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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Bone Density, Body Composition, Bone Health

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 placebo
* Dietary Supplement: Fish oil placebo
* Dietary Supplement: omega-3 fatty acids (fish oil)
* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vitamin D placebo + fish oil placebo<br>Daily vitamin D placebo and daily fish oil placebo | Dietary Supplement: Vitamin D3 placebo<br>* Vitamin D placebo<br>Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>|
| Active Comparator: Vitamin D placebo + fish oil<br>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<br>* Vitamin D placebo<br>Dietary Supplement: omega-3 fatty acids (fish oil)<br>* 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]).<br>|
| Active Comparator: Vitamin D + fish oil placebo<br>Daily vitamin D (2,000 IU/d) and daily fish oil placebo | Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>Dietary Supplement: Vitamin D3<br>* Vitamin D3 (cholecalciferol), 2000 IU per day.<br>* Other names: cholecalciferol;|
| Active Comparator: Vitamin D + fish oil<br>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)<br>* 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]).<br>Dietary Supplement: Vitamin D3<br>* Vitamin D3 (cholecalciferol), 2000 IU per day.<br>* Other names: cholecalciferol;|

What is the study measuring?
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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 |