Clinical trial NCT04279743: Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Determining the Blood-to-brain Link
Official title: Fatty Acid Metabolism in Carriers of Apolipoprotein E Epsilon 4 Allele: Determining the Blood-to-brain Link
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Healthy
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
First posted: 2020-02-21
Enrollment: 160
Sex: ALL
Minimum age (years): 30
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind controlled randomized study with a parallel study design (40 men and 40 women, ApoE4 carriers and non carriers)
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: DHA levels in LPC and FFA
timeFrame: baseline, 1, 2, 3, 4, 8 and 12 weeks after baseline
measure: EPA levels in LPC and FFA
timeFrame: baseline, 1, 2, 3, 4, 8 and 12 weeks after baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre de Recherche sur le Vieillissement
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Melanie Plourde, PhD
role: PRINCIPAL_INVESTIGATOR
References: