Simvastatin for mTBI

• Status: Completed
• Trial end date: 2017-06-20
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Office of Research and Development
• Treatments: Pravastatin; Simvastatin

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.