Alzheimer's DiseasePhase 2SHARPNCT00939822
Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease
A Phase 2 study testing Simvastatin in people with Alzheimer's Disease, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The purpose of the research is to see how simvastatin affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal cord. High amounts of beta-amyloid may be associated with a greater risk of getting Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 40 to 72 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Simvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Sep 2013
- 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 40 to 72 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Parent diagnosed with Alzheimer's disease
- Age 40-72
Who cannot join
- Active liver disease
- History of adverse reaction to statins
- Contraindication to lumbar puncture
- Elevated creatine kinase and creatinine lab values
- Use of medications known to interact with statins
- History of dementia or mild cognitive impairment
Show all 14Show fewer
- Currently pregnant or planning to become pregnant
- Use of large quantities of grapefruit juice (more than 1 quart per day)
- Contraindications to MRI (for MRI sub-study)
- Currently on cholesterol-lowering medication or use in past 4 months
- History of heart attack, heart problems, stroke and/or diabetes
- Drinking more than a quart of grapefruit juice per day
- Metal implants, or metal debris in body (MRI)
- List of medications that interact with simvastatin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for AD: "Statins in Healthy, At-Risk Adults: Impact on Amyloid and Regional Perfusion (SHARP)" Study
The purpose of the research is to see how simvastatin affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal cord. High amounts of beta-amyloid may be associated with a greater risk of getting Alzheimer's disease. This study will see if simvastatin can lower the amount of beta-amyloid in the spinal fluid. This study will also see if simvastatin affects memory and thinking, blood flow in the brain, and blood vessel function. The investigators hope that future studies show whether simvastatin might prevent memory loss and decrease the chance of developing Alzheimer's disease.
Read the detailed description
Studies show that some medicines that lower cholesterol may reduce the risk of developing Alzheimer's disease, but this has not yet been proven in humans. We are looking for individuals to participate in this study to see if a cholesterol-lowering medication, called simvastatin affects blood flow to the brain, blood vessel function and a substance in the spinal fluid related to the changes in Alzheimer's disease.
The SHARP study included 88 adults ages 40-72 with parental history of documented Alzheimer's disease. The study had 9 visits over the course of 18 months. Participants had fasting blood tests collected, completed a medical history questionnaire and medication side effect review, underwent lumbar puncture procedure, completed memory testing, and had ultrasound and MRI procedures. Participants were randomly assigned to receive either simvastatin or a placebo each night for 18 months.
- Conditions
- Alzheimer's Disease
- Being tested
- Simvastatin, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
40 mg Simvastatin/day
PlaceboDrug
Matching Placebo
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin | Experimental | 40 mg. Simvastatin/day Receives: Drug: Simvastatin |
| Placebo | Placebo comparator | Matching Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP
Change in CSF beta-amyloid-42 was defined as the ratio of 18-month levels to baseline levels.
Beta-amyloid-42 is a substance found in the plaques in the brain of people with Alzheimer's disease and can be detected in CSF. There is no defined normal range yet for middle-aged adults.
Measured: Baseline and 18 months
Secondary outcomes (3)
Changes in CSF Beta-amyloid-40 Levels as Measured by xMAP (Multi-Analyte Profiling) )
Change in CSF beta-amyloid-40 was defined as the ratio of 18-month levels to baseline levels.
Beta amyloid-40 is a substance found in the brain vessels of individuals with Alzheimer's disease and has more potent cerebrovascular effects on individuals with Alzheimer's disease than any other form of beta amyloid.
Measured: Baseline and 18 months
Changes in CSF Soluble Alpha Precursor Proteins (sAPP-alpha) and Soluble Beta Precursor Proteins (sAPP-beta) as Measured by Duplex
Changes in CSF sAPP-alpha and sAPP-beta were defined as the ratio of 18-month levels to baseline levels.
sAPP-alpha and sAPP-beta are components of beta-amyloid that provide information on beta-amyloid breakdown.
Measured: Baseline and 18 months
Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP
Changes in CSF t-tau and p-tau were defined as the ratio of 18-month levels to baseline levels.
T-tau and p-tau are substances found in the brain that can provide information on nerve cell health in the brain and tangle formation in nerve cells.
Measured: Baseline and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2009 (estimated)
- Study startMar 2009
- Primary completionSep 2013
- Study completionSep 2013
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 Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Cynthia M. Carlsson, MD, MS, Principal investigator, UW Madison School of Medicine and Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00939822
- Sponsor's protocol ID
- 2015-0038
- Other IDs
- R01AG031790-01A1, H-2009-0030, H-2008-0275
- Acronym
- SHARP
- Status last verified
- Aug 2019
- First submitted
- 14 Jul 2009
- Last updated
- 9 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vogt NM, Hunt JFV, Ma Y, Van Hulle CA, Adluru N, Chappell RJ, Lazar KK, Jacobson LE, Austin BP, Asthana S, Johnson SC, Bendlin BB, Carlsson CM. Effects of simvastatin on white matter integrity in healthy middle-aged adults. Ann Clin Transl Neurol. 2021 Aug;8(8):1656-1667. doi: 10.1002/acn3.51421. Epub 2021 Jul 18.
