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NCT Number: NCT00939822

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

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.

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Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

40 year–72 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Karen Lazar

Fitchburg, Wisconsin, 53711, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

simvastatin

Drug

40 mg Simvastatin/day

Placebo

Drug

Matching Placebo

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Official study 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

Acronym: SHARP

Important dates

Study start
2009
Primary completion
2013
Study completion
2013
First posted
Jul 15, 2009
Registry last updated
Aug 9, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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