Clinical Trial to Optimise Levels of Vitamin D for Rhinovirus Protection

Study Overview
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Brief Summary
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A phase II randomised, placebo-controlled trial to identify the optimal regimen of vitamin D supplementation for rhinovirus protection, determined by host responses to a clinically induced rhinovirus challenge. The primary outcome is rhinovirus titre after inoculation with rhinovirus; secondary outcomes are self-reported respiratory symptom scores, concentrations of cytokines and chemokines sampled from the nasal mucosa, and the transcriptional responses of nasal epithelial cells.

Official Title
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Clinical Trial to Optimise Levels of Vitamin D for Rhinovirus Protection (COLD)

Conditions
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Common Cold

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Dietary Supplement: Vitamin D3
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years Gives written informed consent Serum 25-hydroxyvitamin D concentration <75 nmol/L Agrees not to take supplement containing vitamin D during participation Agrees not to commence smoking or vaping during participation Exclusion criteria: Current smoker or vaper Taken vitamin D supplement or other supplement containing vitamin D, in previous 3 months Sunny holiday abroadI, defined as any location 51 degrees North/South of the equator, for ≥1 week, in the previous 3 months Dependent(s) <6 months old Positive serology for anti-RV16 antibodies Living with someone with severe airways disease Any of the following medical conditions: Diabetes mellitus Asthma Chronic Obstructive Pulmonary Disease Respiratory allergies Sarcoidosis Hyperparathyroidism Nephrolithiasis Active tuberculosis Liver failure Renal failure Lymphoma or other malignancy not in remission for ≥ 3 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Interventional Model Description: Two treatment arms of vitamin D3: low dose (800IU) vs. high dose (3,200IU) given daily, for 3 months
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Hypromellose capsules, given daily for 3 months<br>|
| Experimental: Low dose vitamin D3<br> | Dietary Supplement: Vitamin D3<br>* 800 IU Fultium-D3, cholecalciferol (Internis), given daily for 3 months<br>|
| Experimental: High dose vitamin D3<br> | Dietary Supplement: Vitamin D3<br>* 3,200 IU Fultium-D3, cholecalciferol (Internis), given daily for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rhinovirus titres | PCR-detected rhinovirus-16 load sampled from the nasal mucosa | +3 to +5 days after inoculation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory symptom score (Jackson Score) | Total self-reported respiratory symptom score (scored 0-32; increasing score equals increasing symptom severity) | +1 to +14 days after inoculation | 
| Cytokine and chemokine concentrations | Change in concentrations of inflammatory mediators (Including, but not limited to IL-1β, IL-2, IL-4, IL-5, Il-6, IL- 7, IL-8 [CXCL8], IL-10, IL-12, IL-13, IL-15, IL-17, IL-1RA, IL-2R, IFN-α, IFN-γ, TNF-α, MCP-1 [CCL2], MIP- 1α [CCL3], MIP-1β [CCL4], RANTES [CCL5], eotaxin [CCL11], MIG [CXCL9], IP-10 [CXCL10], EGF, FGF-basic, HGF, VEGF, G-CSF, GM-CSF) | Day 0 and +4 days after inoculation | 
| Change in level of vitamin D-regulated gene expression | Change in expression of DHCR7, CYP2R1, CYP3A4, CYP27A1, CYP27B1, CYP24A1, VDR, DBP, RXRA | Day 0 and +4 days after inoculation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rhinovirus