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Cognitive substudy of the vitamin d and omega-3 trial (VITAL-Cog): Design of a large randomized trial of omega-3 and vitamin d supplements in relation to cognitive change

      Background

      Marine omega-3 fatty acids and vitamin D may be associated with improved cognitive function in older persons. However, there are no large, long-term primary prevention trials, especially in African Americans.

      Methods

      The VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2 x 2 factorial trial of long-chain omega-3 fatty acid (Omacor fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) and vitamin D (in the form of vitamin D(3) [cholecalciferol], 2000 IU/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 healthy, U.S. men aged ≥ 50 and women aged ≥ 55, respectively. The mean treatment period will be 5 years. Baseline blood samples were collected in 16,954 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurrence of endpoints, and cancer and vascular risk factors. Deaths will be ascertained through national registries and other sources. VITAL-Cog is an ancillary trial, leveraging the resources of VITAL, to evaluate whether these agents influence cognitive change in a subset of older participants.

      Results

      The primary endpoint of VITAL-Cog is change in cognitive function as assessed by validated telephone cognitive interviews consisting of a battery of 7 tests measuring episodic memory, fluency, executive function and attention). Cognitive function will be estimated by change from baseline in the treatment versus placebo groups on a composite score derived from the cognitive battery. In VITAL-Cog, we have completed baseline cognitive assessments and have initiated the first 2-year follow-up assessments, among 3,500 randomized participants aged 60+ years (3000 with blood), including 600 African Americans. We will also evaluate the effects of these agents by race, APOE e4 status, and baseline plasma 25-hydroxy vitamin D (25(OH)D) and plasma EPA+DHA levels.

      Conclusions

      The VITAL-Cog study is a highly cost-effective, ancillary study of an ongoing parent trial for the evaluation of omega-3 fatty acids and vitamin D, in delaying cognitive change, a goal of major public health importance.