Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid

NCT02719327 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLNA-001-15SCX001261
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; Cerebrospinal fluid; brain blood flow; cognition; icosapent ethyl; Vascepa; omega-3 fatty acids; eicosapentaenoic acid

Outcome Measures

Primary Outcomes (1)

• Regional Cerebral Blood Flow Using Arterial Spin-labeling MRI

  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.

  18 month study visit

Secondary Outcomes (2)

• Cerebrospinal Fluid (CSF) Biomarkers of Alzheimer's Disease

  18 month study visit

• Cognitive Performance

  18 month study visit

Study Arms (2)

icosapent ethyl (IPE)

EXPERIMENTAL

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)

placebo

PLACEBO COMPARATOR

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

Interventions

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

Also known as: Vascepa

icosapent ethyl (IPE)

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

Also known as: Placebo

placebo

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Wisconsin, Madison: collaborator

Study Sites (1)

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

eicosapentaenoic acid ethyl ester

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Study sample lacked racial, ethnic and gender diversity. The study was on-going during COVID-19 closures which impacted participants' ability to take part in in-person study procedures.

Results Point of Contact

• Title: Cynthia Carlsson, MD, MS; Professor of Medicine (Geriatrics)
• Organization: Madison Veterans Affairs Geriatrics Research, Education & Clinical Center (GRECC)

cynthia.carlsson@va.gov

608-280-7000

Study Officials

• Cynthia M. Carlsson, MD MS

  William S. Middleton Memorial Veterans Hospital, Madison, WI

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 1:1 randomization of icosapent ethyl 4 g daily vs matching placebo

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: March 25, 2016
• Study Start: June 8, 2017
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)