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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cognitive Decline

Intervention / Treatment
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* Dietary Supplement: vitamin D3
* Drug: omega-3 fatty acids (fish oil)
* Dietary Supplement: Vitamin D3 placebo
* Dietary Supplement: Fish oil placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 92 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids<br>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<br>* Vitamin D3 (cholecalciferol), 2000 IU per day<br>* Other names: cholecalciferol;Drug: omega-3 fatty acids (fish oil)<br>* 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]).<br>|
| Active Comparator: ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids<br>ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day | Dietary Supplement: vitamin D3<br>* Vitamin D3 (cholecalciferol), 2000 IU per day<br>* Other names: cholecalciferol;Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>|
| Active Comparator: PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids<br>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]). | Drug: omega-3 fatty acids (fish oil)<br>* 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]).<br>Dietary Supplement: Vitamin D3 placebo<br>* Vitamin D placebo<br>|
| Placebo Comparator: PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids<br>PLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day | Dietary Supplement: Vitamin D3 placebo<br>* Vitamin D placebo<br>Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>|

What is the study measuring?
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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) |