NCT07392723 · Michal Schnaider Beeri, Ph.D.
ALA-enriched Nutrition for Prevention of Cognitive Decline in APOE4 Older Adults
What this study is about
This randomly assigned, where neither patients nor doctors know which treatment is given, compared against an inactive treatment 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.
View original scientific description
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.
Interventions
DRUG
Alpha-Linolenic Acid (2.6 g/day)
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.
DIETARY_SUPPLEMENT
Placebo Control Group
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.
Primary outcome measures
Change in global cognitive (score) function
Time frame: Baseline and 6 months
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.
Change in Blood-Brain Barrier Integrity - Permeability of the BBB
Time frame: Baseline and 6 months
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.
Levels of blood biomarkers of BBB Integrity
Time frame: baseline and 6 months
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Where
- New Brunswick, New Jersey
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Feb 6, 2026 · Source of record for eligibility and locations