TBI-Traumatic Brain InjuryPhase 4NCT01952288
Simvastatin for mTBI
A Phase 4 study testing simvastatin in people with TBI-Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- TBI-Traumatic Brain Injury
- What is being tested?
- simvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2013to 20 Jun 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108
About this study
Official title: Simvastatin: Proof-of-Concept for Prevention of Neurodegeneration in Mild TBI
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.
Read the 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.
- Conditions
- TBI-Traumatic Brain Injury
- Being tested
- simvastatin, Placebo Oral Tablet
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
simvastatinDrug
Also called Zocor
simvastatin 40 mg/day for 12 months
Placebo Oral TabletDrug
placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| simvastatin | Experimental | simvastatin 40 mg/day Receives: Drug: simvastatin |
| placebo | Placebo comparator | placebo Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebrospinal Fluid (CSF) T-tau Concentration
Change in CSF total tau concentration from baseline to 12 months of study drug treatment
Measured: 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
Measured: baseline, 12 months
Secondary outcomes (2)
CSF Abeta 1-40 Concentration
change in CSF abeta 1-40 concentration from baseline to 12 months of study drug treatment
Measured: baseline, 12 months
CSF Abeta 1-42 Concentration
change in CSF abeta 1-42 concentration from baseline to 12 months of study drug treatment
Measured: baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2013 (estimated)
- Study start16 Sep 2013
- Primary completion20 Jun 2017
- Study completion20 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TBI-Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Elaine R Peskind, MD, Principal investigator, VA Puget Sound Health Care System Seattle Division, Seattle, WA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01952288
- Sponsor's protocol ID
- B1195-I
- Status last verified
- Nov 2021
- First submitted
- 24 Sep 2013
- Last updated
- 15 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 17183151Li 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.
PubMed 28821686
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Simvastatin: Proof-of-Concept for Prevention of Neurodegeneration in Mild TBI
- ClinicalTrials.gov ID
- NCT01952288
- Acronym / sponsor ID
- B1195-I
- Conditions
- TBI-Traumatic Brain Injury
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 16 Sep 2013 (actual)
- Primary completion
- 20 Jun 2017 (actual)
- Study completion
- 20 Jun 2017 (actual)
- First posted
- 27 Sep 2013 (estimated)
- Results
- Posted 15 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| simvastatin | Experimental | Drug: simvastatinsimvastatin 40 mg/day |
| placebo | Placebo comparator | Drug: Placebo Oral Tabletplacebo |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| simvastatinAlso: Zocorsimvastatin 40 mg/day for 12 months | Drug | simvastatin |
| Placebo Oral Tabletplacebo comparator | Drug | placebo |
Primary outcome
Cerebrospinal Fluid (CSF) T-tau Concentration
Time frame: baseline, 12 months
Change in CSF total tau concentration from baseline to 12 months of study drug treatment
Cerebrospinal Fluid (CSF) P-tau 181 Concentration
Time frame: baseline, 12 months
Change in CSF p-tau 181 concentration from baseline to 12 months of study drug treatment
2 secondary outcomes
CSF Abeta 1-40 Concentration
Time frame: baseline, 12 months
CSF Abeta 1-42 Concentration
Time frame: baseline, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17183151Riekse 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.
- Background: PubMed 28821686Li 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elaine R Peskind, MD principal investigator
VA Puget Sound Health Care System Seattle Division, Seattle, WA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing simvastatin in people with TBI-Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebrospinal Fluid (CSF) T-tau Concentration (time frame: baseline, 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01952288, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.