Clinical trial NCT02802722: Does Vitamin D Supplementation Enhance Resolution of Inflammation After Community-acquired Pneumonia?
Official title: A Prospective Randomised Placebo-controlled Study of the Influence of Vitamin D Supplementation on Resolution of Inflammation Following Community-acquired Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia
Keywords: convalescence
inflammation
resolution
vitamin D
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2016-06-16
Enrollment: 3
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Adults ≥50 years of age
2. Vitamin D deficiency at entry, defined as a serum total 25(OH)D concentration \<50 nmol/L
3. 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
4. Adequate mental capacity to give informed consent for participation in the study and gives written informed consent

Exclusion Criteria:

1. Currently taking any vitamin D supplementation
2. Known HIV infection, other condition causing immunosuppression, current immunosuppressive therapy or systemic corticosteroids
3. Known malignancy not in remission for \>3 years or terminal illness with prognosis \<1year
4. History of smoking within the previous 1 year
5. Known or suspected diagnosis of chronic obstructive pulmonary disease (COPD)
6. Previous hospitalisation within 10 days of admission
7. Aspiration pneumonia diagnosed by the clinical team
8. Known diagnosis of cystic fibrosis, bronchiectasis or interstitial lung disease at screening
9. Complications of pneumonia such as empyema or lung abscess at entry
10. Recent acute coronary syndrome within the previous 1 month
11. Long term oxygen therapy, chronic mechanical ventilation dependency or other contraindication to sputum induction
12. Serum corrected calcium concentration \>2.65 mmol/L at entry
13. Chronic kidney disease stage 4-5 (estimated glomerular filtration rate \<30ml/min) on an existing blood sample from the current hospital admission
14. Known clinical diagnosis of liver failure
15. Known or suspected diagnosis of active pulmonary tuberculosis
16. Known diagnosis of primary hyperparathyroidism
17. Known diagnosis of sarcoidosis
18. Known diagnosis of nephrolithiasis
19. Taking carbamazepine, phenytoin, phenobarbital, primidone, cardiac glycosides or benzothiadiazines with concomitant calcium supplementation at entry
20. Known allergy to vitamin D or its excipients
21. Currently taking part in another research study

Primary outcomes:
measure: Plasma IL-6 concentrations
timeFrame: after 6 weeks of vitamin D3 supplementation
Secondary outcomes:
measure: Serum CRP
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Total white cell count and differential white cell count in induced sputum samples
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Immune cell phenotypes in peripheral blood
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Immune cell phenotypes in induced sputum samples
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Plasma concentrations of pro- and anti-inflammatory mediators in peripheral blood
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Plasma concentrations of pro- and anti-inflammatory mediators in induced sputum samples
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Plasma concentrations of pro- and anti-inflammatory mediators in supernatants from whole blood stimulated with antigens ex-vivo
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Whole blood transcriptional profiles
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Volumes of lung abnormalities on chest CT imaging
timeFrame: after 6 weeks of vitamin D3 supplementation
measure: Pneumonia symptom scores
timeFrame: after 6 weeks of vitamin D3 supplementation
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts Health NHS Trust
Study officials:
affiliation: Queen Mary University of London
name: Adrian Martineau, MBBS
role: STUDY_CHAIR
References:
citation: Yende S, D'Angelo G, Kellum JA, Weissfeld L, Fine J, Welch RD, Kong L, Carter M, Angus DC; GenIMS Investigators. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1242-7. doi: 10.1164/rccm.200712-1777OC. Epub 2008 Mar 27.
citation: Remmelts HH, van de Garde EM, Meijvis SC, Peelen EL, Damoiseaux JG, Grutters JC, Biesma DH, Bos WJ, Rijkers GT. Addition of vitamin D status to prognostic scores improves the prediction of outcome in community-acquired pneumonia. Clin Infect Dis. 2012 Dec;55(11):1488-94. doi: 10.1093/cid/cis751. Epub 2012 Aug 31.