Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Determining the Blood-to-brain Link

Université de Sherbrooke

Status: Not yet enrolling

Conditions: Healthy

Treatments: Dietary Supplement: omega-3 phospholipids; Dietary Supplement: omega-3 Triglycerides

Study type: Interventional

Funder types: Other

Identifiers

NCT04279743

IRSC-2020

Details and patient eligibility

About

In Canada, ~17 millions of adults between 30-64 y old could benefit from a prevention strategy to lower the risk of Alzheimer's disease (AD). Although a lot of epidemiological studies reported positive cognitive outcomes in populations eating fish, there is skepticism about the link between docosahexaenoic acid (DHA), an omega-3 (OM3) fatty acid in fish and prevention of cognitive decline. This is largely because there is a disconnect between epidemiological, molecular and animal studies which generally favor a link between higher DHA intake and cognition whereas clinical DHA and fish oil trial seem not to support such as link. There are several knowledge gaps in this field that might explain why clinical trials were not successful. This project will focus on two major gaps : OM3 fatty acid metabolism and the blood-to-brain DHA link. OM3 supplements in cardiovascular disease have faced the same issues for decades but the more recent trials have now generated the clinical evidence supporting primary and secondary cardiovascular events reduction and a better risk to benefit balance of OM3 drugs compared to statins, for instance. What if, for cognitive decline, the target was missed because the supplement/drug formulations were not appropriately designed to target the brain? The investigators hypothesize that (i) E4 carriers display a faulty packaging of circulating OM3, leading to reduced bioavailability for brain cells, (ii) The use of new OM3 formulation can direct plasma DHA into brain compartments more readily available for the brain, thereby increasing brain DHA concentrations and improving cognition. Studies in mice and humans will be performed to test OM3 metabolism and the blood-to-brain DHA link. Ultimately the information generated in this research project will help to better design clinical trials in term of fatty acid formulation, expected level to reach in the plasma and the brain.

Enrollment: 160 estimated patients

Sex: All

Ages: 30 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Men and women aged between 30-50 years old.

Exclusion criteria

• Tobacco use,
• Malnutrition (assessed from blood albumin, hemoglobin and lipids),
• Diabetes,
• Participants taking an EPA+DHA supplement or consuming more than 2 fish meals per week,
• Uncontrolled thyroid, renal and endocrine disorder disease,
• Chronic immune condition or inflammation (CRP > 10 mg/l, white cell count),
• Cancer,
• Recent major surgery or cardiac event,
• Pregnant or lactating women,
• Pre-menopause or menopause,
• Dementia,
• Ongoing or past severe drug or alcohol abuse,
• Psychiatric difficulties or major depression
• Ongoing or past intensive physical training.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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160 participants in 2 patient groups

ApoE4 carriers

Experimental group

Description:

The results obtained for APOE4 carriers will be compared to the one obtained from APOE4 non-carriers. Carriers are defined as being at least carrier of one APOE4 allele.

Treatment:

Dietary Supplement: omega-3 Triglycerides

Dietary Supplement: omega-3 phospholipids

ApoE4 non carriers

Experimental group

Description:

The results obtained for APOE4 carriers will be compared to the one obtained from APOE4 non-carriers. Carriers are defined as being at least carrier of one APOE4 allele.

Treatment:

Dietary Supplement: omega-3 Triglycerides

Dietary Supplement: omega-3 phospholipids