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Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain (VITAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01351805
Recruitment Status : Active, not recruiting
First Posted : May 11, 2011
Results First Posted : January 8, 2021
Last Update Posted : October 13, 2022
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Karen H. Costenbader, Brigham and Women's Hospital

Study Description
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Brief Summary:
The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a 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 VITAL participants and will examine whether vitamin D or fish oil have effects upon A) autoimmune disease incidence, B) biomarkers of systemic inflammation, and C) chronic knee pain. Blood samples at baseline and in follow-up will be collected in a randomly selected subcohort of 1500 individuals and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein, interleukin-6, and tumor necrosis factor-receptor 2. Approximately 1300 individuals with chronic, frequent knee pain will be followed with annual questionnaires to evaluate the effects of the supplements on chronic knee pain.

Condition or disease Intervention/treatment Phase
Autoimmune Diseases Systemic Inflammatory Process Knee Pain Chronic Osteoarthritis Rheumatoid Arthritis Drug: Fish Oil Dietary Supplement: Vitamin D Other: placebo pill Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25871 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain
Actual Study Start Date : July 2010
Actual Primary Completion Date : November 10, 2018
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Fish Oil
Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
 Drug: Fish Oil
Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Other Names:
  • eicosapentaenoic acid (EPA)
  • docosahexaenoic acid (DHA)
  • marine fatty acids
  • omega-3 fatty acids
  • fish oils

Other: placebo pill
placebo
Experimental: Vitamin D
Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.
 Dietary Supplement: Vitamin D
Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.
Other Names:
  • cholecalciferol
  • vitamin D3

Other: placebo pill
placebo
Placebo Comparator: placebo
Subjects will receive placebo pill.
 Other: placebo pill
placebo
Experimental: Vitamin D and Fish Oil
Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
 Drug: Fish Oil
Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Other Names:
  • eicosapentaenoic acid (EPA)
  • docosahexaenoic acid (DHA)
  • marine fatty acids
  • omega-3 fatty acids
  • fish oils

Dietary Supplement: Vitamin D
Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.
Other Names:
  • cholecalciferol
  • vitamin D3


Outcome Measures
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Primary Outcome Measures :
  1. Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6) [ Time Frame: Baseline and 1 year ]
    In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the IL-6 serum biomarker of systemic inflammation.

  2. Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP) [ Time Frame: Baseline and 1 year ]
    In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the CRP serum biomarker of systemic inflammation.

  3. Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2) [ Time Frame: Baseline and 1 year ]
    In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the TNFR2 serum biomarker of systemic inflammation.

  4. Incident Autoimmune Diseases [ Time Frame: 5 years ]

    All participants were followed for the development of new autoimmune diseases, including, but not limited to, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, inflammatory bowel disease and polymyalgia rheumatica. The primary endpoint was all incident autoimmune disease confirmed by extensive medical record review. Participants self-reported all incident autoimmune diseases from baseline through follow-up. We used Cox proportional hazards models to test the effects of vitamin D and n-3 fatty acids upon autoimmune disease incidence.

    We compared the separate main effects of vitamin D or n-3 fatty acid supplement assignment on AD incidence using Cox regression models. To account for randomization stratification and study design, we additionally adjusted for age, sex, self-reported race, and randomization to the other supplement. Person-time was counted until diagnosis of a new confirmed AD, death, or the end of the trial. We also test interactions between the two supplements


  5. Severity of Knee Pain in Subsample With Chronic, Frequent Knee Pain at Baseline- With n-3 FA & Vitamin D [ Time Frame: Baseline and 5 years ]

    Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain was the primary outcome on a scale of 0-100 with 100= worst pain.

    Subsample of VITAL participants with chronic, frequent knee pain at trial baseline were followed with annual WOMAC questionnaires to test for change in severity of chronic knee pain in those taking Omega-3 fish oil (n-3 FA) supplements compared to those taking placebo and for those taking Vitamin D supplements compared to those taking placebo. We tested whether n-3 FA supplements and Vitamin D are associated with reduced levels of WOMAC knee pain at the end of the trial (comparing knee pain outcomes in those receiving supplements to placebo). We will also test whether there were multiplicative interactions between the two supplements for the outcome of knee pain severity by WOMAC-Pain index



Secondary Outcome Measures :
  1. Incident Autoimmune Disease [ Time Frame: extension of follow-up through 7 years post trial closure ]
    Development of new autoimmune disease through observational follow-up after trial termination.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
As for the parent trial, VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259). Individuals with chronic, frequent knee pain at study baseline will be followed as a subcohort. Trial enrollment complete.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01351805


Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Principal Investigator: Karen H Costenbader, MD, MPH Brigham and Women's Hospital
  Study Documents (Full-Text)

Documents provided by Karen H. Costenbader, Brigham and Women's Hospital:
Study Protocol and Statistical Analysis Plan  [PDF] November 9, 2009

More Information
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Additional Information:

Publications of Results:

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Responsible Party: Karen H. Costenbader, Associate Physician, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01351805    
Other Study ID Numbers: R01AR059086 ( U.S. NIH Grant/Contract )
R01AR059086 ( U.S. NIH Grant/Contract )
First Posted: May 11, 2011    Key Record Dates
Results First Posted: January 8, 2021
Last Update Posted: October 13, 2022
Last Verified: September 2022
Keywords provided by Karen H. Costenbader, Brigham and Women's Hospital:
vitamin D
omega-3 fatty acid
fish oil
prevention
trial
autoimmune disease
rheumatoid arthritis
 psoriasis
systemic inflammation
Interleukin-6
C-reactive peptide
tumor necrosis factor
osteoarthritis
Additional relevant MeSH terms:
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Arthritis
Osteoarthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Inflammation
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pathologic Processes
Connective Tissue Diseases
 Immune System Diseases
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents