HealthyMOP201109NCT01625195
Causal Relationships Between LC-omega-3-enriched Diet and Cognition
A study testing omega-3 fatty acid supplementation in people with Healthy, run by Université de Sherbrooke at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- omega-3 fatty acid supplementation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 273 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2012to 2 Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- male and female subjects aged between 20-80 years old
Who cannot join
- 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,
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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:
- 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.
- Conditions
- Healthy
- Being tested
- omega-3 fatty acid supplementation, corn/soybean oil placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omega-3 fatty acid supplementationDietary supplement
Also called MEG-3, 40/20 (EPA/DHA)ethyl esters fish oil capsules
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.
corn/soybean oil placeboDietary supplement
Also called Meg-3 40:20 EPA:DHA ethyl esters
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.
| Study group | Role | What they receive |
|---|---|---|
| Omega-3 fatty acid supplement | Placebo comparator | 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. Receives: Dietary Supplement: omega-3 fatty acid supplementation |
| Placebo | Active comparator | 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. Receives: Dietary Supplement: corn/soybean oil placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in cognition
Evaluate change in visuospatial, verbal fluency or working memory with dietary intake (placebo or fish oil treatment.
Measured: baseline and 6 months
Secondary outcomes (2)
DHA level in plasma at baseline
Evaluate DHA level in plasma lipids at baseline by age and by APOE genotype
Measured: baseline
Monthly DHA metabolism
Evaluate each month EPA and DHA level in plasma lipids and in lipoproteins
Measured: once per month for 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2012 (estimated)
- Study start1 May 2012
- Primary completion2 Apr 2017
- Study completion2 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 273 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Laval University
- Responsible party
- Principal investigator, Mélanie Plourde, Université de Sherbrooke
- Investigators
- Melanie Plourde, Ph.D., Principal investigator, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01625195
- Sponsor's protocol ID
- IRSC-2012
- Acronym
- MOP201109
- Status last verified
- May 2020
- First submitted
- 14 Jun 2012
- Last updated
- 8 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: 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.
Publications
Loukil I, Aguilera EC, Vachon A, Leveille P, Plourde M. Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid-Eicosapentaenoic Acid Response During an omega-3 Fatty Acid Supplementation: A Secondary Analysis. J Nutr. 2024 May;154(5):1561-1570. doi: 10.1016/j.tjnut.2024.03.013. Epub 2024 Mar 19.
PubMed 38513888
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Causal Relationships Between LC-omega-3-enriched Diet and Cognition
- ClinicalTrials.gov ID
- NCT01625195
- Acronym / sponsor ID
- MOP201109 / IRSC-2012
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 273 participants (actual)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- Laval University
- Study start
- 1 May 2012 (actual)
- Primary completion
- 2 Apr 2017 (actual)
- Study completion
- 2 Dec 2017 (actual)
- First posted
- 21 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Omega-3 fatty acid supplement | Placebo comparator | Dietary Supplement: omega-3 fatty acid supplementationThis 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. |
| Placebo | Active comparator | Dietary Supplement: corn/soybean oil placeboThis 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. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- male and female subjects aged between 20-80 years old
Key exclusion criteria (19 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| omega-3 fatty acid supplementationAlso: MEG-3, 40/20 (EPA/DHA)ethyl esters fish oil capsulesThis 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. | Dietary supplement | Omega-3 fatty acid supplement |
| corn/soybean oil placeboAlso: Meg-3 40:20 EPA:DHA ethyl estersThis 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. | Dietary supplement | Placebo |
Primary outcome
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.
2 secondary outcomes
DHA level in plasma at baseline
Time frame: baseline
Monthly DHA metabolism
Time frame: once per month for 6 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2020.
- Derived from this study: PubMed 38513888Loukil I, Aguilera EC, Vachon A, Leveille P, Plourde M. Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid-Eicosapentaenoic Acid Response During an omega-3 Fatty Acid Supplementation: A Secondary Analysis. J Nutr. 2024 May;154(5):1561-1570. doi: 10.1016/j.tjnut.2024.03.013. Epub 2024 Mar 19.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melanie Plourde, Ph.D. principal investigator
Université de Sherbrooke
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing omega-3 fatty acid supplementation in people with Healthy, run by Université de Sherbrooke at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in cognition (time frame: baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01625195, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2020.