DHA Brain Delivery Trial (PreventE4)

• ClinicalTrials.gov Identifier: NCT03613844
• Recruitment Status: Active, not recruiting
• First Posted: August 3, 2018
• Last Update Posted: November 14, 2022
• Sponsor: University of Southern California
• Collaborators: Huntington Medical Research Institutes; National Institute on Aging (NIA); Alzheimer's Drug Discovery Foundation
• Information provided by (Responsible Party): Hussein Yassine, University of Southern California

Tracking Information

• First Submitted Date: July 11, 2018
• First Posted Date: August 3, 2018
• Last Update Posted Date: November 14, 2022
• Actual Study Start Date: July 1, 2018
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2022)

change in cerebrospinal fluid fatty acid levels after the intervention in 184 subjects [ Time Frame: 6 months ]

cerebrospinal fluid fatty acids assessed by mass spectrometry

Original Primary Outcome Measures (submitted: July 27, 2018)

change in cerebrospinal fluid fatty acid levels after the intervention [ Time Frame: 6 months ]

cerebrospinal fluid fatty acids assessed by mass spectrometry

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: June 2, 2022)

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

Original Other Pre-specified Outcome Measures (submitted: July 27, 2018)

• Brain MRI [ Time Frame: 2 years ]
  Functional Connectivity
• Brain MRI [ Time Frame: 2 years ]
  Structural connectivity
• Congition [ Time Frame: 2 years ]
  RBANS battery
• Cognition [ Time Frame: 2 years ]
  Cogtrack battery

Descriptive Information

• Brief Title: DHA Brain Delivery Trial
• Official Title: The Delivery of Essential Fatty Acids to the Brain
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

double blind and randomized placebo controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other

• Condition: Brain DHA Delivery and Alzheimer's Disease Risk

Intervention

• Drug: DHA
  DHA supplementation
• Drug: Placebo
  Placebo for DHA

Study Arms

• Experimental: DHA
  oral DHA supplementation at 2 grams per day
  Intervention: Drug: DHA
• Placebo Comparator: Placebo
  Placebo for DHA
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 10, 2022): 368
• Original Estimated Enrollment (submitted: July 27, 2018): 160
• Estimated Study Completion Date: May 1, 2025
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03613844
• 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: available by request to study principal investigator and after approval by study committee.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: within 1 year after study publication

• Current Responsible Party: Hussein Yassine, University of Southern California
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Southern California
• Original Study Sponsor: Same as current

Collaborators

• Huntington Medical Research Institutes
• National Institute on Aging (NIA)
• Alzheimer's Drug Discovery Foundation

Investigators

• Principal Investigator: Hussein Yassine, MD; University of Southern California

• PRS Account: University of Southern California
• Verification Date: November 2022