Clinical trial NCT00939822: Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2009-07-15
Enrollment: 88
Sex: ALL
Minimum age (years): 40
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP
timeFrame: Baseline and 18 months
Secondary outcomes:
measure: Changes in CSF Beta-amyloid-40 Levels as Measured by xMAP (Multi-Analyte Profiling) )
timeFrame: Baseline and 18 months
measure: Changes in CSF Soluble Alpha Precursor Proteins (sAPP-alpha) and Soluble Beta Precursor Proteins (sAPP-beta) as Measured by Duplex
timeFrame: Baseline and 18 months
measure: Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP
timeFrame: Baseline and 18 months
Other outcomes:
Locations:
city: Fitchburg
country: United States
facility: Karen Lazar
state: Wisconsin
Study officials:
affiliation: UW Madison School of Medicine and Public Health
name: Cynthia M. Carlsson, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Gepner 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.