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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04279743
• Other study ID #: IRSC-2020
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2020
• Est. completion date: April 1, 2025

Study information

• Verified date: May 2020
• Source: Université de Sherbrooke
• Contact: Melanie Plourde, PhD
• Phone: 819-780-2220
• Email: Melanie.Plourde2[@]USherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• omega-3 phospholipids
The intervention is a randomized double blind parallel design testing the metabolism of a krill oil omega-3 phospholipid supplement compared to fish oil omega-3 triglycerides in carriers and non-carriers of the ApoE4 allele. Half of the carriers and non-carriers will receive phospholipids and the other half will receive triglycerides. The intervention choice will be randomized and double blind. Participants will be instructed to take 4 supplements every day (2 in the morning and 2 in the evening) (4 g/ day of phospholipids), providing 1.8 g/day of omega-3 fatty acids. They will come back fasted to the research center on weeks 0, 1, 2, 3, 4, 8 and 12 of the study for blood draws. The omega-3 fatty acids metabolism will be compared between the carriers and non carriers of the ApoE4 allele.
• omega-3 Triglycerides
The intervention is a randomized double blind parallel design testing the metabolism of a krill oil omega-3 phospholipid supplement compared to fish oil omega-3 triglycerides in carriers and non-carriers of the ApoE4 allele. Half of the carriers and non-carriers will receive phospholipids and the other half will receive triglycerides. The intervention choice will be randomized and double blind. Participants will be instructed to take 4 supplements every day (2 in the morning and 2 in the evening), providing 1.8 g/day of omega-3 fatty acids. They will come back fasted to the research center on weeks 0, 1, 2, 3, 4, 8 and 12 of the study for blood draws. The omega-3 fatty acids metabolism will be compared between the carriers and non carriers of the ApoE4 allele.

Locations

Country	Name	City	State
Canada	Centre de Recherche sur le Vieillissement	Sherbrooke	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Université de Sherbrooke

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DHA levels in LPC and FFA	To evaluate plasma DHA levels in lysophosphatidylcholine and free fatty acids by ApoE genotype and treatment intervention.	baseline, 1, 2, 3, 4, 8 and 12 weeks after baseline
Primary	EPA levels in LPC and FFA	To evaluate plasma EPA levels in lysophosphatidylcholine and free fatty acids by ApoE genotype and treatment intervention.	baseline, 1, 2, 3, 4, 8 and 12 weeks after baseline