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Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease (SHARP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00939822
Recruitment Status : Completed
First Posted : July 15, 2009
Results First Posted : August 9, 2019
Last Update Posted : August 9, 2019
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Simvastatin Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : March 2009
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Arm Intervention/treatment
Experimental: Simvastatin
40 mg. Simvastatin/day
Drug: Simvastatin
40 mg Simvastatin/day

Placebo Comparator: Placebo
Matching Placebo
Drug: Placebo
Matching Placebo

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Changes in CSF Beta-amyloid-40 Levels as Measured by xMAP (Multi-Analyte Profiling) ) [ Time Frame: Baseline and 18 months ]

    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.

  2. 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 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.

  3. Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP [ Time Frame: Baseline and 18 months ]

    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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years to 72 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Parent diagnosed with Alzheimer's disease
  • Age 40-72

Exclusion Criteria:

  • 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
  • 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

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 identifier (NCT number): NCT00939822

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United States, Wisconsin
Karen Lazar
Fitchburg, Wisconsin, United States, 53711
Sponsors and Collaborators
University of Wisconsin, Madison
National Institute on Aging (NIA)
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Principal Investigator: Cynthia M. Carlsson, MD, MS UW Madison School of Medicine and Public Health
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Wisconsin, Madison Identifier: NCT00939822    
Other Study ID Numbers: 2015-0038
R01AG031790-01A1 ( U.S. NIH Grant/Contract )
H-2009-0030 ( Other Identifier: Old IRB Number )
H-2008-0275 ( Other Identifier: Old IRB Number )
First Posted: July 15, 2009    Key Record Dates
Results First Posted: August 9, 2019
Last Update Posted: August 9, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors