Alzheimer DiseasePhase 2ESPRITNCT00486044
Evaluating Simvastatin's Potential Role in Therapy
A Phase 2 study testing Simvastatin in people with Alzheimer Disease, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The purpose of this study is to see how simvastatin, a cholesterol-lowering drug, affects processes related to the development of Alzheimer's disease, including: 1) levels of a substance called beta-amyloid-42 found in the spinal fluid surrounding the brain, 2) blood flow in the brain, 3) inflammation in the brain… Read more about this study
- Who is it for?
- Ages 35 to 69 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2005to Jun 2009
- Phase
- Phase 2
- 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 35 to 69 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 35 to 69
- Parent with Alzheimer's disease
Who cannot join
- Current use of cholesterol-lowering medication
- Active liver disease
- History of adverse reaction to statins
- Contraindication to lumbar puncture
- Elevated lab values (creatine kinase and creatinine)
- Use of medications known to interact with statins
Show all 12Show fewer
- History of dementia
- Currently pregnant or planning to become pregnant
- Use of large quantities of grapefruit juice (more than 1 quart per day)
- Current involvement in another investigational drug study
- Contraindications to MRI (for MRI sub-study)
- Ethical contraindication to placebo (persons with high vascular risk)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Statins on Pathobiology of Alzheimer's Disease
The purpose of this study is to see how simvastatin, a cholesterol-lowering drug, affects processes related to the development of Alzheimer's disease, including: 1) levels of a substance called beta-amyloid-42 found in the spinal fluid surrounding the brain, 2) blood flow in the brain, 3) inflammation in the brain, and 4) cognitive function.
Read the detailed description
Some studies suggest that statin medications, which are a group of cholesterol-lowering medicines, may help prevent Alzheimer's disease. However, this has not been proven in humans. The purpose of this study is to see how simvastatin affects a substance in the spinal fluid around the brain called beta-amyloid-42 which is thought to contribute to Alzheimer's disease. This study also evaluates whether simvastatin improves regional brain blood flow (on magnetic resonance imaging [MRI]), reduces inflammation, and improves cognitive function.
The ESPRIT study was a 9-month randomized, controlled clinical trial that randomized 100 middle-aged adults with a parental history of Alzheimer's disease. Participants were randomized to simvastatin 40 mg for one month then 80 mg daily or matching placebo tablets. Fifty of the ESPRIT subjects participated in the MRI sub-study.
Participants had the following data collected: fasting blood tests (baseline and months 3 and 9), medical history and medication questionnaires (each visit), study medication side effect review (all visits), lumbar puncture procedure (baseline and month 9), memory testing (baseline and months 3 and 9), and MRI (baseline and month 9 in 50 sub-study participants).
- Conditions
- Alzheimer Disease
- Being tested
- Simvastatin, Placebo
- Keywords
- amyloid protein, apolipoprotein, cerebrospinal fluid, cerebrovascular circulation, inflammation, magnetic resonance imaging, prevention & control
- Medical subject headings
- Alzheimer Disease, Amyloidosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Zocor
40 mg tablet each night for one month, then 80 mg for 8 months
PlaceboDrug
Matching tablet each night for 9 months
| Study group | Role | What they receive |
|---|---|---|
| simvastatin | Experimental | simvastatin 40 mg nightly for 1 month then 80 mg nightly for 8 months Receives: Drug: Simvastatin |
| Placebo | Placebo comparator | Matching placebo tablet nightly for 9 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42
Measured: baseline and 9 months
Secondary outcomes (3)
Changes in Regional Cerebral Blood Flow on MRI
Mean changes noted in posterior cingulate cortex
Measured: baseline and 9 months
Change in Inflammatory Markers
Change noted in serum high-sensitivity c-reactive protein
Measured: baseline and 9 months
Changes in Cognitive Performance
Change in Hopkins Verbal Learning Test Delayed Recall
The Hopkins Verbal Learning Test Delayed Recall score is the raw number of words recalled at Trial 4, adjusted for years of education and age. This is a 12-item word list test.
Measured: Baseline and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2007 (estimated)
- Study startFeb 2005
- Primary completionJun 2009
- Study completionJun 2009
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 (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), Paul Beeson Faculty Scholars Program, The John A. Hartford Foundation, The Atlantic Philanthropies, Starr Foundation, American Federation for Aging Research, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Cynthia M. Carlsson, MD, MS, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00486044
- Sponsor's protocol ID
- IA0116
- Other IDs
- 1K23AG026752-01
- Acronym
- ESPRIT
- Status last verified
- Feb 2019
- First submitted
- 12 Jun 2007
- Last updated
- 5 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61. doi: 10.1073/pnas.081620098. Epub 2001 Apr 10.
