VITamin D and OmegA-3 TriaL: Interrelationship of Vitamin D and Vitamin K on Bone (VITAL)

VITamin D and OmegA-3 TriaL: Interrelationship of Vitamin D and Vitamin K on Bone

Vitamin D supplements are widely promoted for bone health. Both vitamin D and vitamin K are important for deposition of calcium in bone, but little is known about the relationship of vitamin K status and bone health.

Study Overview

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

Detailed Description

The goal of VITAL: Interrelationship of Vitamin D and Vitamin K on Bone is to test whether vitamin K status is associated with incident fractures in a case-cohort design or modifies the randomized effects of vitamin D supplementation vs. placebo on 2-year changes in bone density and structure outcomes.

• Study Type: Interventional
• Enrollment (Actual): 25871
• 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: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

- Participants in VITAL (NCT 01169259) study who met the following criteria of the parent trial are eligible to participate in this ancillary study:

• be men aged 50 years and older or women aged 55 years and older
• have no history of cardiovascular disease or cancer (excluding non-melanoma skin cancer)
• have none of the following: allergy to soy or fish, hypercalcemia, renal failure or dialysis, severe liver disease, hypo- or hyperparathyroidism, sarcoidosis or other granulomatous diseases, or any other serious illnesses
• consume ≤ 1200 mg/d of calcium for the duration of the trial
• consume ≤ 800 IU of vitamin D for duration of the trial
• refrain from taking fish oil supplements for the duration of the trial

Exclusion:

- For aims 2 and 3, 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
Active Comparator: Vitamin D + fish oil	Drug: 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
Active Comparator: Vitamin D + 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 placebo + fish oil	Dietary supplement: Vitamin D3 placebo; Vitamin D placebo; Drug: 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]).
Placebo Comparator: Vitamin D placebo + fish oil placebo	Dietary supplement: Vitamin D3 placebo; Vitamin D placebo; Dietary supplement: Fish oil placebo; Fish oil placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Fractures	The effect of low vitamin K status (with or without vitamin D supplementation) on the number of new total, non-vertebral and hip fractures.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Areal Bone Density	The effect of low vitamin K status (with or without vitamin D supplementation) on changes in areal bone density at the spine and hip between baseline and two years post-randomization.	2 years
Change in Volumetric Bone Mineral Density	The effect of low vitamin K status (with or without vitamin D supplementation) on changes in total, trabecular and cortical volumetric bone mineral density (vBMD) between baseline and two years post-randomization.	2 years
Change in Cortical Thickness	The effect of low vitamin K status (with or without vitamin D supplementation) on changes in cortical thickness assessed by peripheral quantitative computed tomography (pQCT) between baseline and two years post-randomization.	2 years
Change in Bone Strength	The effect of low vitamin K status (with or without vitamin D supplementation) on changes in bone strength measures assessed by peripheral quantitative computed tomography (pQCT) between baseline and two years post-randomization.	2 years
Change in Trabecular Bone Score	The effect of low vitamin K status (with or without vitamin D supplementation) on changes in trabecular bone score between baseline and two years post-randomization.	2 years
Concentration of Urine Calcium	The effect of low vitamin K status (with or without vitamin D supplementation) on change in urine calcium excretion between baseline and two years post-randomization.	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.

Helpful Links

• VITAL Study Website

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Vitamin D; Vitamin K
• 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: 2012P000560-1; 5R01AR060574-03 (U.S. NIH Grant/Contract); 2R01AR059775-06A1 (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