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

Rheumatoid Arthritis Clinical Trial

— VITAL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01351805
• Other study ID #: R01AR059086
• Secondary ID: R01AR059086
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 2010
• Est. completion date: February 2025

Study information

• Verified date: September 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25871
• Est. completion date: February 2025
• Est. primary completion date: November 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Autoimmune Diseases
• Inflammation
• Knee Pain Chronic
• Osteoarthritis
• Rheumatoid Arthritis
• Systemic Inflammatory Process

Intervention

Drug:
• Fish Oil
Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).

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

Other:
• placebo pill
placebo

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Costenbader KH, MacFarlane LA, Lee IM, Buring JE, Mora S, Bubes V, Kotler G, Camargo CA Jr, Manson JE, Cook NR. Effects of One Year of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Biomarkers of Systemic Inflammation in Older US Adults. Clin — View Citation

Hahn J, Cook NR, Alexander EK, Friedman S, Walter J, Bubes V, Kotler G, Lee IM, Manson JE, Costenbader KH. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022 Jan 26;376:e06 — View Citation

MacFarlane LA, Cook NR, Kim E, Lee IM, Iversen MD, Gordon D, Buring JE, Katz JN, Manson JE, Costenbader KH. The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial. Ar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6)	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.	Baseline and 1 year
Primary	Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP)	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.	Baseline and 1 year
Primary	Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2)	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.	Baseline and 1 year
Primary	Incident Autoimmune Diseases	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 years
Primary	Severity of Knee Pain in Subsample With Chronic, Frequent Knee Pain at Baseline- With n-3 FA & Vitamin D	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	Baseline and 5 years
Secondary	Incident Autoimmune Disease	Development of new autoimmune disease through observational follow-up after trial termination.	extension of follow-up through 7 years post trial closure

External Links

•   Welcome to the VITAL Study Website