Does Vitamin D Supplementation Enhance Resolution of Inflammation After Community-acquired Pneumonia? (ResolveD-CAP)
Primary Purpose
Pneumonia
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Vitamin D3 supplementation
Peripheral blood and induced sputum sampling
Chest computerised tomography (CT) scans
Symptom questionnaire
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Pneumonia focused on measuring convalescence, inflammation, resolution, vitamin D
Eligibility Criteria
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
Sites / Locations
- Barts Health NHS TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Immediate supplementation
Delayed supplementation
Arm Description
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
Placebo: oral placebo capsules once daily for 6 weeks Peripheral blood and induced sputum sampling Chest computerised tomography (CT) scans Symptom questionnaire
Outcomes
Primary Outcome Measures
Plasma IL-6 concentrations
IL-6
Secondary Outcome Measures
Serum CRP
CRP
Total white cell count and differential white cell count in induced sputum samples
WBC and differential counts
Immune cell phenotypes in peripheral blood
flow cytometry phenotypes, blood
Immune cell phenotypes in induced sputum samples
flow cytometry phenotypes, induced sputum
Plasma concentrations of pro- and anti-inflammatory mediators in peripheral blood
Cytokines, lipid mediators, blood
Plasma concentrations of pro- and anti-inflammatory mediators in induced sputum samples
Cytokines, lipid mediators, induced sputum
Plasma concentrations of pro- and anti-inflammatory mediators in supernatants from whole blood stimulated with antigens ex-vivo
Cytokines, lipid mediators, stimulated blood
Whole blood transcriptional profiles
mRNA
Volumes of lung abnormalities on chest CT imaging
CT data
Pneumonia symptom scores
CAP-Sym scores
Full Information
NCT ID
NCT02802722
First Posted
June 13, 2016
Last Updated
March 31, 2017
Sponsor
Queen Mary University of London
1. Study Identification
Unique Protocol Identification Number
NCT02802722
Brief Title
Does Vitamin D Supplementation Enhance Resolution of Inflammation After Community-acquired Pneumonia?
Acronym
ResolveD-CAP
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
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
February 24, 2017 (Actual)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Queen Mary University of London
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia
Keywords
convalescence, inflammation, resolution, vitamin D
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Immediate supplementation
Arm Type
Active Comparator
Arm Description
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
Arm Title
Delayed supplementation
Arm Type
Placebo Comparator
Arm Description
Placebo: oral placebo capsules once daily for 6 weeks Peripheral blood and induced sputum sampling Chest computerised tomography (CT) scans Symptom questionnaire
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3 supplementation
Other Intervention Name(s)
cholecalciferol, colecalciferol
Intervention Description
Capsules to be dispensed using an electronic dispenser to allow real time logging of adherence.
Intervention Type
Biological
Intervention Name(s)
Peripheral blood and induced sputum sampling
Intervention Description
To attain samples for immunological testing
Intervention Type
Radiation
Intervention Name(s)
Chest computerised tomography (CT) scans
Intervention Description
For volumetric quantification of lung abnormalities
Intervention Type
Other
Intervention Name(s)
Symptom questionnaire
Intervention Description
Symptom questionnaire for recent symptom history
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
To be dispensed using an electronic dispenser to allow real time logging of adherence.
Primary Outcome Measure Information:
Title
Plasma IL-6 concentrations
Description
IL-6
Time Frame
after 6 weeks of vitamin D3 supplementation
Secondary Outcome Measure Information:
Title
Serum CRP
Description
CRP
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Total white cell count and differential white cell count in induced sputum samples
Description
WBC and differential counts
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Immune cell phenotypes in peripheral blood
Description
flow cytometry phenotypes, blood
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Immune cell phenotypes in induced sputum samples
Description
flow cytometry phenotypes, induced sputum
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Plasma concentrations of pro- and anti-inflammatory mediators in peripheral blood
Description
Cytokines, lipid mediators, blood
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Plasma concentrations of pro- and anti-inflammatory mediators in induced sputum samples
Description
Cytokines, lipid mediators, induced sputum
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Plasma concentrations of pro- and anti-inflammatory mediators in supernatants from whole blood stimulated with antigens ex-vivo
Description
Cytokines, lipid mediators, stimulated blood
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Whole blood transcriptional profiles
Description
mRNA
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Volumes of lung abnormalities on chest CT imaging
Description
CT data
Time Frame
after 6 weeks of vitamin D3 supplementation
Title
Pneumonia symptom scores
Description
CAP-Sym scores
Time Frame
after 6 weeks of vitamin D3 supplementation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alicia D Yeap, MBBS
Phone
(44)7810715924
Email
a.d.yeap@qmul.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Martineau, MBBS
Organizational Affiliation
Queen Mary University of London
Official's Role
Study Chair
Facility Information:
Facility Name
Barts Health NHS Trust
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alicia Yeap, MBBS
Phone
+447810715924
Email
a.d.yeap@qmul.ac.uk
First Name & Middle Initial & Last Name & Degree
Alicia Yeap, MBBS
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18369199
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.
Results Reference
background
PubMed Identifier
22942205
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.
Results Reference
background
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Does Vitamin D Supplementation Enhance Resolution of Inflammation After Community-acquired Pneumonia?
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