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

Not Applicable

Completed

Conditions: Cognitive Decline

Interventions: Dietary Supplement: vitamin D3
Drug: omega-3 fatty acids (fish oil)
Dietary Supplement: Fish oil placebo
Dietary Supplement: Vitamin D3 placebo

Registration Number: NCT01669915

Lead Sponsor: Brigham and Women's Hospital

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3424

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids	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 + ACTIVE Omega-3 Fatty Acids	vitamin D3	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	vitamin D3	ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day
ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids	Fish oil placebo	ACTIVE 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	omega-3 fatty acids (fish oil)	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 \[DHA\]).
PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids	Vitamin D3 placebo	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 \[DHA\]).
PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids	Vitamin D3 placebo	PLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day
PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids	Fish oil placebo	PLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day

Primary Outcome Measures

Name	Time	Method
Change in Global Composite Score for Cognitive Decline	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.

Secondary Outcome Measures

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