Vitamin D and Immunity: Photosynthesis Versus Supplementation (IMMUNI-D)

The optimal way to restore serum 25-hydroxyvitamin D sufficiency is currently debatable. UV irradiation through sunshine exposure promotes endogenous vitamin D synthesis, although this can also be associated with a risk of UVR-induced skin cancer. Dietary supplements represent an alternative, which are increasingly being used in clinical trials to correct deficiency. However, it is unclear whether sunshine exposure and vitamin D supplementation induce comparable changes in immune function, or whether additional UVR-induced molecules may be responsible for proposed health benefits. Several studies report an inverse correlation between exposure to UVR and immune-mediated diseases, further supporting the theory that UVR may also be protective through non vitamin-D mediated pathways. So far it has been difficult to distinguish between immune-regulation by vitamin D and other mediators induced by UVR as the downstream effects are similar. A direct comparison of the biological effects of vitamin D obtained by UVR versus supplementation has never been made. This study aims to elucidate the differences in vitamin D generated by UVR exposure versus supplementation by comparing immunological endpoints

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency
• Intervention / Treatment: Radiation: UVR (Solar simulated radiation); Dietary supplement: Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18-40
• Fitzpatrick skin type I/II
• Healthy
• Serum 25(OH)D3 <50nmol/L

Exclusion Criteria:

Serum 25(OH)D3 >50nmol/L

• Pregnant or nursing women
• Women of child bearing age not using adequate contraception
• Are taking photosensitizing medication (i.e. causes you to be more sensitive to sunlight)
• Have had a history of skin disorders, sensitive skin, sensitivity to sunlight or skin cancer
• Have previously had an organ transplant
• Have partaken in a clinical study within the last 14 days
• Have had recent exposure to sunbeds (last 4 months) or holiday sun (including skiing)
• Are currently or have taken vitamin D supplements in the last 4 months Are asthmatic or suffer from any allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; No intervention
Experimental: UVR (Solar simulated radiation); Twice weekly 1.25 SED (sub-erythemal) (4 weeks)	Radiation: UVR (Solar simulated radiation); 1.25 SED Solar simulated radiation twice weekly
Experimental: Vitamin D3 supplementation; 4X 1000IU cholecalciferol tablets daily (28 days)	Dietary supplement: Vitamin D; Daily 4X 1000IU cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D status of healthy participants treated with oral vitamin D (cholecalciferol) or UVR (SSR) exposures and control (untreated)	Measure 25(OH)D3nmol/L via LC-MS/MS	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes to peripheral blood cell frequency	Frequency of major peripheral immune cells (e.g. CD3+ T cells, CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD19+ B cells, Natural Killer Cells, Classical, Non-classical and Intermediate Monocytes) in participants when vitamin D insufficient and sufficient. Via flow cytometry.	3 years
Impact upon the frequency and phenotype of peripheral blood dendritic cells	Frequency of peripheral blood dendritic cells (myeloid and plasmacytoid) in individuals with insufficient vitamin D levels and following vitamin D repletion via supplementation or UVR (SSR) exposures. Assessment of markers of maturation/tolerogenicity (MFI and frequency expressing) on myeloid and plasmacytoid dendritic cells direct ex vivo and after stimulation in vitro in participants when vitamin D insufficient and sufficient.	3 years
Gene expression in peripheral blood myeloid and plasmacytoid dendritic cells	Differentially regulated genes in myeloid and plasmacytoid dendritic cells in participants after vitamin D repletion via supplementation and UVR (SSR) exposure via Microarray.	3 years

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Investigators: Principal Investigator: Antony Young, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2015
• Primary Completion (Actual): April 14, 2017
• Study Completion (Actual): April 14, 2017

Study Registration Dates

• First Submitted: June 22, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 1, 2018
• Last Update Submitted That Met QC Criteria: July 25, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Vitamin D; Immune system; UVR
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: RJ115/N204

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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