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

NCT01696435 | Completed Results DMC

• 3 other identifiers: 2010-P-001881R01MH091448R56MH091448
• Study Type: interventional
• Target: 18,353
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Depressive Symptoms; Mood

Keywords

Depression; Depressive Symptoms; Mood; Geriatric; Prevention

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Depression Event

  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

  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 Outcomes (2)

• Number of Participants With an Incident Depression Event

  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

  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

Study Arms (4)

Vitamin D + fish oil placebo

ACTIVE COMPARATOR

Vitamin D3 (cholecalciferol), 2000 IU per day Fish oil placebo

Dietary Supplement: vitamin D3; Dietary Supplement: Fish oil placebo

Vitamin D placebo + fish oil

ACTIVE COMPARATOR

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); Dietary Supplement: Vitamin D placebo

Vitamin D placebo + fish oil placebo

ACTIVE COMPARATOR

Vitamin D placebo Fish oil placebo

Dietary Supplement: Fish oil placebo; Dietary Supplement: Vitamin D placebo

Vitamin D + fish oil

ACTIVE COMPARATOR

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; Drug: omega-3 fatty acids (fish oil)

Interventions

vitamin D3 DIETARY_SUPPLEMENT

Vitamin D3 (cholecalciferol), 2000 IU per day

Also known as: cholecalciferol

Vitamin D + fish oil; Vitamin D + fish oil placebo

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 \[DHA\]).

Also known as: fish oil

Vitamin D + fish oil; Vitamin D placebo + fish oil

Fish oil placebo DIETARY_SUPPLEMENT

Fish oil placebo

Vitamin D + fish oil placebo; Vitamin D placebo + fish oil placebo

Vitamin D placebo DIETARY_SUPPLEMENT

Vitamin D placebo

Vitamin D placebo + fish oil; Vitamin D placebo + fish oil placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Related Publications (9)

• Vyas CM, Kang JH, Mischoulon D, Cook NR, Reynolds Iii CF, Chang G, Mora S, De Vivo I, Manson JE, Okereke OI. Apolipoprotein E and Its Association With Cognitive Change and Modification of Treatment Effects of Vitamin D3 and Omega-3s on Cognitive Change: Results From the In-Clinic Subset of a Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2024 Mar 1;79(3):glad260. doi: 10.1093/gerona/glad260.

  PMID: 37952113 DERIVED

• Vyas CM, Mischoulon D, Chang G, Cook NR, Weinberg A, Copeland T, Kang JH, Bubes V, Friedenberg G, LeBoff MS, Lee IM, Buring JE, Manson JE, Reynolds CF, Okereke OI. Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL). J Clin Psychiatry. 2023 Jun 26;84(4):22m14629. doi: 10.4088/JCP.22m14629.

  PMID: 37378490 DERIVED

• Vyas CM, Mischoulon D, Chang G, Reynolds CF 3rd, Cook NR, Weinberg A, Copeland T, Bubes V, Bradwin G, Lee IM, Buring JE, Mora S, Rifai N, Manson JE, Okereke OI. Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention. J Psychiatr Res. 2023 Jul;163:357-364. doi: 10.1016/j.jpsychires.2023.05.069. Epub 2023 May 26.

  PMID: 37267732 DERIVED

• Vyas CM, Sadreyev RI, Gatchel JR, Kang JH, Reynolds CF, Mischoulon D, Chang G, Hazra A, Manson JE, Blacker D, De Vivo I, Okereke OI. Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults. J Alzheimers Dis. 2023;93(4):1563-1575. doi: 10.3233/JAD-230093.

  PMID: 37212116 DERIVED

• 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.

  PMID: 34932079 DERIVED

• 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.

  PMID: 34853363 DERIVED

• 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.

  PMID: 32749491 DERIVED

• 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.

  PMID: 31915172 DERIVED

• 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.

  PMID: 29526608 DERIVED

Related Links

• Welcome to the VITAL study website

MeSH Terms

Conditions

Depression

Interventions

Cholecalciferol; Fatty Acids, Omega-3; Fish Oils

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fatty Acids, Unsaturated; Fatty Acids; Oils

Results Point of Contact

• Title: Dr. Olivia Okereke/Study Principal Investigator
• Organization: Massachusetts General Hospital

olivia.okereke@mgh.harvard.edu

(617) 726-2000

Study Officials

• Olivia I Okereke, MD, SM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Olivia I. Okereke, MD, SM, Principal Investigator, Brigham and Women's Hospital

Study Record Dates

• First Submitted: September 24, 2012
• First Posted: October 1, 2012
• Study Start: July 1, 2010
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2025
• Last Updated: December 10, 2025
• Results First Posted: March 14, 2023

Record last verified: 2025-11

Locations

US (1)