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Completed

NCT Number: NCT02719327

Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid

The number of Americans diagnosed with Alzheimer's disease (AD) is expected to triple by 2050. Compared to the general population, Veterans have a greater risk of AD, likely in part due to their increased incidence of traumatic brain injury, post-traumatic stress disorder, depression, and other vascular-related health issues. Based on available data, 423,000 new cases of AD are anticipated in Veterans by 2020. Thus, the discovery of effective therapies to prevent or delay the onset of AD in Veterans is critical. The goal of this study is to evaluate the efficacy of a purified form of the omega-3 fatty acid eicosapentaenoic acid (EPA) called icosapent ethyl (IPE), on improving brain blood flow, spinal fluid markers of AD pathology, and cognitive performance in middle-aged, cognitively-healthy Veterans with increased risk of AD. If IPE delays the onset of AD by even 5 years, the incidence of AD would be reduced by 50% in this population and could have a profound effect on Veteran quality of life and healthcare costs.

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Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

About this study

The proposed study is a proof-of-concept, randomized, placebo-controlled, double-blind, parallel-group clinical trial assessing the efficacy of 18 months of icosapent ethyl (IPE) therapy on magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and cognitive biomarkers for AD in 150 cognitively-healthy Veterans ages 50-75 years. The overarching goal of this trial is to assess whether icosapent ethyl beneficially affects intermediate physiological measures associated with onset of AD in order to evaluate whether larger, multi-site, longer-duration Alzheimer's prevention trials are warranted to assess more definitive clinical outcomes. The proposed study aims to: 1) investigate the effects of 18 months of IPE vs. placebo on regional cerebral blood flow as measured by arterial spin-labeling MRI; 2) determine the impact of 18 months of IPE vs. placebo on CSF biomarkers of AD pathology; and 3) evaluate the effects of 18 months of IPE vs. placebo on cognitive performance.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • United States Veteran eligible for VA care
  • Age 50-75 years, inclusive
  • Cognitively healthy

Exclusion criteria

  • Dementia or mild cognitive impairment on screening evaluation
  • Current use of fish oil supplements (requires 3 month wash-out period)
  • Active liver disease with AST or ALT greater than twice the upper limit of normal
  • Elevated creatine kinase greater than twice the upper limit of normal
  • Prior adverse reaction to statins or fish oil
  • Pregnant, nursing, or pregnancy planned
  • Use of medications that interact with icosapent ethyl
  • Current use of anticoagulants
  • Known hypersensitivity to fish and/or shellfish
  • Current use of other investigational drug
  • History of significant atherosclerotic cardiovascular disease or diabetes mellitus
  • Low-density lipoprotein (LDL) cholesterol > or =190 mg/dL or <80 mg/dL
  • Triglycerides > or = 500 mg/dL
  • Creatinine >1.8 mg/dL
  • Previous lumbar surgery with contraindication to lumbar puncture
  • Claustrophobia requiring sedation for MRI
  • Pacemaker or other contraindication for MRI
  • Consumption of >200 mg per day omega-3 fatty acids in diet

Treatment and study plan

icosapent ethyl (IPE)

Drug

Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo

Other names: Vascepa

gel cap placebo

Other

Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo

Other names: Placebo

Primary outcomes

  1. Regional Cerebral Blood Flow Using Arterial Spin-labeling MRI

    Time frame: 18 month study visit

    For the primary outcome we chose an anatomical region, posterior cingulate gyrus, that aligned with statistical region of interest sensitive to changes in cerebral blood flow in cognitively-unimpaired adults at risk for Alzheimer's disease. Brain blood flow was averaged across the right and left posterior cingulate gyrus.

Secondary outcomes

  1. Cerebrospinal Fluid (CSF) Biomarkers of Alzheimer's Disease

    Time frame: 18 month study visit

    CSF beta-amyloid-42, total tau, and phosphorylated tau-181 (Roche Cobas Elecsys e611). Lower CSF beta-amyloid-42 and higher phosphorylated tau-181 or total tau are associated with risk for Alzheimer's disease.

  2. Cognitive Performance

    Time frame: 18 month study visit

    Alzheimer's Disease Cooperative Study Preclinical Alzheimer's Cognitive Composite (ADCS-PACC). Composite scores at each time point are standardize to baseline values such that at baseline the mean=0 and the standard deviation = 1. Standardized scores range from -3.15 to 3.09. Higher scores indicate better cognition.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Collaborators

  • University of Wisconsin, Madison

Registry information

Official study title

Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults

Acronym: BRAVE-EPA

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Mar 25, 2016
Registry last updated
Nov 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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