This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid (BRAVE-EPA)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by VA Office of Research and Development
Sponsor:
Collaborator:
University of Wisconsin, Madison
Information provided by (Responsible Party):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT02719327
First received: March 21, 2016
Last updated: July 14, 2017
Last verified: July 2017
  Purpose
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.

Condition Intervention Phase
Alzheimer's Disease Drug: icosapent ethyl (IPE) Other: gel cap placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults

Resource links provided by NLM:


Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:
  • Regional cerebral blood flow using arterial spin-labeling MRI [ Time Frame: 18 months ]
    Brain blood flow in a statistical region of interest will be measured through arterial spin-labeling MRI


Secondary Outcome Measures:
  • Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease [ Time Frame: 18 months ]
    CSF beta-amyloid, total tau, and phosphorylated tau

  • cognitive performance [ Time Frame: 18 months ]
    Preclinical Alzheimer's Cognitive Composite (PACC)


Estimated Enrollment: 150
Actual Study Start Date: December 1, 2016
Estimated Study Completion Date: November 30, 2021
Estimated Primary Completion Date: November 30, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: icosapent ethyl (IPE)
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Drug: icosapent ethyl (IPE)
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Other Name: Vascepa
Placebo Comparator: placebo
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Other: gel cap placebo
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Other Name: Placebo

Detailed Description:
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 with increased risk for developing AD due to parental history of the disease and increased prevalence of apolipoprotein E4 (APOE4) allele. 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.
  Eligibility

Ages Eligible for Study:   50 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Parental history of Alzheimer's disease
  • 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 cholesterol-lowering medication or fish oil supplements
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02719327

Contacts
Contact: Cynthia M Carlsson, MD MS Cynthia.Carlsson@va.gov
Contact: Elena G Beckman (608) 256-1901 Elena.Beckman@va.gov

Locations
United States, Wisconsin
William S. Middleton Memorial Veterans Hospital, Madison, WI Recruiting
Madison, Wisconsin, United States, 53705
Contact: Aaron F Heneghan, PhD    608-256-1901 ext 17801    Aaron.Heneghan@va.gov   
Contact: Nasia Safdar, MD PhD    (608) 280-7007    Nasia.Safdar@va.gov   
Principal Investigator: Cynthia M. Carlsson, MD MS         
Sponsors and Collaborators
VA Office of Research and Development
University of Wisconsin, Madison
Investigators
Principal Investigator: Cynthia M. Carlsson, MD MS William S. Middleton Memorial Veterans Hospital, Madison, WI
  More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02719327     History of Changes
Other Study ID Numbers: CLNA-001-15S
CX001261 ( Other Grant/Funding Number: VA Merit )
Study First Received: March 21, 2016
Last Updated: July 14, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:
Alzheimer's disease
Cerebrospinal fluid
brain blood flow
cognition
icosapent ethyl
Vascepa
omega-3 fatty acids
eicosapentaenoic acid

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Eicosapentaenoic acid ethyl ester
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on August 23, 2017