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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 88
- Locations
- 1
- Primary Endpoint
- Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP
Study Overview
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.
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
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to 72 Years (Adult, Older Adult)
- Sex
- 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
Arms & Interventions
Simvastatin
40 mg. Simvastatin/day
Intervention: Simvastatin (Drug)
Placebo
Matching Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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
- Changes in CSF Beta-amyloid-40 Levels as Measured by xMAP (Multi-Analyte Profiling) )(Baseline and 18 months)
- Changes in CSF Soluble Alpha Precursor Proteins (sAPP-alpha) and Soluble Beta Precursor Proteins (sAPP-beta) as Measured by Duplex(Baseline and 18 months)
- Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP(Baseline and 18 months)