PubMed 34275209Gepner AD, Lazar K, Hulle CV, Korcarz CE, Asthana S, Carlsson CM. Effects of Simvastatin on Augmentation Index Are Transient: Outcomes From a Randomized Controlled Trial. J Am Heart Assoc. 2019 Oct 15;8(20):e009792. doi: 10.1161/JAHA.118.009792. Epub 2019 Oct 12.
PubMed 31607205
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for AD: "Statins in Healthy, At-Risk Adults: Impact on Amyloid and Regional Perfusion (SHARP)" Study
- ClinicalTrials.gov ID
- NCT00939822
- Acronym / sponsor ID
- SHARP / 2015-0038
- Conditions
- Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Mar 2009 (actual)
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 15 Jul 2009 (estimated)
- Results
- Posted 9 Aug 2019
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 the research is to see how simvastatin affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal cord. High amounts of beta-amyloid may be associated with a greater risk of getting Alzheimer's disease. This study will see if simvastatin can lower the amount of beta-amyloid in the spinal fluid. This study will also see if simvastatin affects memory and thinking, blood flow in the brain, and blood vessel function. The investigators hope that future studies show whether simvastatin might prevent memory loss and decrease the chance of developing Alzheimer's disease.
Detailed description
Studies show that some medicines that lower cholesterol may reduce the risk of developing Alzheimer's disease, but this has not yet been proven in humans. We are looking for individuals to participate in this study to see if a cholesterol-lowering medication, called simvastatin affects blood flow to the brain, blood vessel function and a substance in the spinal fluid related to the changes in Alzheimer's disease.
The SHARP study included 88 adults ages 40-72 with parental history of documented Alzheimer's disease. The study had 9 visits over the course of 18 months. Participants had fasting blood tests collected, completed a medical history questionnaire and medication side effect review, underwent lumbar puncture procedure, completed memory testing, and had ultrasound and MRI procedures. Participants were randomly assigned to receive either simvastatin or a placebo each night for 18 months.
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: Simvastatin40 mg. Simvastatin/day |
| Placebo | Placebo comparator | Drug: PlaceboMatching Placebo |
Who may qualify
- Ages
- 40 to 72 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Parent diagnosed with Alzheimer's disease
- Age 40-72
Key exclusion criteria (14 listed)
- Active liver disease
- History of adverse reaction to statins
- Contraindication to lumbar puncture
- Elevated creatine kinase and creatinine lab values
- Use of medications known to interact with statins
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 |
|---|---|---|
| Simvastatin40 mg Simvastatin/day | Drug | Simvastatin |
| PlaceboMatching Placebo | Drug | Placebo |
Primary outcome
Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP
Time frame: Baseline and 18 months
Change in CSF beta-amyloid-42 was defined as the ratio of 18-month levels to baseline levels. Beta-amyloid-42 is a substance found in the plaques in the brain of people with Alzheimer's disease and can be detected in CSF. There is no defined normal range yet for middle-aged adults.
3 secondary outcomes
Changes in CSF Beta-amyloid-40 Levels as Measured by xMAP (Multi-Analyte Profiling) )
Time frame: Baseline and 18 months
Changes in CSF Soluble Alpha Precursor Proteins (sAPP-alpha) and Soluble Beta Precursor Proteins (sAPP-beta) as Measured by Duplex
Time frame: Baseline and 18 months
Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP
Time frame: Baseline and 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34275209Vogt NM, Hunt JFV, Ma Y, Van Hulle CA, Adluru N, Chappell RJ, Lazar KK, Jacobson LE, Austin BP, Asthana S, Johnson SC, Bendlin BB, Carlsson CM. Effects of simvastatin on white matter integrity in healthy middle-aged adults. Ann Clin Transl Neurol. 2021 Aug;8(8):1656-1667. doi: 10.1002/acn3.51421. Epub 2021 Jul 18.
- Derived from this study: PubMed 31607205Gepner AD, Lazar K, Hulle CV, Korcarz CE, Asthana S, Carlsson CM. Effects of Simvastatin on Augmentation Index Are Transient: Outcomes From a Randomized Controlled Trial. J Am Heart Assoc. 2019 Oct 15;8(20):e009792. doi: 10.1161/JAHA.118.009792. Epub 2019 Oct 12.
- Related InfoLink 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
UW Madison School of Medicine and Public Health
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's 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 14 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 9 Aug 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 9 Aug 2019). 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?
Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP (time frame: Baseline and 18 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 NCT00939822, 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 9 Aug 2019.