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

Primary Purpose

Alzheimer's Disease

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
icosapent ethyl (IPE)
gel cap placebo
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Alzheimer's Disease focused on measuring Alzheimer's disease, Cerebrospinal fluid, brain blood flow, cognition, icosapent ethyl, Vascepa, omega-3 fatty acids, eicosapentaenoic acid

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • William S. Middleton Memorial Veterans Hospital, Madison, WI

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

icosapent ethyl (IPE)

placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Regional cerebral blood flow using arterial spin-labeling MRI
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
CSF beta-amyloid, total tau, and phosphorylated tau
cognitive performance
Preclinical Alzheimer's Cognitive Composite (PACC)

Full Information

First Posted
March 21, 2016
Last Updated
October 6, 2022
Sponsor
VA Office of Research and Development
Collaborators
University of Wisconsin, Madison
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1. Study Identification

Unique Protocol Identification Number
NCT02719327
Brief Title
Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid
Acronym
BRAVE-EPA
Official Title
Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 8, 2017 (Actual)
Primary Completion Date
September 29, 2023 (Anticipated)
Study Completion Date
September 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
University of Wisconsin, Madison

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's disease, Cerebrospinal fluid, brain blood flow, cognition, icosapent ethyl, Vascepa, omega-3 fatty acids, eicosapentaenoic acid

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
1:1 randomization of icosapent ethyl 4 g daily vs matching placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
131 (Actual)

8. Arms, Groups, and Interventions

Arm Title
icosapent ethyl (IPE)
Arm Type
Experimental
Arm Description
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Intervention Type
Drug
Intervention Name(s)
icosapent ethyl (IPE)
Other Intervention Name(s)
Vascepa
Intervention Description
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Intervention Type
Other
Intervention Name(s)
gel cap placebo
Other Intervention Name(s)
Placebo
Intervention Description
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Primary Outcome Measure Information:
Title
Regional cerebral blood flow using arterial spin-labeling MRI
Description
Brain blood flow in a statistical region of interest will be measured through arterial spin-labeling MRI
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease
Description
CSF beta-amyloid, total tau, and phosphorylated tau
Time Frame
18 months
Title
cognitive performance
Description
Preclinical Alzheimer's Cognitive Composite (PACC)
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia M. Carlsson, MD MS
Organizational Affiliation
William S. Middleton Memorial Veterans Hospital, Madison, WI
Official's Role
Principal Investigator
Facility Information:
Facility Name
William S. Middleton Memorial Veterans Hospital, Madison, WI
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid

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