Cognitive DeclineVITAL-CogNCT01669915

A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline

A study testing vitamin D3 and omega-3 fatty acids (fish oil) in people with Cognitive Decline, run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 60 to 92 yearsHealthy volunteers can take part
Conditions the study is for: Cognitive Decline
What is being tested?: vitamin D3 and omega-3 fatty acids (fish oil)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 3,424 participants
Where: 1 siteUnited States
Study dates: 14 Sep 2011to 31 Dec 2021
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 60 to 92 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Participants in VITAL (NCT 01169259) who meet the following criteria are eligible to participate in this ancillary study:

are aged 60 or more
have no hearing impairment
indicate a willingness on the run-in phase to participate in a cognitive sub-study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing randomized clinical trial in 25,875 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study is being conducted among participants in VITAL and will examine whether vitamin D or fish oil is associated with cognitive decline in 3000 older participants of VITAL.

Read the detailed description

Primary aim of annual rate of cognitive decline. Secondary aims will be addressed in sub-set of participants: 1) among participants, African-American race (African-Americans have high risk of Vitamin D deficiency) modifies effects of vitamin D3 supplementation on cognitive decline; 2) among a subset of participants, baseline plasma levels of vitamin D and omega-3 fatty acids modify agent effects.

Conditions: Cognitive Decline
Being tested: vitamin D3, omega-3 fatty acids (fish oil), Vitamin D3 placebo, Fish oil placebo
Medical subject headings: Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

vitamin D3Dietary supplement
Also called cholecalciferol
Vitamin D3 (cholecalciferol), 2000 IU per day
omega-3 fatty acids (fish oil)Drug
Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Vitamin D3 placeboDietary supplement
Vitamin D placebo
Fish oil placeboDietary supplement
Fish oil placebo

Study groups in NCT01669915
Study group	Role	What they receive
ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids	Active comparator	ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; ACTIVE Omega-3 Fatty Acids = Omacor, one 1-gram capsule/day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]). Receives: Dietary Supplement: vitamin D3; Drug: omega-3 fatty acids (fish oil)
ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids	Active comparator	ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day Receives: Dietary Supplement: vitamin D3; Dietary Supplement: Fish oil placebo
PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids	Active comparator	PLACEBO Vitamin D, one capsule/day; ACTIVE Omega-3 Fatty Acids = Omacor, one 1-gram capsule/day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]). Receives: Drug: omega-3 fatty acids (fish oil); Dietary Supplement: Vitamin D3 placebo
PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids	Placebo comparator	PLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day Receives: Dietary Supplement: Vitamin D3 placebo; Dietary Supplement: Fish oil placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Global Composite Score for Cognitive Decline
We administered by telephone, eight cognitive tests (1.Telephone Interview of Cognitive Status (TICS); 2.Delayed recall of the TICS 10-word list; 3.East Boston Memory Test (EBMT); 4.Delayed recall of the EBMT; 5.Category fluency test (animal naming test); 6.Oral Trail Making Test (OTMT-Part A); 7. OTMT-Part B; 8.Digit span backwards). The primary endpoint was the change over time (last assessment score minus the baseline assessment score) in GLOBAL COMPOSITE SCORE (average of Z-scores of component tests); for both baseline and last assessment Z-scores, a mean Z-score of 0 represents the mean and the higher the Z-score, the better the overall cognitive performance across the tests. The primary endpoint was a difference of two Z-scores, so a value of 0 means no change over time, a positive value means an increase over time and a negative value means a decrease (or "decline") over time, for clinical significance, 1 year of aging is associated with a primary endpoint value of -0.004.
Measured: Change over two assessments (baseline, 2.8 years).

Secondary outcomes (3)

