VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture (VITAL) (VITAL)

VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture

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 fish oil (1 gram of omega-3 fatty acids) 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 a sub-cohort of 771 participants in VITAL and will test the efficacy and safety of high-dose vitamin D supplementation vs. placebo on skeletal health and body composition.

Study Overview

• Status: Active, not recruiting
• Conditions: Body Composition; Bone Density; Bone Health
• Intervention / Treatment: Dietary supplement: Vitamin D3 placebo; Dietary supplement: Fish oil placebo; Dietary supplement: omega-3 fatty acids (fish oil); Dietary supplement: Vitamin D3

Detailed Description

The VITAL: Effects on Bone Structure and Architecture is an ancillary study of the parent VITAL. This study has enrolled a sub-cohort of 771 VITAL participants at the NIH-sponsored Harvard Catalyst Clinical and Translational Science Center (CTSC). The following measurements will be performed at baseline and 2 years post-randomization to determine whether high-dose vitamin D supplementation vs. placebo: 1) produces small increases or reduces bone loss in spine, hip, and total body areal bone density as assessed by dual x-ray absorptiometry (DXA); 2) reduces bone turnover as assessed by biomarkers of bone resorption and formation; 3) improves (a) volumetric bone mineral density (vBMD) and measures of bone structure as assessed by peripheral quantitative computed tomography (pQCT) and (b) bone microarchitecture as assessed by high resolution pQCT (HR-pQCT) at the distal radius and tibia as well as trabecular bone score (TBS) at the spine; and 4) results in changes in body composition as assessed by DXA. Parallel assessments of the effects of omega-3 fatty acids will be performed. This study may elucidate the mechanisms through which high-dose vitamin D may prevent age-related fractures and provide new insights into the role of vitamin D on skeletal health and body composition.

We are currently analyzing the effects of daily dietary supplements of fish oil (1 gram of omega-3 fatty acids) vs. placebo on skeletal health and body composition.

• Study Type: Interventional
• Enrollment (Actual): 771
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Participants in VITAL (NCT 01169259) who meet the following criteria are eligible to participate in this ancillary study:

• Those who are using bisphosphonates currently or within the past 2 years, or other bone-active medications currently or within the past year are not eligible for this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vitamin D placebo + fish oil placebo; Daily vitamin D placebo and daily fish oil placebo	Dietary supplement: Vitamin D3 placebo; Vitamin D placebo; Dietary supplement: Fish oil placebo; Fish oil placebo
Active Comparator: Vitamin D placebo + fish oil; Daily vitamin D placebo and daily fish oil capsule (1 g/d; EPA + DHA in a 1.2:1 ratio)	Dietary supplement: Vitamin D3 placebo; Vitamin D placebo; Dietary supplement: 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]).
Active Comparator: Vitamin D + fish oil placebo; Daily vitamin D (2,000 IU/d) and daily 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 + fish oil; Daily vitamin D (2,000 IU/d) and daily fish oil capsule (1 g/d; EPA + DHA in a 1.2:1 ratio)	Dietary supplement: 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]).; Dietary supplement: Vitamin D3; Vitamin D3 (cholecalciferol), 2000 IU per day.; Other Names: cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bone Density	To determine whether vitamin D supplementation produces small increases or reduces bone loss in spine, hip, and total body areal bone density, as assessed by DXA. Reported values are rounded up.	2 years
Bone Turnover P1NP	To determine whether vitamin D supplementation reduces bone turnover, assessed biomarkers of bone formation (propeptide of type 1 collagen [P1NP]).	2 years
Bone Turnover Beta Crosslaps	To determine whether vitamin D supplementation reduces bone turnover, assessed biomarkers of bone resorption (beta crosslaps).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bone Structure	To determine whether vitamin D supplementation results in changes in bone structure.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Composition	To determine whether vitamin D supplementation results in changes in body composition as assessed by DXA: total body fat and lean mass, and fat mass index and lean mass index, regional fat and lean mass and derived ratios.	2 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Meryl S LeBoff, M.D., Brigham and Women's Hospital

Publications and helpful links

General Publications

• LeBoff MS, Yue AY, Copeland T, Cook NR, Buring JE, Manson JE. VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2015 Mar;41:259-68. doi: 10.1016/j.cct.2015.01.007. Epub 2015 Jan 24.
• Donlon CM, LeBoff MS, Chou SH, Cook NR, Copeland T, Buring JE, Bubes V, Kotler G, Manson JE. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture. Contemp Clin Trials. 2018 Apr;67:56-67. doi: 10.1016/j.cct.2018.02.003. Epub 2018 Feb 23.
• Goldman AL, Donlon CM, Cook NR, Manson JE, Buring JE, Copeland T, Yu CY, LeBoff MS. VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men. Osteoporos Int. 2018 Nov;29(11):2505-2515. doi: 10.1007/s00198-018-4633-3. Epub 2018 Jul 18.
• LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020 May;35(5):883-893. doi: 10.1002/jbmr.3958. Epub 2020 Jan 30.
• Chou SH, Murata EM, Yu C, Danik J, Kotler G, Cook NR, Bubes V, Mora S, Chandler PD, Tobias DK, Copeland T, Buring JE, Manson JE, LeBoff MS. Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL). J Clin Endocrinol Metab. 2021 Apr 23;106(5):1377-1388. doi: 10.1210/clinem/dgaa981.
• LeBoff MS, Murata EM, Cook NR, Cawthon P, Chou SH, Kotler G, Bubes V, Buring JE, Manson JE. VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population. J Clin Endocrinol Metab. 2020 Sep 1;105(9):2929-38. doi: 10.1210/clinem/dgaa311.

Helpful Links

• VITAL Study Website

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): December 1, 2017
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: December 7, 2012
• First Submitted That Met QC Criteria: December 10, 2012
• First Posted (Estimated): December 11, 2012

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2012P000560; 1R01AR059775-01A1 (U.S. NIH Grant/Contract); 5R01AR060574-03 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No