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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG031790-01A1 | U.S. NIH Grant/Contract | View source | |
| H-2009-0030 | Other Identifier | Old IRB Number | |
| H-2008-0275 | Other Identifier | Old IRB Number |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Simvastatin | Experimental | 40 mg. Simvastatin/day |
|
| Placebo | Placebo Comparator | Matching Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin | Drug | 40 mg Simvastatin/day |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cynthia M. Carlsson, MD, MS | UW Madison School of Medicine and Public Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karen Lazar | Fitchburg | Wisconsin | 53711 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34275209 | Derived | 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. | |
| 31607205 | Derived | 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. |
| Label | URL |
|---|---|
| Related Info | View source |
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Screened individuals were not randomized to drug or placebo if they withdrew consent, were unable to complete baseline procedures or no longer met inclusion criteria.
Asymptomatic middle-aged adults (ages 40-72 years) with parental history of AD were recruited from the community through local memory clinics, newsletters, educational talks, booths at health fairs, and newspaper and magazine advertisements.
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| ID | Title | Description |
|---|---|---|
| FG000 | Simvastatin | 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day |
| FG001 | Placebo | Matching Placebo Placebo: Matching Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Simvastatin | 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day |
| BG001 | Placebo | Matching Placebo Placebo: Matching Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | ratio | Baseline and 18 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Simvastatin | 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Cynthia M. Carlsson | University of Wisconsin School of Medicine and Public Health | 608-256-1901 | 11691 | cmc@medicine.wisc.edu |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Drug |
Matching Placebo |
|
| 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. | 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. | Baseline and 18 months |
| Mental health issues |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | 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. | Posted | Mean | 95% Confidence Interval | ratio | Baseline and 18 months |
|
|
|
| Secondary | 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. | Posted | Mean | 95% Confidence Interval | ratio | Baseline and 18 months |
|
|
|
| Secondary | 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. | Posted | Mean | 95% Confidence Interval | ratio | Baseline and 18 months |
|
|
|
| 44 |
| 0 |
| 44 |
| 0 |
| 44 |
| EG001 | Placebo | Matching Placebo Placebo: Matching Placebo | 0 | 44 | 0 | 44 | 0 | 44 |
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |