Does Vitamin D Supplementation Enhance Resolution of Inflammation After Community-acquired Pneumonia? (ResolveD-CAP)

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Dietary supplement: Vitamin D3 supplementation; Biological: Peripheral blood and induced sputum sampling; Radiation: Chest computerised tomography (CT) scans; Other: Symptom questionnaire; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alicia D Yeap, MBBS; Phone Number: (44)7810715924; Email: a.d.yeap@qmul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate supplementation; 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; Capsules to be dispensed using an electronic dispenser to allow real time logging of adherence.; Other Names: cholecalciferol; colecalciferol; Biological: Peripheral blood and induced sputum sampling; To attain samples for immunological testing; Radiation: Chest computerised tomography (CT) scans; For volumetric quantification of lung abnormalities; Other: Symptom questionnaire; Symptom questionnaire for recent symptom history
Placebo Comparator: Delayed supplementation; 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; To attain samples for immunological testing; Radiation: Chest computerised tomography (CT) scans; For volumetric quantification of lung abnormalities; Other: Symptom questionnaire; Symptom questionnaire for recent symptom history; Other: Placebo; To be dispensed using an electronic dispenser to allow real time logging of adherence.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Investigators: Study Chair: Adrian Martineau, MBBS, Queen Mary University of London

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2017
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: June 15, 2016
• First Posted (Estimated): June 16, 2016

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: inflammation; vitamin D; convalescence; resolution
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Inflammation; Pneumonia; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 011280

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
• product manufactured in and exported from the U.S.: No