Trial Information

VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL

VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL is a randomized
clinical trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3
fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the
prevention of depression in older adults. Existing data from laboratory studies,
epidemiologic research, limited clinical trials research suggest that these nutritional
agents may reduce risk of depression or improve mood, but large primary prevention trials
with adequate dosing and lengthy treatment durations in general populations are lacking.

Eligible participants will be assigned by chance (like a coin toss) to one of four groups:
(1) daily vitamin D3 and omega-3; (2) daily vitamin D3 and omega-3 placebo; (3) daily
vitamin D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo.
Participants have an equal chance of being assigned to any of these four groups and a 3 out
of 4 chance of getting at least one active agent.

Participants in all groups will take two pills each day -- one softgel that contains either
vitamin D3 or vitamin D placebo and one capsule that contains either omega-3 or omega-3
placebo. Participants will receive their study pills in convenient calendar packages via
U.S. mail.

Participants will also fill out a short (15-20 minute) questionnaire each year. The
questionnaire asks about health; lifestyle habits such as physical exercise, diet, and
smoking; use of medications and dietary supplements; family history of illness, and new
medical diagnoses. The questionnaire also includes specific questions pertaining to mood.
Occasionally, participants may receive a phone call from study staff to collect information
or to clarify responses on the questionnaire.

Primary aims of 1) reduction in risk of clinical depressive syndrome and 2) yielding of
better mood scores over time will be address in the full VITAL cohort of 20,000. Secondary
aims will be addressed in sub-set of participants. The secondary aims will address whether:
1) among a subset of 1,000 participants evaluated at a Clinical and Translational Science
Center (CTSC), the agents reduce risk of depression and yield better mood scores among
persons with known risk factors for late-life depression; 2) among a subset of 1,000
participants evaluated at a CTSC, the agents reduce risk of major depression and yield
better mood scores among persons with sub-syndromal depressive symptoms; 3) among all VITAL
participants, African-American race (African-Americans have high risk of Vitamin D
deficiency) modifies effects of vitamin D3 supplementation on late-life depression risk and
on mood scores; 4) among a subset of participants, baseline plasma levels of vitamin D and
omega-3 fatty acids are related to depression risk and/or modify agent effects.

Thus, VITAL-DEP will address simultaneously the impact of both vitamin D and fish oil for
universal, selective and indicated prevention of late-life depression.