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Simvastatin for mTBI

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ClinicalTrials.gov Identifier: NCT01952288
Recruitment Status : Completed
First Posted : September 27, 2013
Last Update Posted : June 29, 2018
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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.

Condition or disease Intervention/treatment Phase
TBI-Traumatic Brain Injury Drug: simvastatin Drug: Placebo Oral Tablet Phase 4

Detailed Description:

Many Iraq and Afghanistan Veterans have experienced repetitive blast exposure mild traumatic brain injury (mTBI) with persistent cognitive, emotional, and neurological postconcussive symptoms. There is an urgent need to develop effective treatments to reduce both the intensity of these Veterans' current symptoms as well as their potential long-term risks for developing neurodegenerative dementing disorders related to repetitive mTBI: chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD). Converging evidence suggests that statins may possess neuroprotective effects against pathologic processes related to tau protein metabolism that appear to be a common feature of CTE, AD, and other neurodegenerative sequelae of repetitive mTBI.

The investigators propose a 12-month, double-blind, randomized, active-drug-controlled trial to establish proof-of-concept for use of simvastatin (40 mg/d) for decreasing CSF biomarkers of neurodegeneration and increasing CSF neurotrophins in 120 Iraq and Afghanistan Veterans with repetitive blast trauma mTBI.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Simvastatin: Proof-of-Concept for Prevention of Neurodegeneration in Mild TBI
Actual Study Start Date : September 16, 2013
Actual Primary Completion Date : June 20, 2017
Actual Study Completion Date : June 20, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

Arm Intervention/treatment
Experimental: simvastatin
simvastatin 40 mg/day
Drug: simvastatin
simvastatin 40 mg/day for 12 months
Other Name: Zocor

Placebo Comparator: placebo Drug: Placebo Oral Tablet
placebo comparator




Primary Outcome Measures :
  1. cerebrospinal fluid (CSF) tau concentration [ Time Frame: baseline, 12 months post-treatment ]
    Change in CSF tau concentration


Secondary Outcome Measures :
  1. Concentration of cerebrospinal fluid (CSF) Brain-derived neurotrophic factor (BDNF) [ Time Frame: Baseline, 12 months post-treatment ]
    Change in CSF BDNF concentration



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01952288


Locations
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United States, Washington
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, United States, 98108
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Elaine R Peskind, MD VA Puget Sound Health Care System Seattle Division, Seattle, WA

Publications:
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01952288     History of Changes
Other Study ID Numbers: B1195-I
First Posted: September 27, 2013    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors