ALA-enriched Nutrition for Prevention of Cognitive Decline in APOE4 Older Adults

NCT07392723 | Recruiting Phase 2 FDA Drug

• 1 other identifier: Pro2025000006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, placebo-controlled pilot trial will evaluate the effects of alpha-linolenic acid (ALA) supplementation on cognitive function, blood-brain barrier integrity, and brain vascular health in older adults with mild cognitive impairment and APOE4 genotype. By targeting the endogenous synthesis of docosahexaenoic acid (DHA) through ALA supplementation, the investigators aim to overcome the limitations of direct DHA supplementation, particularly in APOE4 carriers who exhibit low brain DHA levels and impaired blood-brain barrier function. This innovative approach offers a safe, cost-effective, and easily implementable therapeutic strategy for older adults at high risk for Alzheimer's dementia, especially APOE4 carriers, addressing a critical need given the limited cognitive benefits and significant adverse events of current amyloid-clearing drugs in this population.

Conditions

Alzheimer Disease; Blood-Brain Barrier; Apolipoprotein E, Deficiency or Defect of; Brain Aging; Fatty Acids, Omega-3; Cognitive Dysfunction

Keywords

Alpha-Linolenic Acid; Flaxseed Oil; Apolipoprotein E4; Nutritional Intervention; APOE4 Dysfunction; Cognitive Function; Brain MRI; Blood Biomarkers; Vascular Integrity; Neurodegeneration; Aging Brain; Memory Loss Prevention; AD Prevention Trial; Alzheimer's Disease; Cognitive decline prevention; Blood-brain barrier; Dementia prevention; Older adults; Biomarkers; Magnetic resonance imaging (MRI)

Outcome Measures

Primary Outcomes (3)

• Change in global cognitive (score) function

  Change in global cognition score from baseline to 6 months measured by an average of the z-scores across a broad cognitive battery, will be compared between ALA and placebo groups.

  Baseline and 6 months

• Change in Blood-Brain Barrier Integrity - Permeability of the BBB

  Blood-brain barrier (BBB) permeability will be assessed using the water exchange rate constant (Kw), derived from a validated motion-corrected diffusion-weighted pseudocontinuous arterial spin labeling (MCDW-pCASL) MRI sequence. Values will be extracted from whole-brain and region-specific areas, including hippocampus, dorsolateral frontal cortex, and parietal cortex. Changes from baseline to 6 months will be compared between ALA and placebo groups.

  Baseline and 6 months

• Levels of blood biomarkers of BBB Integrity

  Changes in protein levels in serum of: mfsd2a, s100B, and Glial Fibrillary Acidic Protein (GFAP) indicative of BBB function. Changes from baseline to 6 months will be compared between ALA and placebo groups.

  baseline and 6 months

Secondary Outcomes (7)

• Episodic Memory

  Baseline and 6 months

• Executive Function

  Baseline and 6 months

• Cerebral Blood Flow

  Baseline and 6 months

• Brain Vascular Reactivity

  Baseline and 6 months

• White Matter Hyperintensity (WMH)

  Baseline and 6 months

Study Arms (2)

ALA Group

EXPERIMENTAL

Participants receive flaxseed oil in 5 mL oral syringes containing 2.6g of ALA, taken daily for six months.

Drug: Alpha-Linolenic Acid (2.6 g/day)

Placebo Control Group

PLACEBO COMPARATOR

Participants receive corn oil without ALA (iso-caloric placebo) in 5 mL oral syringes that are identical in appearance to those containing ALA, taken daily for six months.

Dietary Supplement: Placebo Control Group

Interventions

Placebo Control Group DIETARY_SUPPLEMENT

Participants in this group will take corn oil that does not contain ALA. The oil will be provided in the same 5 mL prefilled oral syringes as the active supplement and will look, taste, and smell similar to the ALA oil. Participants will take one syringe daily in the morning with food for six months. The placebo is used to compare effects against the ALA supplement and to maintain blinding for both participants and study staff.

Also known as: Corn Oil, Placebo Control

Placebo Control Group

Alpha-Linolenic Acid (2.6 g/day) DRUG

Participants in this group will take flaxseed oil that contains 2.6 grams of alpha-linolenic acid (ALA) each day for six months. The oil will be provided in 5 mL prefilled oral syringes prepared by the Rutgers Clinical Research Pharmacy. Participants will take one syringe daily in the morning with food. They may mix the oil with cold foods such as yogurt or applesauce but should not heat it. The ALA supplement is intended to improve cognitive and brain health by enhancing the body's natural production of DHA that supports blood-brain barrier integrity and brain function.

Also known as: Flaxseed Oil, ALA

ALA Group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60 years or older
• Have amnestic Mild Cognitive Impairment (MCI) - memory problems that do not interfere with daily life.
• Carry at least one APOE4 gene allele (determined by a blood test).
• Be fluent in English or Spanish.
• Have a study partner (family member or friend) who can provide information about daily function.
• Have the ability to give informed consent and comply with study visits and procedures.

You may not qualify if:

• A diagnosis of dementia or any other brain disease that significantly affects thinking or memory (e.g., Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy, traumatic brain injury).
• History of stroke or other major neurological condition.
• Short life expectancy due to end-stage disease or other serious medical condition.
• Active cancer treatment that could interfere with study participation.
• Allergy or sensitivity to flaxseed oil or corn oil.
• Current use of flaxseed, flax oil, or fish oil supplements more than once per week.
• MRI contraindications, such as pacemakers, metallic implants, or severe claustrophobia.
• Current or past history of prostate cancer, regardless of remission status, OR a prostate-specific antigen (PSA) level \> 20 ng/mL at screening.
• Use of experimental Alzheimer's treatments (e.g., amyloid monoclonal antibodies) unless on a stable regimen as confirmed by the treating physician.

Sponsors & Collaborators

• Michal Schnaider Beeri, Ph.D.: lead

Study Sites (1)

Rutgers - Institute for Health

New Brunswick, New Jersey, 08901, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Apolipoprotein E, Deficiency or Defect of; Nerve Degeneration

Interventions

alpha-Linolenic Acid; Linseed Oil; Corn Oil

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Linolenic Acids; Fatty Acids, Essential; Fatty Acids, Unsaturated; Fatty Acids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Michal Beeri, PHD

  Rutgers University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudio Mendes, MS

CONTACT

8489328412; alastudy@njms.rutgers.edu

Rebecca West-Mortimer, PHD

CONTACT

8489328415; alastudy@njms.rutgers.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, study coordinators, and investigators conducting assessments will not know which oil each participant receives. Randomization and labeling are handled by the Rutgers Clinical Research Center Pharmacy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Krieger-Klein Endowed Chair in Neurodegeneration Research; Director of Herbert and Jacqueline Krieger Alzheimer's and Dementia Clinical Research and Treatment Center; and Professor of Neurology at Robert Wood Johnson Medical School

Model Details: Two groups: 1. Flaxseed oil (ALA 2.6 g/day) 2. Placebo (corn oil, iso-caloric control)

Study Record Dates

• First Submitted: October 20, 2025
• First Posted: February 6, 2026
• Study Start: January 12, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: February 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD will be made available after the main results of the study are published. This is anticipated to occur in June 2028.
• Access Criteria: Qualified researchers will be able to access de-identified individual participant data and supporting documents (such as the study protocol and statistical analysis plan) upon reasonable request. Access will be provided after publication of the main results, following approval by the study sponsor and completion of a data use agreement.

Locations

US (1)