Does Vitamin D Supplementation Enhance Resolution of Inflammation After Community-acquired Pneumonia?

Study Overview
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Brief Summary
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Previous research has shown that people who have been hospitalised for pneumonia are more likely to die of conditions such as heart attacks, stroke and cancer in the weeks to months after their illness. This risk is linked to raised levels of inflammation. Laboratory research shows that vitamin D can help to clear inflammation. Vitamin D deficiency is very common in the United Kingdom. The investigators are conducting this study to find out if taking vitamin D can hasten long-term recovery from pneumonia by reducing inflammation.

Official Title
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A Prospective Randomised Placebo-controlled Study of the Influence of Vitamin D Supplementation on Resolution of Inflammation Following Community-acquired Pneumonia

Conditions
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Pneumonia

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 supplementation
* Biological: Peripheral blood and induced sputum sampling
* Radiation: Chest computerised tomography (CT) scans
* Other: Symptom questionnaire
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥50 years of age Vitamin D deficiency at entry, defined as a serum total 25(OH)D concentration <50 nmol/L Admission to hospital with an acute illness (≤21 days) consistent with community-acquired pneumonia - at least one symptom of a lower respiratory tract infection (cough, sputum production, dyspnoea, wheeze, chest discomfort or pain, fever) and new infiltrate on chest radiograph Adequate mental capacity to give informed consent for participation in the study and gives written informed consent Exclusion Criteria: Currently taking any vitamin D supplementation Known HIV infection, other condition causing immunosuppression, current immunosuppressive therapy or systemic corticosteroids Known malignancy not in remission for >3 years or terminal illness with prognosis <1year History of smoking within the previous 1 year Known or suspected diagnosis of chronic obstructive pulmonary disease (COPD) Previous hospitalisation within 10 days of admission Aspiration pneumonia diagnosed by the clinical team Known diagnosis of cystic fibrosis, bronchiectasis or interstitial lung disease at screening Complications of pneumonia such as empyema or lung abscess at entry Recent acute coronary syndrome within the previous 1 month Long term oxygen therapy, chronic mechanical ventilation dependency or other contraindication to sputum induction Serum corrected calcium concentration >2.65 mmol/L at entry Chronic kidney disease stage 4-5 (estimated glomerular filtration rate <30ml/min) on an existing blood sample from the current hospital admission Known clinical diagnosis of liver failure Known or suspected diagnosis of active pulmonary tuberculosis Known diagnosis of primary hyperparathyroidism Known diagnosis of sarcoidosis Known diagnosis of nephrolithiasis Taking carbamazepine, phenytoin, phenobarbital, primidone, cardiac glycosides or benzothiadiazines with concomitant calcium supplementation at entry Known allergy to vitamin D or its excipients Currently taking part in another research study

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate supplementation<br>Dietary supplement: Vitamin D3 supplementation - oral capsules 6400 International Units once daily for 6 weeks Peripheral blood and induced sputum sampling Chest computerised tomography (CT) scans Symptom questionnaire | Dietary Supplement: Vitamin D3 supplementation<br>* Capsules to be dispensed using an electronic dispenser to allow real time logging of adherence.<br>* Other names: colecalciferol;Biological: Peripheral blood and induced sputum sampling<br>* To attain samples for immunological testing<br>Radiation: Chest computerised tomography (CT) scans<br>* For volumetric quantification of lung abnormalities<br>Other: Symptom questionnaire<br>* Symptom questionnaire for recent symptom history<br>|
| Placebo Comparator: Delayed supplementation<br>Placebo: oral placebo capsules once daily for 6 weeks Peripheral blood and induced sputum sampling Chest computerised tomography (CT) scans Symptom questionnaire | Biological: Peripheral blood and induced sputum sampling<br>* To attain samples for immunological testing<br>Radiation: Chest computerised tomography (CT) scans<br>* For volumetric quantification of lung abnormalities<br>Other: Symptom questionnaire<br>* Symptom questionnaire for recent symptom history<br>Other: Placebo<br>* To be dispensed using an electronic dispenser to allow real time logging of adherence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma IL-6 concentrations | IL-6 | after 6 weeks of vitamin D3 supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum CRP | CRP | after 6 weeks of vitamin D3 supplementation | 
| Total white cell count and differential white cell count in induced sputum samples | WBC and differential counts | after 6 weeks of vitamin D3 supplementation | 
| Immune cell phenotypes in peripheral blood | flow cytometry phenotypes, blood | after 6 weeks of vitamin D3 supplementation | 
| Immune cell phenotypes in induced sputum samples | flow cytometry phenotypes, induced sputum | after 6 weeks of vitamin D3 supplementation | 
| Plasma concentrations of pro- and anti-inflammatory mediators in peripheral blood | Cytokines, lipid mediators, blood | after 6 weeks of vitamin D3 supplementation | 
| Plasma concentrations of pro- and anti-inflammatory mediators in induced sputum samples | Cytokines, lipid mediators, induced sputum | after 6 weeks of vitamin D3 supplementation | 
| Plasma concentrations of pro- and anti-inflammatory mediators in supernatants from whole blood stimulated with antigens ex-vivo | Cytokines, lipid mediators, stimulated blood | after 6 weeks of vitamin D3 supplementation | 
| Whole blood transcriptional profiles | mRNA | after 6 weeks of vitamin D3 supplementation | 
| Volumes of lung abnormalities on chest CT imaging | CT data | after 6 weeks of vitamin D3 supplementation | 
| Pneumonia symptom scores | CAP-Sym scores | after 6 weeks of vitamin D3 supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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convalescence, inflammation, resolution, vitamin D