TBI-Traumatic Brain Injury Clinical Trial
Official title:
Simvastatin: Proof-of-Concept for Prevention of Neurodegeneration in Mild TBI
| Verified date | November 2021 |
| Source | VA Office of Research and Development |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 5 |
| Est. completion date | June 20, 2017 |
| Est. primary completion date | June 20, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 21 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | VA Puget Sound Health Care System Seattle Division, Seattle, WA | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| VA Office of Research and Development |
United States,
Li G, Mayer CL, Morelli D, Millard SP, Raskind WH, Petrie EC, Cherrier M, Fagan AM, Raskind MA, Peskind ER. Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults. Neurology. 2017 Sep 19;89(12):1251-1255. doi: 10.1212/WNL.0000000000004392. Epub 2017 Aug 18. — View Citation
Riekse RG, Li G, Petrie EC, Leverenz JB, Vavrek D, Vuletic S, Albers JJ, Montine TJ, Lee VM, Lee M, Seubert P, Galasko D, Schellenberg GD, Hazzard WR, Peskind ER. Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid. J Alzheimers Dis. 2006 Dec;10(4):399-406. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Cerebrospinal Fluid (CSF) T-tau Concentration | Change in CSF total tau concentration from baseline to 12 months of study drug treatment | baseline, 12 months | |
| Primary | Cerebrospinal Fluid (CSF) P-tau 181 Concentration | Change in CSF p-tau 181 concentration from baseline to 12 months of study drug treatment | baseline, 12 months | |
| Secondary | CSF Abeta 1-40 Concentration | change in CSF abeta 1-40 concentration from baseline to 12 months of study drug treatment | baseline, 12 months | |
| Secondary | CSF Abeta 1-42 Concentration | change in CSF abeta 1-42 concentration from baseline to 12 months of study drug treatment | baseline, 12 months |