Trial Outcomes & Findings for Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease (NCT NCT00939822)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

Baseline and 18 months

Results posted on

2019-08-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Simvastatin 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo Matching Placebo Placebo: Matching Placebo
Overall Study STARTED	44	44
Overall Study COMPLETED	42	41
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Simvastatin 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo Matching Placebo Placebo: Matching Placebo
Overall Study Lost to Follow-up	1	0
Overall Study withdrew from study due to busy schedule	1	1
Overall Study Mental health issues	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Simvastatin n=44 Participants 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo n=44 Participants Matching Placebo Placebo: Matching Placebo	Total n=88 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	38 Participants n=7 Participants	79 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	55.95 years STANDARD_DEVIATION 6.2 • n=5 Participants	54.4 years STANDARD_DEVIATION 7.8 • n=7 Participants	55.21 years STANDARD_DEVIATION 6.99 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	44 participants n=5 Participants	44 participants n=7 Participants	88 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Simvastatin n=39 Participants 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo n=40 Participants Matching Placebo Placebo: Matching Placebo
Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP	1.01 ratio Interval 0.96 to 1.07	0.98 ratio Interval 0.95 to 1.02

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Simvastatin n=39 Participants 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo n=40 Participants Matching Placebo Placebo: Matching Placebo
Changes in CSF Beta-amyloid-40 Levels as Measured by xMAP (Multi-Analyte Profiling) )	1.03 ratio Interval 0.99 to 1.07	0.98 ratio Interval 0.94 to 1.01

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Simvastatin n=39 Participants 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo n=40 Participants Matching Placebo Placebo: Matching Placebo
Changes in CSF Soluble Alpha Precursor Proteins (sAPP-alpha) and Soluble Beta Precursor Proteins (sAPP-beta) as Measured by Duplex sAPP-alpha	0.96 ratio Interval 0.92 to 1.0	1.03 ratio Interval 0.97 to 1.09
Changes in CSF Soluble Alpha Precursor Proteins (sAPP-alpha) and Soluble Beta Precursor Proteins (sAPP-beta) as Measured by Duplex sAPP-beta	0.98 ratio Interval 0.93 to 1.02	1.00 ratio Interval 0.97 to 1.04

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Simvastatin n=39 Participants 40 mg. Simvastatin/day Simvastatin: 40 mg Simvastatin/day	Placebo n=40 Participants Matching Placebo Placebo: Matching Placebo
Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP Total tau	1.01 ratio Interval 0.97 to 1.05	1.01 ratio Interval 0.98 to 1.05
Changes in CSF Total Tau (T-tau) and Phosphorylated Tau (P-tau) as Measured by xMAP Phosphorylated tau	1.16 ratio Interval 0.9 to 1.42	1.15 ratio Interval 1.0 to 1.29

Adverse Events

Simvastatin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Cynthia M. Carlsson

University of Wisconsin School of Medicine and Public Health

Phone: 608-256-1901

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place