Clinical Trial to Optimise Levels of Vitamin D for Rhinovirus Protection

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

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.

Study Overview

• Status: Unknown
• Conditions: Common Cold
• Intervention / Treatment: Other: Placebo; Dietary supplement: Vitamin D3; Dietary supplement: Vitamin D3

• Study Type: Interventional
• Enrollment (Anticipated): 195
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David A Jolliffe, PhD; Phone Number: 07920648370; Email: d.a.jolliffe@qmul.ac.uk
• Study Contact Backup: Name: Adrian R Martineau, PhD; Phone Number: 0207 882 2551; Email: a.martineau@qmul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1NY
    • St. Mary's Hospital
    • Contact: Sebastian L Johnston, PhD; Phone Number: 020 7594 3764; Email: s.johnston@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years
2. Gives written informed consent
3. Serum 25-hydroxyvitamin D concentration <75 nmol/L
4. Agrees not to take supplement containing vitamin D during participation
5. Agrees not to commence smoking or vaping during participation

Exclusion criteria:

1. Current smoker or vaper
2. Taken vitamin D supplement or other supplement containing vitamin D, in previous 3 months
3. Sunny holiday abroadI, defined as any location 51 degrees North/South of the equator, for ≥1 week, in the previous 3 months
4. Dependent(s) <6 months old
5. Positive serology for anti-RV16 antibodies
6. Living with someone with severe airways disease

7. Any of the following medical conditions:

   1. Diabetes mellitus
   2. Asthma
   3. Chronic Obstructive Pulmonary Disease
   4. Respiratory allergies
   5. Sarcoidosis
   6. Hyperparathyroidism
   7. Nephrolithiasis
   8. Active tuberculosis
   9. Liver failure
   10. Renal failure
   11. Lymphoma or other malignancy not in remission for ≥ 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: Imperial College London

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: March 26, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Rhinovirus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Picornaviridae Infections; Common Cold; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: COLDstudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified IPD will be shared with other researchers subject to terms of Data Transfer Agreement and IRB approval
• IPD Sharing Time Frame: 2 years after completion of the trial
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code

Drug and device information, study documents

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