PubMed 11296263Wolozin B. A fluid connection: cholesterol and Abeta. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5371-3. doi: 10.1073/pnas.101123198. No abstract available.
PubMed 11344276Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology. 2005 Mar;234(3):851-9. doi: 10.1148/radiol.2343040197.
PubMed 15734937
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Statins on Pathobiology of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00486044
- Acronym / sponsor ID
- ESPRIT / IA0116
- Conditions
- Alzheimer Disease
- Keywords
- amyloid protein, apolipoprotein, cerebrospinal fluid, cerebrovascular circulation, inflammation, magnetic resonance imaging, prevention & control
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), Paul Beeson Faculty Scholars Program, The John A. Hartford Foundation, The Atlantic Philanthropies, Starr Foundation, American Federation for Aging Research, Merck Sharp & Dohme LLC
- Study start
- Feb 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 13 Jun 2007 (estimated)
- Results
- Posted 5 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see how simvastatin, a cholesterol-lowering drug, affects processes related to the development of Alzheimer's disease, including: 1) levels of a substance called beta-amyloid-42 found in the spinal fluid surrounding the brain, 2) blood flow in the brain, 3) inflammation in the brain, and 4) cognitive function.
Detailed description
Some studies suggest that statin medications, which are a group of cholesterol-lowering medicines, may help prevent Alzheimer's disease. However, this has not been proven in humans. The purpose of this study is to see how simvastatin affects a substance in the spinal fluid around the brain called beta-amyloid-42 which is thought to contribute to Alzheimer's disease. This study also evaluates whether simvastatin improves regional brain blood flow (on magnetic resonance imaging [MRI]), reduces inflammation, and improves cognitive function.
The ESPRIT study was a 9-month randomized, controlled clinical trial that randomized 100 middle-aged adults with a parental history of Alzheimer's disease. Participants were randomized to simvastatin 40 mg for one month then 80 mg daily or matching placebo tablets. Fifty of the ESPRIT subjects participated in the MRI sub-study.
Participants had the following data collected: fasting blood tests (baseline and months 3 and 9), medical history and medication questionnaires (each visit), study medication side effect review (all visits), lumbar puncture procedure (baseline and month 9), memory testing (baseline and months 3 and 9), and MRI (baseline and month 9 in 50 sub-study participants).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| simvastatin | Experimental | Drug: Simvastatinsimvastatin 40 mg nightly for 1 month then 80 mg nightly for 8 months |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo tablet nightly for 9 months |
Who may qualify
- Ages
- 35 to 69 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 35 to 69
- Parent with Alzheimer's disease
Key exclusion criteria (12 listed)
- Current use of cholesterol-lowering medication
- Active liver disease
- History of adverse reaction to statins
- Contraindication to lumbar puncture
- Elevated lab values (creatine kinase and creatinine)
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: Zocor40 mg tablet each night for one month, then 80 mg for 8 months | Drug | simvastatin |
| PlaceboMatching tablet each night for 9 months | Drug | Placebo |
Primary outcome
Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42
Time frame: baseline and 9 months
3 secondary outcomes
Changes in Regional Cerebral Blood Flow on MRI
Time frame: baseline and 9 months
Change in Inflammatory Markers
Time frame: baseline and 9 months
Changes in Cognitive Performance
Time frame: Baseline and 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11296263Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61. doi: 10.1073/pnas.081620098. Epub 2001 Apr 10.
- Background: PubMed 11344276Wolozin B. A fluid connection: cholesterol and Abeta. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5371-3. doi: 10.1073/pnas.101123198. No abstract available.
- Background: PubMed 15734937Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology. 2005 Mar;234(3):851-9. doi: 10.1148/radiol.2343040197.
- Wisconsin Alzheimer's Disease Research CenterLink provided by the sponsor.
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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.
Cynthia M. Carlsson, MD, MS principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simvastatin in people with Alzheimer Disease, run by University of Wisconsin, Madison 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 2 inclusion and 12 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 5 Mar 2019. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 5 Nov 2015). 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?
Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42 (time frame: baseline and 9 months). 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 NCT00486044, which also lists 3 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 5 Mar 2019.