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NCT Number: NCT01696435

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

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing randomized clinical trial in 25,871 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: 1) reduces risk of clinical depressive syndrome, 2) yields better mood scores over time, compared to placebo.

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Key information

Conditions

Depression Behavior Behavioral Symptoms Depressive Symptoms Mood

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Participants in VITAL (NCT 01169259) who meet the following criteria are eligible to participate in this ancillary study. These are the criteria specific for testing of the primary aims in the VITAL-DEP ancillary study:

  • no current significant depressive symptoms
  • no core major depressive disorder symptoms for a period of two or more weeks in the past two years
  • no history of alcohol and/or substance abuse disorder active in the past 12 months, schizophrenia or other primary psychotic disorder, bipolar disorder, post-traumatic stress disorder or obsessive-compulsive disorder
  • no current psychotherapy or current use of psychotropics (including non-prescription agents for the treatment of mood disorders), except for limited use of mild sedatives/hypnotics
  • no history of major neurologic disorder or delirium episode in the past 12 months
  • no history of clinical (i.e., overt and not sub-clinical) hypothyroidism diagnosis

Treatment and study plan

Vitamin D3

Dietary Supplement

Vitamin D3 (cholecalciferol), 2000 IU per day

Other names: cholecalciferol

omega-3 fatty acids (fish oil)

Drug

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]).

Other names: fish oil

Fish oil placebo

Dietary Supplement

Fish oil placebo

Vitamin D placebo

Dietary Supplement

Vitamin D placebo

Primary outcomes

  1. Number of Participants With a Depression Event

    Time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up

    Depression syndrome will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (e.g., PHQ) items. This is an event outcome, where the depression event was defined as a new self-report of physician/clinician-diagnosed depression, treatment (medication and/or counseling) for depression, or presence of clinically relevant depressive symptoms (PHQ-8 total score >=10 points) on the annual study questionnaires that were administered over a median 5.3 years of randomized treatment and follow-up. Participants were followed for the depression event until the occurrence of the endpoint, death, or the end of the trial, whichever came first. The Outcome Measure table shows the counts of depression events in each randomized group by treatment.

  2. Mood Scores

    Time frame: Baseline, follow-up year 1, follow-up year 2, follow-up year 3, follow-up year 4, and follow-up year 5

    Mood scores are evaluated by the 8-item Patient Health Questionnaire (PHQ-8). The measured outcome was the total PHQ-8 score. The PHQ-8 includes items corresponding to the criteria for major depression. Each of the 8 items can be scored as 0, 1, 2, or 3 points (higher score means worse symptoms). The 8 items are summed to a total PHQ-8 score. The range for the PHQ-8 score is 0-24 points; higher scores denote worse mood or depressive symptoms. The PHQ-8 was measured annually at baseline and at up to 5 follow-up times (for a maximum of 6 time points). Data from all time points was used to determine the mean differences in change in mood scores over all follow-up by randomized treatment. Per protocol, the Statistical Analysis section shows the results for the primary outcome of mean difference in overall change in PHQ-8 scores comparing active and placebo groups (for each agent).

Other outcomes

  1. Number of Participants With an Incident Depression Event

    Time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up

    Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 >=10 points).

  2. Number of Participants With a Recurrent Depression Event

    Time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up

    Post-hoc Outcome. Recurrent depression is defined as depression cases that occurred among those with past history of depression, but not under treatment or active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 >=10 points).

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Acronym: VITAL-DEP

Important dates

Study start
2010
Primary completion
2021
Study completion
2025
First posted
Oct 1, 2012
Registry last updated
Dec 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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