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

February 17, 2023 updated by: Olivia Okereke, Brigham and Women's Hospital
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

18353

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vitamin D + fish oil placebo

Vitamin D3 (cholecalciferol), 2000 IU per day

Fish oil placebo
Dietary supplement: Fish oil placebo
Fish oil placebo
Dietary supplement: vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day
Other Names:
  • cholecalciferol
Active Comparator: Vitamin D placebo + fish oil

Vitamin D placebo

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])
Dietary supplement: Vitamin D placebo
Vitamin D placebo
Drug: omega-3 fatty acids (fish oil)
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
Active Comparator: Vitamin D placebo + fish oil placebo

Vitamin D placebo

Fish oil placebo
Dietary supplement: Fish oil placebo
Fish oil placebo
Dietary supplement: Vitamin D placebo
Vitamin D placebo
Active Comparator: Vitamin D + fish oil

Vitamin D3 (cholecalciferol), 2000 IU per day

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])
Dietary supplement: vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day
Other Names:
  • cholecalciferol
Drug: omega-3 fatty acids (fish oil)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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).
Baseline, follow-up year 1, follow-up year 2, follow-up year 3, follow-up year 4, and follow-up year 5

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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
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).
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Olivia I Okereke, MD, SM, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

December 31, 2021

Study Completion (Anticipated)

February 1, 2025

Study Registration Dates

First Submitted

September 24, 2012

First Submitted That Met QC Criteria

September 28, 2012

First Posted (Estimate)

October 1, 2012

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

February 17, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-P-001881
  • R01MH091448 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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