | Week 2 | GFAP levels postinjury in participants with TBI as compared to placebo |
| Imaging biomarkers | 2 weeks to 3 months postinjury | Comparison of MRI diffusion tensor imaging (DTI) Axial Diffusivity (AD) measure using the average of 4 long association/projections tracts: (i) Anterior Limb of Internal Capsule (ALIC); (ii) External Capsule (EC); (iii) Superior Corona Radiata (SCR); and (iv) Superior Longitudinal Fasciculus (SLF). Change will be measured from 2 Weeks to 3 Months postinjury. |
| Post-TBI cognitive outcome (BTACT) | Day 3 to Week 4 postinjury | Neurocognitive impairment due to TBI will be measured using the Brief Test of Adult Cognition by Telephone (BTACT). Change will be measured by composite z-score from Day 3 to Week 4 postinjury |
| Post-TBI symptom outcome (Rivermead) | Day 3 to Week 4 | Post-concussive symptoms due to TBI as measured by the change in Rivermead Post Concussion Symptoms Questionnaire (RPQ) Total score (0-64) from Day 3 to Week 4. Higher scores indicate more severe symptoms |
Countries
United States
Outcome results
None listed