Vitamin D Supplementation in Patients With COPD

Study Overview
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Brief Summary
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Vitamin D has an immunomodulatory role. the aim of the present study is to assess the effect of vitamin D supplementation on exacerbation rate of COPD patient with a vitamin D deficiency.

Detailed Description
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Rationale: Although vitamin D is well known for its function in calcium homeostasis and bone mineralisation, several studies have shown immunomodulatory effects of vitamin D. Vitamin D deficiency is a common problem in patients with COPD.. Objective: To assess the effect of vitamin D supplementation on exacerbation rate in patients with COPD and a vitamin D deficiency. Study design: Randomized, multi-center, double-blind, placebo-controlled intervention study. Study population: 240 patients aged 40 years and older with COPD and a vitamin D deficiency (25-hydroxyvitamin D concentration(25OHD)<50 nmol/l) with a COPD exacerbation. An exacerbation is defined as sustained worsening of respiratory symptoms during 48 hours and requiring oral corticosteroid, antibiotic or combination treatment that was initiated by a physician. Respiratory symptoms include at least one of the Anthonisen criteria (increased dyspnoea, sputum volume or purulence). Patients with a severe vitamin D deficiency (25OHD<15 nmol/l), known osteoporosis and/or use of vitamin D supplementation > 400 IU per day will be excluded. Intervention: Participants will be randomly allocated to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Main study parameters/endpoints: The primary endpoint is exacerbation rate. Follow-up of the study: Recruitment of participants is more troublesome than expected due to several reasons, more use of vitamin D supplements, higher 250hydroxyvitamin D levels than anticipated, less suitability due to presence other exclusion criteria. 29/8/2017 total number recruited participants is 119 10/7/2018 closure of recruitment, total number recruited participants is 158

Official Title
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Prevention of Exacerbations in Patients With COPD Through Vitamin D Supplementation: a Randomized Controlled Trial

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Vitamin D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent aged above 40 years GOLD stages II-IV and diagnosis COPD confirmed by a medical doctor. minimum of 10 packyears of smoking vitamin D deficiency (a serum 25-hydroxyvitamin D lower than 50 nmol/l) ability to comply with all study requirements Exclusion Criteria: pregnant or lactating women, or subjects who intend to become pregnant within the study period self-reported history of hypercalciemia or nephrolithiasis self-reported presence of sarcoidosis severe vitamin D deficiency (serum 25-hydroxyvitamin D lower than 15 nmol/l) life expectation of less than 6 months on the basis of concurrent disease interfering malignant diseases. diagnosed osteoporosis diagnosed asthma diagnosed chronic kidney disease stage 4 or higher (estimated glomerular filtration rate ≤ 29 ml/min/1,73 m2) serious mental impairment i.e. preventing to understand the study protocol or comply with the study aim; potentially unreliable patients and those judged by the investigator to be unsuitable for the study use of maintenance dose oral corticosteroids use of multivitamin supplement or vitamin D supplement which contains more than 400 IU per day current participation in a clinical rehabilitation programme

Ages Eligible for Study
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Minimum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>colecalciferol 16.800 IU per week | Drug: Vitamin D<br>* Colecalciferol 16.800 IU per week<br>* Other names: Colecalciferol, cholecalciferol, vitamin D3;|
| Placebo Comparator: Placebo<br>placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exacerbation rate | Definition of an exacerbation is according to the Anthonisen criteria | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first and second exacerbation | Time to first and second exacerbation | 1 year | 
| Time to first hospitalisation | Time to first hospitalisation | 1 year | 
| FEV1 | Forced Expiratory Volume in 1 sec | 1 year | 
| IC | Inspiratory capacity | 1 year | 
| FEV1/FVC | Forced expiratory volume in 1 sec/ forced vital capacity | 1 year | 
| FRC | Functional residual capacity | 1 year | 
| RV | Residual volume | 1 year | 
| TLC | Total lung capacity | 1 year | 
| MIP | Maximal inspiratory pressure | 1 year | 
| MEP | Maximal expiratory pressure | 1 year | 
| SMWT | Six-minute walk test | 1 year | 
| Chair stand test | Chair stand test | 1 year | 
| 3-meter walking test | 3-meter walking test | 1 year | 
| Tandem stand test | Tandem stand test | 1 year | 
| Total score physical function tests | The sum score of the physical function tests | 1 year | 
| Hand grip strength | Hand grip strength | 1 year | 
| Quality of life (SGRQ) | QoL by the St George respiratory questionnaire | 1 year | 
| Quality of life (SF12) | QoL by the 12 item short form survey | 1 year | 
| Anxiety (HADS) | