Vitamin D Supplementation in Warfighters

Genomics of Vitamin D Supplementation and Warfighter Nutritional Resilience

A genomics-based approach will target specific genes that may explain the response in biomarkers and symptoms before and after supplementation. One objective is to generate evidence-based recommendations for vitamin D supplementation in Soldiers who often experience musculoskeletal disorders and immune dysfunction impacting physical performance and military readiness. The investigation is designed to address these specific aims: 1) explore vitamin D status in 105 Service Members to determine common symptoms associated with deficiency; 2) examine the effect of vitamin D levels on gene expression from select genes known to influence metabolism, bone density, and immune function; and 3) evaluate changes in gene expression between groups receiving high or low supplementation, and compare to healthy controls. Follow-up at 15 months will evaluate circulating vitamin D.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency Disease
• Intervention / Treatment: Dietary supplement: Vitamin D3

Detailed Description

A genomics-based approach will target identified candidate genes and search for variants that may explain the response observed in biomarkers and symptoms when deficient individuals are repleted. The long-term objective of this study is to translate findings from next-generation sequencing (NGS) technology into clinically meaningful data regarding vitamin D supplementation for Service Members (SM) who may be at risk for musculoskeletal disorders and immune dysfunction that impacts physical performance and military readiness. We propose the following specific aims: 1) explore the phenotypic expression of vitamin D status in a cohort of SM to determine common symptoms associated with deficiency/insufficiency states; 2) examine the effect of vitamin D levels on broad gene expression from carefully chosen candidate genes known to influence vitamin D status, bone density, and immune function; 3) evaluate changes in gene expression levels between and within groups supplemented with low vs high vitamin D, and compare to healthy controls, and 4) examine the relationship between vitamin D deficiency and the clinically relevant outcomes of stress fracture and high blood pressure before and after supplementation to a therapeutic plasma level of 25(OH)D. This prospective, randomized, double-blind trial will enroll 105 SM in the Northwest to evaluate frequency, symptoms, and genomic expression of vitamin D levels using survey instruments, immunologic and bone biomarkers, and NGS of white blood cells pre- and post-supplementation with oral vitamin D over 3 months. Participant follow-up at 12 months will evaluate maintenance of adequate circulating vitamin D; this timeframe represents a typical deployment period.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- active duty service member, age 18 years or older, ability to read and understand English, not deploying in the next 15 months, and subjectively in good health.

Exclusion Criteria:

- family members, beneficiaries, or civilians, pregnant or currently breastfeeding females, anyone with chronic health problems (e.g. eating disorders, kidney disease, liver disease, intestinal malabsorption), any active duty SM taking >400 IU/day vitamin D supplementation and unwilling to discontinue this, current or healing stress fractures, taking medications for an endocrine disorder, such as synthroid, or those identified as having a high potential for interaction with vitamin D including anti-seizure medications, cyclosporine, and indinavir (Crixivan).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy control group; Subjects in this arm have a normal serum level of 25(OH)D, >30 ng/mL. Subjects submit to blood draws and biometric tests (DXA, body composition, BP) and questionnaires on 3 occasions. They do not receive vitamin D3 supplementation.	Dietary supplement: Vitamin D3; As in Arms; Other Names: Cholecalciferol
Experimental: Low dose supplementation group; Subjects in this group have been identified as having a level of 25(OH)D of < 30 ng/mL and are randomized to receive vitamin D3 supplementation of 2000 IU daily for 3 months.	Dietary supplement: Vitamin D3; As in Arms; Other Names: Cholecalciferol
Experimental: High dose supplementation group; Subjects in this group have been identified as having a level of 25(OH)D of <30 ng/mL and are randomized to receive vitamin D3 supplementation of 5000 IU daily for 3 months.	Dietary supplement: Vitamin D3; As in Arms; Other Names: Cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25(OH)D	Serum measure of 25(OH) at baseline, 3 months, and 15 months	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D gene expression	Gene expression analysis will be used to determine relationship between low and high dose vitamin D supplementation and 25(OH)D levels, blood pressure, bone density, and body fat	3 months

Collaborators and Investigators

• Sponsor: Madigan Army Medical Center
• Collaborators: TriService Nursing Research Program
• Investigators: Principal Investigator: Mary S McCarthy, PhD, Madigan Army Medical Center

Publications and helpful links

General Publications

• Fiscella K, Franks P. Vitamin D, race, and cardiovascular mortality: findings from a national US sample. Ann Fam Med. 2010 Jan-Feb;8(1):11-8. doi: 10.1370/afm.1035.
• Yanovich R, Friedman E, Milgrom R, Oberman B, Freedman L, Moran DS. Candidate gene analysis in israeli soldiers with stress fractures. J Sports Sci Med. 2012 Mar 1;11(1):147-55. eCollection 2012.
• Carlberg C. Genome-wide (over)view on the actions of vitamin D. Front Physiol. 2014 Apr 29;5:167. doi: 10.3389/fphys.2014.00167. eCollection 2014.
• Hossein-nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725. doi: 10.1371/journal.pone.0058725. Epub 2013 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): June 29, 2018
• Study Completion (Actual): June 29, 2018

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: vitamin D deficiency, genomics, vitamin D supplementation
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Musculoskeletal Diseases; Avitaminosis; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Vitamin D Deficiency; Rickets; Deficiency Diseases; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: HU001-15-1-TS05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No