Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol
Condition: Traumatic Brain Injury; Post-traumatic Stress Disorder
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Atorvastatin; Placebo
Intervention description: In this Phase II randomized clinical trial of 200 MTBI subjects to evaluate atorvastatin as a neuroprotective agent, subjects will receive either active drug or placebo (1:1 randomization) for 7 days, starting within 24 hours of the brain injury. The dosage for subjects in the treatment group will be weight-based at 1mg/kgm, up to 80 mg, which will be the maximal dose. Subjects will be monitored at 3-4 days after injury by phone, then with follow-up visits at 1 week, 1 month, 3 months.; In this Phase II randomized clinical trial of 200 MTBI subjects to evaluate atorvastatin as a neuroprotective agent, subjects will receive either active drug or placebo (1:1 randomization) for 7 days, starting within 24 hours of the brain injury. For the placebo group, subjects will take a daily dose of an inert preparation, visually indistinguishable from the active agent. They will take this preparation for seven days, started within 24 hours of MTBI, and their outcome will be compared with the group of subjects receiving active drug. Subjects will be monitored at 3-4 days after injury by phone, then with follow-up visits at 1 week, 1 month, 3 months.
Intervention MeSH terms: Atorvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: mild traumatic brain injury; post-concussion syndrome; acute stress disorder; post-traumatic stress disorder; atorvastatin

Summary:

      The purpose of this study is to improve the ability to diagnose problems after mild traumatic
      brain injury (MTBI) and to test a drug that may improve the outcome from these injuries. Of
      the more than 1.5 million people who experience a traumatic brain injury (TBI) each year in
      the United States, as many as 75% sustain a mild TBI which can cause long-term or permanent
      impairments/disabilities in a significant proportion of patients. In addition, traumatic
      brain injury has become a signature injury of the wars in Iraq and Afghanistan. For people
      with these injuries, it is difficult to determine whether symptoms are due to the head injury
      or another condition, such as Post-traumatic Stress Disorder. In this project, there are 3
      observational studies that involve testing of mental functions and behavior, imaging of the
      brain with special x-ray procedures, and blood samples to look at glandular function, which
      may be affected by head injury. A fourth study is a test of a drug, atorvastatin, which may
      provide protection for injured brain cells and improve outcome. By collecting and analyzing
      the information from these tests, it will be possible to make the process of diagnosing mild
      TBI or post traumatic stress disorder (PTSD) more precise, and also to see if atorvastatin is
      a helpful drug for patients with MTBI.
    

Eligibility criteria:

        Inclusion Criteria:

          -  age 18-50 years

          -  MTBI subjects: evidence of closed head injury; Glasgow Coma Score 13-15; loss of
             consciousness < 30 minutes; post-traumatic amnesia < 24 hours; Abbreviated Injury
             Score </= 3 for any body region; absence of focal lesions on head CT scan

          -  Orthopedic Injury subjects: evidence of traumatic injury, other than head; Abbreviated
             Injury Score </= 3 for any body region

          -  does not require hospitalization for injuries

          -  visual acuity and hearing adequate to participate in testing

          -  fluent in either English or Spanish

        Exclusion Criteria:

          -  Abbreviated Injury Score > 3 for any body region

          -  any type of penetrating injury

          -  history of significant pre-existing disease or systemic injuries

          -  history of schizophrenia or bipolar disorder

          -  blood alcohol > 200 mL/dL

          -  left-handed

          -  existing contraindications for MRI

          -  claustrophobia

          -  pregnancy

          -  exclusions related to atorvastatin, including currently taking any statin drug
             (atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin), no
             longer taking a statin drug but history of use within the last six months, previously
             taking any statin drug at any time but now discontinued due to side effects, taking
             any medication with known interactions with atorvastatin (cyclosporine, fibric acid
             derivative, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or
             lopinavir, niacin in doses exceeding multivitamin dosage, or azole antifungals),
             active liver disease, history of unexplained persistent elevation of serum
             transaminases, and hypersensitivity to any component of atorvastatin.