Trial Outcomes & Findings for Effects of Simvastatin on Biomarkers (NCT NCT01142336)

NCT ID: NCT01142336

Last Updated: 2017-07-28

Results Overview

CSF Aβ42 concentration were measured at baseline and after 1-year intervention.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

49 participants

Primary outcome timeframe

1-year change of CSF Aβ42 from baseline

Results posted on

2017-07-28

Participant Flow

Statin-naïve middle-aged adults were recruited for this single-site trial (Seattle, WA) from the University of Washington Alzheimer's Disease Research Center Registry or the community through newsletters, websites, educational talks, health fairs, local clinics, and newspaper and magazine advertisements.

917 people were pre-screened by phone for eligibility, 400 did not respond or declined, 457 did not meet inclusion/exclusion criteria. 60 completed a full screen visit. Of these 60 potential participants, 2 were lost to follow-up after screen, 2 withdrew, 7 screen failed and 49 were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Simvastatin Simvastatin 40mg qHS for 1 year	Placebo Placebo 1 tablet qHS for 1 year
Overall Study STARTED	26	23
Overall Study COMPLETED	25	21
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Simvastatin Simvastatin 40mg qHS for 1 year	Placebo Placebo 1 tablet qHS for 1 year
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Effects of Simvastatin on Biomarkers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=23 Participants Placebo 1 tablet qHS for 1 year	Simvastatin n=26 Participants Simvastatin 40mg qHS for 1 year	Total n=49 Participants Total of all reporting groups
Age, Continuous	56.1 years STANDARD_DEVIATION 4.9 • n=5 Participants	55.7 years STANDARD_DEVIATION 4.5 • n=7 Participants	55.9 years STANDARD_DEVIATION 4.7 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	26 participants n=7 Participants	49 participants n=5 Participants
CSF Aβ42 level	515 pg/ml STANDARD_DEVIATION 113 • n=5 Participants	520 pg/ml STANDARD_DEVIATION 114 • n=7 Participants	517 pg/ml STANDARD_DEVIATION 113 • n=5 Participants
CSF total tau level	43 pg/ml STANDARD_DEVIATION 17 • n=5 Participants	38 pg/ml STANDARD_DEVIATION 16 • n=7 Participants	41 pg/ml STANDARD_DEVIATION 16 • n=5 Participants
CSF ptau level	31 pg/ml STANDARD_DEVIATION 15 • n=5 Participants	27 pg/ml STANDARD_DEVIATION 10 • n=7 Participants	29 pg/ml STANDARD_DEVIATION 12 • n=5 Participants

PRIMARY outcome

Timeframe: 1-year change of CSF Aβ42 from baseline

Population: In the Placebo group, 1 participant was dropped due to AE and 1 was lost to follow-up. In the Simvastatin group, 1 participant was dropped due to AE. These 3 participants were not included in the primary analysis per analysis plan. All these 3 subjects were not included in the primary analysis based on our per protocol analysis plan.

CSF Aβ42 concentration were measured at baseline and after 1-year intervention.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants 1 tab qHS for 1 year	Simvastatin n=25 Participants 40mg qHS for 1 year
Change From Baseline in Aβ42 in Cerebrospinal Fluid (CSF) at 1 Year	5.3 1-yr change, pg/ml Standard Deviation 31	0.5 1-yr change, pg/ml Standard Deviation 42

PRIMARY outcome

Timeframe: 1-yr change

CSF total tau was measured at baseline and after 1-year of intervention

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants 1 tab qHS for 1 year	Simvastatin n=25 Participants 40mg qHS for 1 year
Change From Baseline in CSF Total Tau at 1 Year	-0.1 pg/ml Standard Deviation 3.9	1.6 pg/ml Standard Deviation 4.7

PRIMARY outcome

Timeframe: 1-year change from baseline

ptau 181 measured in CSF at baseline and after 1-year intervention

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants 1 tab qHS for 1 year	Simvastatin n=25 Participants 40mg qHS for 1 year
Change From Baseline in CSF ptau181 at 1 Year	-2.9 1-yr change (final - baseline), pg/ml Standard Deviation 12.9	1.7 1-yr change (final - baseline), pg/ml Standard Deviation 6.3

Adverse Events

Simvastatin

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Ge Li, MD, PhD

University of Washington

Phone: (206) 764-2485

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Simvastatin n=26 participants at risk Simvastatin 40mg qHS for 1 year	Placebo n=23 participants at risk Placebo 1 tablet qHS for 1 year
General disorders Headache	26.9% 7/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	34.8% 8/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Gastrointestinal disorders Nausea	11.5% 3/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	8.7% 2/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Gastrointestinal disorders Diarrhea	19.2% 5/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	8.7% 2/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Gastrointestinal disorders Constipation	11.5% 3/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	8.7% 2/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	53.8% 14/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	39.1% 9/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Psychiatric disorders Memory Problems	3.8% 1/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	21.7% 5/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Psychiatric disorders Depressed Mood	7.7% 2/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	17.4% 4/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Psychiatric disorders Anxiety	11.5% 3/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	34.8% 8/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
General disorders Insomnia	26.9% 7/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	21.7% 5/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Musculoskeletal and connective tissue disorders Muscle Pain	23.1% 6/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	34.8% 8/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Musculoskeletal and connective tissue disorders Muscle Weakness	7.7% 2/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	4.3% 1/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Metabolism and nutrition disorders Elevated Blood Glucose	11.5% 3/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	21.7% 5/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Hepatobiliary disorders Elevated serum glutamic-oxaloacetic transaminase (SGOT)	11.5% 3/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	21.7% 5/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Hepatobiliary disorders Elevated Serum glutamic pyruvic transaminase (SGPT)	23.1% 6/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	4.3% 1/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.
Musculoskeletal and connective tissue disorders Elevated serum creatine phosphokinase (CPK)	26.9% 7/26 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.	26.1% 6/23 • 1 year Adverse event information was collected systematically at phone and in-person safety visits spaced 6 weeks to 3 months apart for the duration of the 1 year study.