Effects of Simvastatin on Biomarkers

NCT01142336 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 3737300183
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

A year-long randomized, double-blind, placebo-controlled trial of simvastatin to see if it produces beneficial changes in cerebral spinal fluid proteins associated with Alzheimer's disease.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease; Prevention; Spinal Fluid; Biomarkers; Simvastatin

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Aβ42 in Cerebrospinal Fluid (CSF) at 1 Year

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

  1-year change of CSF Aβ42 from baseline

• Change From Baseline in CSF Total Tau at 1 Year

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

  1-yr change

• Change From Baseline in CSF ptau181 at 1 Year

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

  1-year change from baseline

Study Arms (2)

Simvastatin

EXPERIMENTAL

Simvastatin 40mg qHS for 1 year

Drug: Simvastatin

Placebo

PLACEBO COMPARATOR

Placebo 1 tablet qHS for 1 year

Drug: Placebo

Interventions

Simvastatin DRUG

Simvastatin 40mg qHS for 1 year

Also known as: Zocor

Simvastatin

Placebo DRUG

Placebo 1 tablet qHS for 1 year

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 45 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• If female of childbearing potential, must have negative pregnancy test at baseline, and all subsequent visits.
• Age 45 to 64 years inclusive.
• Considered cognitively normal with no evidence of memory or other cognitive impairments (MMSE \>26, Logical Memory delayed recall \> 6, CDR score of 0).
• Normal or only mildly elevated cholesterol which does not require drug therapy based on National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP-III) guidelines.
• An LDL level above 70mg/dL.
• Hamilton Depression Scale (HAM-D) score \< 12.
• BMI between 18 - 34 (or exception made by MD).
• In good recent general health (i.e., no trauma or infection in the 4 weeks before LP).
• Platelet count \>100,000.

You may not qualify if:

• Any contraindications to LP, such as spinal deformity, severe disease or infection in the LP region, bleeding tendency, anticoagulant or blood-thinning medications.
• Taken a statin medication in the past 12 months.
• Any clinically significant laboratory abnormalities.
• Any neurological disorders: multiple sclerosis, epilepsy, stroke, Parkinson's, other degenerative CNS disorders, or neuropathy with radicular involvement.
• Acute or chronic major psychiatric disorders: schizophrenia, affective disorders, or severe anxiety disorders. (Dysthymia allowed, history of MDD allowed if currently in remission)
• Unstable or poorly controlled medical problems such as: heart failure, diabetes (poorly controlled or insulin dependent), hypertension (BP \>160/100), pulmonary disease with hypoxia or hypercapnia, significant liver disease or known hepatitis C seropositivity, renal failure, treatment for cancer in the past 2 years (other than non-melanoma skin cancer) or known HIV positive status.
• Use of illegal drugs or alcohol abuse (\>2 drinks/day or 10/week) within the past year.
• Concurrent participation in another investigational drug study.
• Drugs which could interact with statins: itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, amiodarone, cyclosporine, isoniazid, quinidine, or large quantities of grapefruit juice (\>1 quart daily)
• Central nervous system acting medications: antipsychotics, anti-Parkinson's disease medications, anti convulsants, or CNS stimulants
• Chronic use of benzodiazepines, sedating antihistamines, or other sedative-hypnotic agents (prn use is allowed as long as it is not within 72 hours of LP or cognitive testing)
• Medications affecting coagulation and/or inflammation: coumadin, potent anti-inflammatory medications (hydrocortisone, methotrexate or other potent immune-modulating medications), and anti-HIV medications (Aspirin up to 325 mg/day is allowed.)
• Lipid-lowering drugs: fibrates or niacin \>500mg/day (stable dose of omega-3 is allowed)
• Does the subject's family history meet any of the following criteria?
• Both parents had/have dementia

Sponsors & Collaborators

• University of Washington: lead
• Seattle Institute for Biomedical and Clinical Research: collaborator
• VA Puget Sound Health Care System: collaborator

Study Sites (1)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Simvastatin; Sugars

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

Sample size is small and statistical power is limited.

Results Point of Contact

• Title: Ge Li, MD, PhD
• Organization: University of Washington

gli@uw.edu

(206) 764-2485

Study Officials

• Gail Li, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: June 9, 2010
• First Posted: June 11, 2010
• Study Start: June 1, 2010
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 28, 2017
• Results First Posted: July 28, 2017

Record last verified: 2017-06

Locations

US (1)