Clinical trial NCT02954549: Vitamin D Supplementation in Warfighters
Official title: Genomics of Vitamin D Supplementation and Warfighter Nutritional Resilience
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D Deficiency Disease
Keywords: vitamin D deficiency, genomics, vitamin D supplementation
Lead sponsor: Madigan Army Medical Center
Sponsor class: FED
Collaborators: name: TriService Nursing Research Program
First posted: 2016-11-03
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 25(OH)D
timeFrame: 15 months
Secondary outcomes:
measure: Vitamin D gene expression
timeFrame: 3 months
Other outcomes:
Locations:
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
Study officials:
affiliation: Madigan Army Medical Center
name: Mary S McCarthy, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.