Trial Outcomes & Findings for Evaluating Simvastatin's Potential Role in Therapy (NCT NCT00486044)

NCT ID: NCT00486044

Last Updated: 2019-03-05

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

103 participants

Primary outcome timeframe

baseline and 9 months

Results posted on

2019-03-05

Participant Flow

Middle-aged adults with parental history of Alzheimer's disease were recruited for this single-site trial (Madison, Wisconsin) from the Wisconsin Registry for Alzheimer's Prevention (WRAP) or the community through newsletters, websites, educational talks, health fairs, local clinics, and newspaper and magazine advertisements.

103 participants enrolled in the trial and 100 were randomized to treatment (1 no longer met inclusion criteria, 2 declined participation).

Participant milestones

Participant milestones
Measure	Simvastatin Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo Matching placebo tablet nightly for 9 months
Overall Study STARTED	51	49
Overall Study COMPLETED	49	46
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Simvastatin Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo Matching placebo tablet nightly for 9 months
Overall Study Withdrawal by Subject	2	1
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Evaluating Simvastatin's Potential Role in Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Simvastatin n=51 Participants Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo n=49 Participants Matching placebo tablet nightly for 9 months	Total n=100 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	49 Participants n=5 Participants	42 Participants n=7 Participants	91 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	53.3 years STANDARD_DEVIATION 7.4 • n=5 Participants	52.4 years STANDARD_DEVIATION 8.5 • n=7 Participants	52.8 years STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	35 Participants n=7 Participants	70 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment United States	51 participants n=5 Participants	49 participants n=7 Participants	100 participants n=5 Participants
Education	16.1 years STANDARD_DEVIATION 2. • n=5 Participants	16.3 years STANDARD_DEVIATION 3.2 • n=7 Participants	16.2 years STANDARD_DEVIATION 2.9 • n=5 Participants
Cognitive Function	29.5 points STANDARD_DEVIATION 0.8 • n=5 Participants	29.6 points STANDARD_DEVIATION 0.6 • n=7 Participants	29.5 points STANDARD_DEVIATION 0.7 • n=5 Participants
Apolipoprotein E4 carrier	21 participants n=5 Participants	17 participants n=7 Participants	38 participants n=5 Participants
Total cholesterol	192.8 mg/dL STANDARD_DEVIATION 36.4 • n=5 Participants	187.6 mg/dL STANDARD_DEVIATION 27.7 • n=7 Participants	190.3 mg/dL STANDARD_DEVIATION 32.4 • n=5 Participants
High-sensitivity c-reactive protein	2.59 mg/L STANDARD_DEVIATION 3.71 • n=5 Participants	2.03 mg/L STANDARD_DEVIATION 2.21 • n=7 Participants	2.32 mg/L STANDARD_DEVIATION 3.06 • n=5 Participants
Cerebrospinal fluid beta-amyloid-42	345.6 ng/L STANDARD_DEVIATION 77.1 • n=5 Participants	331.0 ng/L STANDARD_DEVIATION 83.7 • n=7 Participants	338.7 ng/L STANDARD_DEVIATION 80.2 • n=5 Participants

PRIMARY outcome

Timeframe: baseline and 9 months

Population: 1 participant declined follow up CSF collection in simvastatin arm; CSF could not be accessed at month 9 in 1 participant in placebo arm

Outcome measures

Outcome measures
Measure	Simvastatin n=48 Participants Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo n=45 Participants Matching placebo tablet nightly for 9 months
Change in Cerebrospinal Fluid (CSF) Beta-amyloid-42	-5.2 ng/L Standard Deviation 44.1	-3.1 ng/L Standard Deviation 38.2

SECONDARY outcome

Timeframe: baseline and 9 months

Population: Number of participants analyzed represent participants in MRI substudy with readable MRI scans at both baseline and 9 months; 24 and 17 readable MRI scans in simvastatin and placebo arms, respectively. Unusable MRI scans resulted from poor quality images due to technical problems.

Mean changes noted in posterior cingulate cortex

Outcome measures

Outcome measures
Measure	Simvastatin n=24 Participants Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo n=17 Participants Matching placebo tablet nightly for 9 months
Changes in Regional Cerebral Blood Flow on MRI	4.09 mL/100 g/min Standard Deviation 6.69	-5.08 mL/100 g/min Standard Deviation 8.28

SECONDARY outcome

Timeframe: baseline and 9 months

Population: 2 participants in the simvastatin arm and 3 participants in the placebo arm had incomplete hs-CRP results

Change noted in serum high-sensitivity c-reactive protein

Outcome measures

Outcome measures
Measure	Simvastatin n=47 Participants Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo n=43 Participants Matching placebo tablet nightly for 9 months
Change in Inflammatory Markers	-1.16 mg/L Standard Deviation 3.55	-0.31 mg/L Standard Deviation 1.83

SECONDARY outcome

Timeframe: Baseline and 9 months

Population: 1 participant in simvastatin arm with missing data

Change in Hopkins Verbal Learning Test Delayed Recall The Hopkins Verbal Learning Test Delayed Recall score is the raw number of words recalled at Trial 4, adjusted for years of education and age. This is a 12-item word list test.

Outcome measures

Outcome measures
Measure	Simvastatin n=48 Participants Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo n=46 Participants Matching placebo tablet nightly for 9 months
Changes in Cognitive Performance	0.40 adjusted words recalled Standard Deviation 1.38	0.26 adjusted words recalled Standard Deviation 1.54

Adverse Events

Simvastatin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Simvastatin n=51 participants at risk Simvastatin 40 mg tablet nightly for 1 month then 80 mg tablet nightly for 8 months	Placebo n=49 participants at risk Matching placebo tablet nightly for 9 months
Musculoskeletal and connective tissue disorders Elevated creatine kinase (CK) (> 2 times upper limit of normal)	2.0% 1/51 • Number of events 1 • 9 months	0.00% 0/49 • 9 months
Hepatobiliary disorders Elevated liver transaminases (>2 times upper limit of normal)	3.9% 2/51 • Number of events 2 • 9 months	0.00% 0/49 • 9 months
Psychiatric disorders Anxiety/depression	2.0% 1/51 • Number of events 1 • 9 months	0.00% 0/49 • 9 months
Gastrointestinal disorders Gastrointestinal discomfort	0.00% 0/51 • 9 months	2.0% 1/49 • Number of events 1 • 9 months

Additional Information

Cynthia M. Carlsson, MD, MS

University of Wisconsin School of Medicine and Public Health

Phone: 608-280-7000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place