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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Decline
• Intervention / Treatment: Dietary supplement: Vitamin D3 placebo; Dietary supplement: Fish oil placebo; Dietary supplement: vitamin D3; Drug: omega-3 fatty acids (fish oil)

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.

• Study Type: Interventional
• Enrollment (Actual): 3424
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids; 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]).	Dietary supplement: vitamin D3; Vitamin D3 (cholecalciferol), 2000 IU per day; Other Names: cholecalciferol; Drug: 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]).
Active Comparator: ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids; ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day	Dietary supplement: Fish oil placebo; Fish oil placebo; Dietary supplement: vitamin D3; Vitamin D3 (cholecalciferol), 2000 IU per day; Other Names: cholecalciferol
Active Comparator: PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids; 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]).	Dietary supplement: Vitamin D3 placebo; Vitamin D placebo; Drug: 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]).
Placebo Comparator: PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids; PLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day	Dietary supplement: Vitamin D3 placebo; Vitamin D placebo; Dietary supplement: Fish oil placebo; Fish oil placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Change over two assessments (baseline, 2.8 years).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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	Change over two assessments (baseline, 2.8 years)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General 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.

Helpful Links

• VITAL study website link

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2011
• Primary Completion (Actual): June 8, 2016
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: August 17, 2012
• First Submitted That Met QC Criteria: August 17, 2012
• First Posted (Estimate): August 21, 2012

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2010P-000769; R01AG036755 (U.S. NIH Grant/Contract)