Change in Episodic Memory Score for Cognitive Decline
The outcome measure was change over time (last assessment score minus the baseline assessment score) in the EPISODIC MEMORY SCORE combining z-scores of 4 tests: the immediate and delayed recalls of both the East Boston Memory Test (EBMT) and the Telephone Interview of Cognitive Status (TICS) 10-word list; for both baseline and last assessment Z-scores, a mean Z-score of 0 represents the mean and the higher the Z-score, the better the overall cognitive performance across the tests. The primary endpoint was a difference of two Z-scores, so a value of 0 means no change over time, a positive value means an increase over time and a negative value means a decrease (or "decline") over time, for clinical significance, 1 year of aging is associated with a primary endpoint value of -0.01.
Measured: Change over two assessments (baseline, 2.8 years)
Change in Executive Function Score for Cognitive Decline
The outcome measure is change over time (last assessment score minus the baseline assessment score) in the EXECUTIVE FUNCTION SCORE combining z-scores of 4 tests: category fluency (animal naming), digit span backwards, and Oral Trails Making Test (OTMT)-Part A and OTMT-Part B; for both baseline and last assessment Z-scores, a mean Z-score of 0 represents the mean and the higher the Z-score, the better the overall cognitive performance across the tests. The primary endpoint was a difference of two Z-scores, so a value of 0 means no change over time, a positive value means an increase over time and a negative value means a decrease (or "decline") over time, for clinical significance, 1 year of aging is associated with a primary endpoint value of +0.006.
Measured: Change over two assessments (baseline, 2.8 years)
Change in Telephone Interview of Cognitive Status (TICS) for Cognitive Decline.
Change over time (last assessment score minus the baseline assessment score) on the TICS (0-41 points), a measure of general cognition. A higher value on the TICS represents better cognitive performance; for clinical significance, 1 year of aging is associated with a primary endpoint value of -0.05
Measured: Change over two assessments (baseline, 2.8 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Sep 201131 Dec 2021

First posted21 Aug 2012 (estimated)
Study start14 Sep 2011
Primary completion8 Jun 2016
Study completion31 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cognitive DeclineStudies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe 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: Factorial
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 3,424 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01669915
Sponsor's protocol ID: 2010P-000769
Other IDs: R01AG036755
Acronym: VITAL-Cog
Status last verified: Mar 2023
First submitted: 17 Aug 2012
Last updated: 21 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kang JH, Vyas CM, Okereke OI, Ogata S, Albert M, Lee IM, D'Agostino D, Buring JE, Cook NR, Grodstein F, Manson JE. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial. Sci Rep. 2021 Dec 1;11(1):23253. doi: 10.1038/s41598-021-02485-8.
PubMed 34853363

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline
ClinicalTrials.gov ID: NCT01669915
Acronym / sponsor ID: VITAL-Cog / 2010P-000769
Conditions: Cognitive Decline
Study type: Interventional
Recruitment status: Completed
Enrolment: 3,424 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: National Institute on Aging (NIA)
Study start: 14 Sep 2011 (actual)
Primary completion: 8 Jun 2016 (actual)
Study completion: 31 Dec 2021 (actual)
First posted: 21 Aug 2012 (estimated)
Results: Posted 21 Apr 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids	Active comparator	Dietary Supplement: vitamin D3, Drug: omega-3 fatty acids (fish oil)ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; ACTIVE Omega-3 Fatty Acids = Omacor, one 1-gram capsule/day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids	Active comparator	Dietary Supplement: vitamin D3, Dietary Supplement: Fish oil placeboACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day
PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids	Active comparator	Drug: omega-3 fatty acids (fish oil), Dietary Supplement: Vitamin D3 placeboPLACEBO Vitamin D, one capsule/day; ACTIVE Omega-3 Fatty Acids = Omacor, one 1-gram capsule/day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids	Placebo comparator	Dietary Supplement: Vitamin D3 placebo, Dietary Supplement: Fish oil placeboPLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day

Who may qualify

Ages: 60 to 92 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

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
vitamin D3Also: cholecalciferolVitamin D3 (cholecalciferol), 2000 IU per day	Dietary supplement	ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids, ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids
omega-3 fatty acids (fish oil)Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).	Drug	ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids, PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids
Vitamin D3 placeboVitamin D placebo	Dietary supplement	PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids, PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids
Fish oil placeboFish oil placebo	Dietary supplement	ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids, PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids

Primary outcome

Change in Global Composite Score for Cognitive Decline
Time frame: Change over two assessments (baseline, 2.8 years).
We administered by telephone, eight cognitive tests (1.Telephone Interview of Cognitive Status (TICS); 2.Delayed recall of the TICS 10-word list; 3.East Boston Memory Test (EBMT); 4.Delayed recall of the EBMT; 5.Category fluency test (animal naming test); 6.Oral Trail Making Test (OTMT-Part A); 7. OTMT-Part B; 8.Digit span backwards). The primary endpoint was the change over time (last assessment score minus the baseline assessment score) in GLOBAL COMPOSITE SCORE (average of Z-scores of component tests); for both baseline and last assessment Z-scores, a mean Z-score of 0 represents the mean and the higher the Z-score, the better the overall cognitive performance across the tests. The primary endpoint was a difference of two Z-scores, so a value of 0 means no change over time, a positive value means an increase over time and a negative value means a decrease (or "decline") over time, for clinical significance, 1 year of aging is associated with a primary endpoint value of -0.004.

