Simvastatin for mTBI
Condition: TBI-Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Intervention: simvastatin; Placebo Oral Tablet
Intervention description: simvastatin 40 mg/day for 12 months; placebo comparator
Intervention MeSH terms: Simvastatin
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      Study of simvastatin in Iraq/Afghanistan Veterans with multiple blast exposure and mTBI. The
      study will measure substances in cerebrospinal fluid (CSF) that are related to dementing
      disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females ages 21-50 years.

          -  Documented hazardous duty in Iraq and or Afghanistan with the U.S. Armed Forces.

          -  Exposure to one or more blast trauma events resulting in mTBI according to American
             Congress of Rehabilitation Medicine (ACRM) criteria.

          -  More than 6 months since last blast trauma exposure

          -  Ability to complete psychometric and other clinical assessments in English (i.e.,
             adequate English language skills, vision and hearing).

          -  elevated cholesterol levels, i.e. total cholesterol >200 and/or LDL >130. This would
             generally prompt the initiation of a lipid-lowering agent as standard care in the
             general medical community.

          -  No use of statins during the previous year and no recent (past 4 weeks) use of other
             lipid-lowering drugs (e.g., fibrates, niacin > 500mg/d, or high dose omega-3 fatty
             acids) preceding randomization.

          -  No clinically significant laboratory abnormalities (electrolytes, glucose, carbon
             dioxide, blood urea nitrogen (BUN), creatinine, vitamin B12, folate, albumin, thyroid
             stimulating hormone).

          -  Platelet count > 100,000/mm2.

          -  Body Mass Index (BMI) between 18 and 36 inclusive

        Exclusion Criteria:

          -  History of head trauma with loss of consciousness (LOC)>30 minutes, or with a
             penetrating head wound, or with moderate to severe memory or other cognitive
             impairment.

          -  Neurological disorders: multiple sclerosis, epilepsy, stroke, Parkinson's disease
             (PD), other degenerative Central Nervous System (CNS) disorders, or neuropathy with
             radicular involvement.

          -  Acute or chronic major psychiatric disorders: schizophrenia, bipolar disorder or
             severe major depressive disorder, or severe anxiety disorder except PTSD and panic
             disorder (PTSD and depressive symptoms are common co-morbid conditions for combat mTBI
             and a subset of these patients have symptoms consistent with panic disorder as well).

          -  Use of illegal drugs; alcohol abuse within the past 6 months.

          -  Poorly controlled hypertension, heart failure, coronary heart disease, peripheral
             artery disease, carotid artery disease, diabetes mellitus, pulmonary disease with
             hypoxia or hypercapnia, significant hepatic disease or hepatitis C seropositivity,
             renal failure, treatment for cancer, HIV positive, active infectious disease or
             presence of abdominal aortic aneurysm.

          -  Contraindications to lumbar puncture (LP) (e.g., spinal cord injury; deformity, severe
             disease or infection in the region of the lumbosacral spine; bleeding tendency, use of
             anticoagulant medications, or platelet count <100,000/mm2).

          -  Receiving medication in an investigational drug study.

          -  Exclusionary medications (used in the 4 weeks prior to screening):

          -  Fibrates and niacin due to increased risk for myopathy in combination with statins;

          -  Potential drug-drug interactions with statins via effects on CYP3A4: itraconazole,
             ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone,
             amiodarone, cyclosporine, isoniazid, quinidine, or large quantities of grapefruit
             juice (>1 quart daily);

          -  Selected CNS-acting medications: antipsychotics, anti-Parkinson's disease medications
             and CNS stimulants

          -  Other medications affecting coagulation and/or inflammation: coumadin, potent
             anti-inflammatory medications (hydrocortisone, methotrexate or other potent
             immune-modulating medications), and anti-HIV medications.

          -  All female subjects of childbearing potential will undergo a urine pregnancy test at
             every subject visit; subjects with positive pregnancy test results will be excluded.
             In addition, all female subjects of childbearing potential will be required to use a
             reliable method of contraception throughout the duration of the study.