Causal Relationships Between LC-omega-3-enriched Diet and Cognition (MOP201109)

May 6, 2020 updated by: Mélanie Plourde, Université de Sherbrooke
Nutrition is key to healthy aging for a number of diseases but the investigators have reported imbalances in the distribution of long chain omega-3 fatty acids (LC-omega-3) in the elderly and in the carriers of apolipoprotein E epsilon 4 (APOE4) isoform. Carrying APOE4 isoform is currently recognized as being the most important genetic risk factor of cognitive decline. The investigators believe that dysregulation of LC-omega-3 metabolism is intimately link with higher risk of cognitive decline. The current project will investigate whether there is a causal relationship between LC-omega-3-enriched diet and cognition using, on the one hand, a randomized double-blind placebo-controlled design and on the other hand, transgenic mice carrying human APOE4. In both study, the investigators will focus specifically on the distribution (level) of LC-omega-3 into lipoproteins with age and/or APOE4 isoform to evaluate whether dysfunctional transport of LC-omega-3 is associated with lower cognitive scores on visuospatial capacity, verbal fluency or working memory. In APOE4 mice, the investigators will evaluate LC-omega-3 brain uptake together with the level of LC-omega-3 in the brain membranes and the level of APOE protein within the brain. The present investigation will provide key basis for understanding how to develop nutritional strategies for healthy aging and the preservation of cognitive function.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OVERALL AIM: In human and animal models, to investigate imbalances in the distribution of long chain omega-3 fatty acids (LC-omega-3) in plasma lipids and lipoproteins brought about by age and APOE4 genotype and to evaluate whether these imbalances are linked with cognitive functions. BACKGROUND: Risk of cognitive decline increases with age. Epidemiological studies strongly support a link between lower risk of cognitive decline and higher intake of fatty fish containing LC-omega-3. However, our clinical studies show that there are imbalances in the distribution of LC-omega-3 in plasma lipids that occur during aging and in the carriers of apolipoprotein E epsilon4 (APOE4) genotype, the most important genetic risk for cognitive decline. As a consequence, these imbalances appear to contribute to dysregulation of LC-omega-3 metabolism and to higher risk of cognitive decline. Our preliminary results in elderly humans show that visuospatial, verbal fluency and working memory scores are improved after 4 months supplementation with 3 g/d LC-omega-3, supporting a beneficial role of LC-omega-3 in cognition in the elderly. How this beneficial effect occurs is unknown but is potentially because the supplementation reverses or overrides imbalances in brain LC-omega-3 uptake and tissue content occurring during aging and in APOE4 carriers. Molecular mechanisms will be evaluated in 4-month and 15-month old transgenic mice expressing human APOE4. OVERALL HYPOTHESIS: Higher LC-omega-3 levels in lipoproteins are associated with higher LC-omega-3 brain uptake and membrane levels in APOE4 carriers leading to better cognitive scores on visuospatial, verbal fluency and working memory tests.

RESEARCH PLAN: Specific questions to be addressed are:

1) What is the role of APOE4 and blood lipoproteins on the causal relationship between a LC-omega-3-enriched diet and cognition? Three hundred participants aged between 20-80 y old will be recruited and randomized into a placebo (corn oil) or 3 g/d omega-3 fatty acid supplement for 6 months (150 subjects/group). LC-omega-3 use mostly VLDL and LDL to travel in the blood. Hence, we will collect blood samples once monthly for quantification of LC-omega-3 levels into VLDL, LDL and HDL, with longitudinal follow-up of LC-omega-3 throughout the supplementation period. This will provide key information regarding differences lipoprotein content of LC-omega-3 over the supplementation. We will perform cognitive tests with a focus on visuospatial, verbal fluency and working memory in the placebo and in the LC-omega-3 treated groups before and after the supplement. Age, sex and APOE4 genotype will be the interaction variables of interest. Statistical association test between cognitive scores and LC-omega-3 distribution in lipoproteins will also be performed to find the best LC-omega-3 marker associated with cognition.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
273

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H4C4
        • PL Léveillé

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • male and female subjects aged between 20-80 years old

Exclusion Criteria:

  • tobacco use,
  • malnutrition (assessed from blood albumin, hemoglobin and lipids),
  • subjects taking an EPA+DHA supplement for more than one month,
  • swallowing problems,
  • severe gastro-intestinal problems,
  • diabetes,
  • uncontrolled thyroid disease,
  • severe renal failure,
  • liver disease or any other endocrine disorder,
  • medication that would affect lipoprotein metabolism,
  • chronic immune condition or inflammation (CRP > 10 mg/l, white cell count),
  • cancer,
  • recent major surgery or cardiac event,
  • pregnant or lactating women,
  • uncorrected visual or hearing problems,
  • dementia,
  • ongoing or past severe drug or alcohol abuse,
  • psychiatric difficulties or depression, and
  • ongoing or past intensive physical training

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Omega-3 fatty acid supplement
This study will use a randomized placebo-controlled double-blind design and the intervention period will be 6 months. Participants will be instructed to consume 4 x 1285 mg fish oil capsules/d, two capsules with eachthe breackfast and two capsules with dinner. The daily treatment will provide 1.4 g/d of DHA and 1.8 g/d of EPA (Ocean Nutrition Canada, Dartmouth, NS). All capsules will contain orange flavor to mask the fishy taste and odor of the LC-omega-3 oil and will be provided to the participants monthly.
Dietary supplement: omega-3 fatty acid supplementation
This study will use a randomized placebo-controlled double-blind design and the intervention period will be 6 months. Participants will be instructed to consume 4 x 1285 mg fish oil capsules/d, two capsules with each of the main daily meals. The placebo will be composed of corn/soybean oil as used in other randomized placebo-controlled trials. The daily treatment will provide 1.2 g/d of DHA and 2.4 g/d of EPA (Ocean Nutrition Canada, Dartmouth, NS). All capsules will contain citrus flavor to mask the fishy taste and odor of the LC-omega-3 oil and will be provided to the participants monthly.
Other Names:
  • MEG-3
  • 40/20 (EPA/DHA)ethyl esters fish oil capsules
ACTIVE_COMPARATOR: Placebo
This study will use a randomized placebo-controlled double-blind design and the intervention period will be 6 months. Participants will be instructed to consume 4 x 1285 mg capsules/d, two capsules with each of the main daily meals. The placebo will be composed of 50:50% corn/soybean oil as used in other randomized placebo-controlled trials.
Dietary supplement: corn/soybean oil placebo
This study will use a randomized placebo-controlled double-blind design and the intervention period will be 6 months. Participants will be instructed to consume 4x 1285 mg capsules/d, two capsulesat breackfast and two capsules at dinner. The placebo will be composed of corn/soybean oil as used in other randomized placebo-controlled trials.
Other Names:
  • Meg-3 40:20 EPA:DHA ethyl esters

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from Baseline in cognition
Time Frame: baseline and 6 months
Evaluate change in visuospatial, verbal fluency or working memory with dietary intake (placebo or fish oil treatment.
baseline and 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
DHA level in plasma at baseline
Time Frame: baseline
Evaluate DHA level in plasma lipids at baseline by age and by APOE genotype
baseline
Monthly DHA metabolism
Time Frame: once per month for 6 month
Evaluate each month EPA and DHA level in plasma lipids and in lipoproteins
once per month for 6 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Université de Sherbrooke

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Laval University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 2, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 2, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 14, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 21, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRSC-2012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

A description of the type of data required by other researchers will need approuval by Melanie Plourde. If biological samples are required by other researchers, they will need to get an ethical approuval by our research ethic committee.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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