3 secondary outcomes

Change in Episodic Memory Score for Cognitive Decline
Time frame: Change over two assessments (baseline, 2.8 years)
Change in Executive Function Score for Cognitive Decline
Time frame: Change over two assessments (baseline, 2.8 years)
Change in Telephone Interview of Cognitive Status (TICS) for Cognitive Decline.
Time frame: Change over two assessments (baseline, 2.8 years)

Results and safety

Results posted to the registry on 21 Apr 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TELEPHONE INTERVIEW ANCILLARY STUDY: ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids	844	844
TELEPHONE INTERVIEW ANCILLARY STUDY: ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids	866	866
TELEPHONE INTERVIEW ANCILLARY STUDY: PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids	855	855
TELEPHONE INTERVIEW ANCILLARY STUDY: PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids	859	859

Primary outcome: Change in Global Composite Score for Cognitive Decline

Time frame: Change over two assessments (baseline, 2.8 years).. Mean (Standard Error). Unit: Z-score

Measure	TELEPHONE INTERVIEW ANCILLARY STUDY: Active Vitamin D n = 1710	TELEPHONE INTERVIEW ANCILLARY STUDY: Vitamin D Placebo n = 1714	TELEPHONE INTERVIEW ANCILLARY STUDY: Active Omega-3 Fatty Acids n = 1699	TELEPHONE INTERVIEW ANCILLARY STUDY: Omega-3 Fatty Acids Placebo n = 1725
Value	-0.24 (0.01)	-0.25 (0.01)	-0.25 (0.01)	-0.24 (0.01)

TELEPHONE INTERVIEW ANCILLARY STUDY: Active Vitamin D vs TELEPHONE INTERVIEW ANCILLARY STUDY: Vitamin D Placebo: Mean Difference (Net): 0.01 (95% CI -0.01 to 0.02), p = 0.31, Mixed Models Analysis
TELEPHONE INTERVIEW ANCILLARY STUDY: Active Omega-3 Fatty Acids vs TELEPHONE INTERVIEW ANCILLARY STUDY: Omega-3 Fatty Acids Placebo: Mean Difference (Net): -0.01 (95% CI -0.02 to 0.003), p = 0.14, Mixed Models Analysis

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TELEPHONE INTERVIEW ANCILLARY STUDY: Active Vitamin D	138 of 1,710 (8.1%)	1,259 of 1,710 (73.6%)	41 of 1,710
TELEPHONE INTERVIEW ANCILLARY STUDY: Vitamin D Placebo	117 of 1,714 (6.8%)	1,236 of 1,714 (72.1%)	26 of 1,714
TELEPHONE INTERVIEW ANCILLARY STUDY: Active Omega-3 Fatty Acids	134 of 1,699 (7.9%)	1,220 of 1,699 (71.8%)	42 of 1,699
TELEPHONE INTERVIEW ANCILLARY STUDY: Omega-3 Fatty Acids Placebo	121 of 1,725 (7%)	1,275 of 1,725 (73.9%)	25 of 1,725
TELEPHONE INTERVIEW ANCILLARY STUDY: Active Vitamin D/Active Omega-3 Fatty Acids	74 of 844 (8.8%)	600 of 844 (71.1%)	26 of 844
TELEPHONE INTERVIEW ANCILLARY STUDY: Active Vitamin D/Placebo Omega-3 Fatty Acids	64 of 866 (7.4%)	659 of 866 (76.1%)	15 of 866
TELEPHONE INTERVIEW ANCILLARY STUDY: Placebo Vitamin D/Active Omega-3 Fatty Acids	60 of 855 (7%)	620 of 855 (72.5%)	16 of 855
TELEPHONE INTERVIEW ANCILLARY STUDY: Placebo Vitamin D/Placebo Omega-3 Fatty Acids	57 of 859 (6.6%)	616 of 859 (71.7%)	10 of 859

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34853363Kang JH, Vyas CM, Okereke OI, Ogata S, Albert M, Lee IM, D'Agostino D, Buring JE, Cook NR, Grodstein F, Manson JE. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial. Sci Rep. 2021 Dec 1;11(1):23253. doi: 10.1038/s41598-021-02485-8.
VITAL study website linkLink provided by the sponsor.

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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing vitamin D3 and omega-3 fatty acids (fish oil) in people with Cognitive Decline, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 21 Apr 2023. 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 United States. 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?

Yes. Results are posted in the registry (first posted 21 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 in Global Composite Score for Cognitive Decline (time frame: Change over two assessments (baseline, 2.8 years).). 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 NCT01669915, 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 21 Apr 2023.