Clinical trial NCT03613844: DHA Brain Delivery Trial
Official title: The Delivery of Essential Fatty Acids to the Brain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain DHA Delivery and Alzheimer's Disease Risk
Keywords: Alzheimer's disease
Docosahexaenoic Acids
Apolipoprotein E4
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Huntington Medical Research Institutes
name: National Institute on Aging (NIA)
name: Alzheimer's Drug Discovery Foundation
First posted: 2018-08-03
Enrollment: 365
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind and randomized placebo controlled
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: change in cerebrospinal fluid fatty acid levels after the intervention in 184 subjects
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
measure: Change in functional connectivity using resting state functional MRI in all 368 participants
timeFrame: 2 years
measure: Change in structural connectivity using MRI in all 368 participants
timeFrame: 2 years
measure: Change in cognitive measures using the Neuropsychological Outcomes (RBANS) in all 368 participants
timeFrame: 2 years
Locations:
city: Los Angeles
country: United States
facility: USC Keck School of Medicine
state: California
Study officials:
affiliation: University of Southern California
name: Hussein Yassine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.