Simvastatin for mTBI

NCT01952288 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: B1195-I
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

TBI-Traumatic Brain Injury

Outcome Measures

Primary Outcomes (2)

• Cerebrospinal Fluid (CSF) T-tau Concentration

  Change in CSF total tau concentration from baseline to 12 months of study drug treatment

  baseline, 12 months

• 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 Outcomes (2)

• CSF Abeta 1-40 Concentration

  baseline, 12 months

• CSF Abeta 1-42 Concentration

  baseline, 12 months

Study Arms (2)

simvastatin

EXPERIMENTAL

simvastatin 40 mg/day

Drug: simvastatin

placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo Oral Tablet

Interventions

simvastatin DRUG

simvastatin 40 mg/day for 12 months

Also known as: Zocor

simvastatin

Placebo Oral Tablet DRUG

placebo comparator

placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108, United States

Location

Related Publications (2)

• 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. doi: 10.3233/jad-2006-10408.

  PMID: 17183151 BACKGROUND

• 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.

  PMID: 28821686 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Recruitment difficulties (persons with normal cholesterol levels were not interested in taking statins) led to not enrolling sufficient numbers of participants to achieve target power.

Results Point of Contact

• Title: Rebekah J. Rein, JD
• Organization: VA Puget Sound Health Care System

rebekah.rein@va.gov

206-764-2711

Study Officials

• Elaine R Peskind, MD

  VA Puget Sound Health Care System Seattle Division, Seattle, WA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: September 27, 2013
• Study Start: September 16, 2013
• Primary Completion: June 20, 2017
• Study Completion: June 20, 2017
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)