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

• ClinicalTrials.gov Identifier: NCT01696435
• Recruitment Status: Active, not recruiting
• First Posted: October 1, 2012
• Results First Posted: March 14, 2023
• Last Update Posted: March 14, 2023
• Sponsor: Brigham and Women's Hospital
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Olivia Okereke, Brigham and Women's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Depression; Depressive Symptoms; Mood	Dietary Supplement: vitamin D3; Drug: omega-3 fatty acids (fish oil); Dietary Supplement: Fish oil placebo; Dietary Supplement: Vitamin D placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18353 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL
• Study Start Date: July 2010
• Actual Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: February 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Vitamin D + fish oil placebo; Vitamin D3 (cholecalciferol), 2000 IU per day Fish oil placebo	Dietary Supplement: vitamin D3; Vitamin D3 (cholecalciferol), 2000 IU per day; Other Name: cholecalciferol; Dietary Supplement: Fish oil placebo; Fish oil placebo
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])	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 Name: fish oil; Dietary Supplement: Vitamin D placebo; Vitamin D placebo
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 Name: 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 Name: fish oil

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures:

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).

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Brigham and Women's Hospital

National Institute of Mental Health (NIMH)

Investigators

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

  Study Documents (Full-Text)

Documents provided by Olivia Okereke, Brigham and Women's Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] March 27, 2012

More Information

Additional Information:

Welcome to the VITAL study website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Okereke OI, Vyas CM, Mischoulon D, Chang G, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Reynolds CF 3rd, Manson JE. Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2021 Dec 21;326(23):2385-2394. doi: 10.1001/jama.2021.21187.

Kang JH, Vyas CM, Okereke OI, Ogata S, Albert M, Lee IM, D'Agostino D, Buring JE, Cook NR, Grodstein F, Manson JE. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial. Sci Rep. 2021 Dec 1;11(1):23253. doi: 10.1038/s41598-021-02485-8.

Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Vyas CM, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Manson JE. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020 Aug 4;324(5):471-480. doi: 10.1001/jama.2020.10224.

Donneyong M, Reynolds C, Mischoulon D, Chang G, Luttmann-Gibson H, Bubes V, Guilds M, Manson J, Okereke O. Protocol for studying racial/ethnic disparities in depression care using joint information from participant surveys and administrative claims databases: an observational cohort study. BMJ Open. 2020 Jan 7;10(1):e033173. doi: 10.1136/bmjopen-2019-033173.

Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Cook NR, Copeland T, Friedenberg G, Buring JE, Manson JE. The VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention (VITAL-DEP): Rationale and design of a large-scale ancillary study evaluating vitamin D and marine omega-3 fatty acid supplements for prevention of late-life depression. Contemp Clin Trials. 2018 May;68:133-145. doi: 10.1016/j.cct.2018.02.017. Epub 2018 Mar 8.

• Responsible Party: Olivia Okereke, Olivia I. Okereke, MD, SM, Principal Investigator, Brigham and Women's Hospital, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01696435
• Other Study ID Numbers: 2010-P-001881; R01MH091448 ( U.S. NIH Grant/Contract )
• First Posted: October 1, 2012
• Results First Posted: March 14, 2023
• Last Update Posted: March 14, 2023
• Last Verified: February 2023

Keywords provided by Olivia Okereke, Brigham and Women's Hospital:

Depression; Depressive Symptoms; Mood; Geriatric; Prevention

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents