DHA Brain Delivery Trial (PreventE4)

The Delivery of Essential Fatty Acids to the Brain

Carrying the APOE ɛ4 allele is the strongest genetic risk factor for developing Alzheimer's disease. The goal of this project is to identify whether carrying the APOE ɛ4 allele is associated with reduced delivery of DHA to the brain. This information will help us identify the target population that could benefit from DHA supplementation to prevent cognitive decline.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain DHA Delivery and Alzheimer's Disease Risk
• Intervention / Treatment: Drug: DHA; Drug: Placebo

Detailed Description

The Brain DHA Delivery Trial will examine the effect of APOE genotype on the changes of cerebrospinal fluid (CSF) DHA to Arachidonic acid (AA) ratio in 184 cognitively healthy older individuals in response to DHA supplementation. Randomized clinical trials have yielded mixed results on the effect DHA supplementation on cognitive outcomes. This study asks the critical question of whether DHA gets into the brain in sufficient amounts after supplementation, and whether APOE genotype affects brain penetrance.

This trial will also test the effect of DHA supplementation on changes in brain structural and functional connectivity assessed by MRI, and changes in cognition after two years of supplementation in all 368 participants.

• Study Type: Interventional
• Enrollment (Anticipated): 368
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Keck School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: ≥ 55 and ≤ 80
• At least one dementia risk factor (obesity, education years, hypertension, hyperlipidemia)
• Mini-Mental State Examination (MMSE) ≥ 25
• Logical Memory II delayed recall score ≥ 6 and ≤ 18 .

Exclusion Criteria:

• Diagnosis of dementia as assessed by the investigator
• Use of omega-3 preparations in the last 3 months
• > 200 mg/day of DHA consumption using a validated questionnaire
• Use of donepezil, rivastigmine, galantamine and/or memantine
• Alcohol or drug abuse
• A concomitant serious disease such as active cancer treatment or HIV.
• Participation in a clinical trial in the last 30 days
• Use of anticoagulants such as Plavix or Coumadin or the newer generation blood thinners.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DHA; oral DHA supplementation at 2 grams per day	Drug: DHA; DHA supplementation
Placebo Comparator: Placebo; Placebo for DHA	Drug: Placebo; Placebo for DHA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in cerebrospinal fluid fatty acid levels after the intervention in 184 subjects	cerebrospinal fluid fatty acids assessed by mass spectrometry	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in functional connectivity using resting state functional MRI in all 368 participants	Functional Connectivity	2 years
Change in structural connectivity using MRI in all 368 participants	Structural connectivity	2 years
Change in cognitive measures using the Neuropsychological Outcomes (RBANS) in all 368 participants	RBANS battery	2 years

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Institute on Aging (NIA); Alzheimer's Drug Discovery Foundation; Huntington Medical Research Institutes
• Investigators: Principal Investigator: Hussein Yassine, MD, University of Southern California

Publications and helpful links

General Publications

• Yassine HN, Braskie MN, Mack WJ, Castor KJ, Fonteh AN, Schneider LS, Harrington MG, Chui HC. Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E epsilon4 Carriers: A Review. JAMA Neurol. 2017 Mar 1;74(3):339-347. doi: 10.1001/jamaneurol.2016.4899.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Apolipoprotein E4; Docosahexaenoic Acids
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: HS-18-00291/00984; R01AG054434 (U.S. NIH Grant/Contract); GC-201711-2014197 (Other Grant/Funding Number: Alzheimer's Drug Discovery Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: available by request to study principal investigator and after approval by study committee.
• IPD Sharing Time Frame: within 1 year after study publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No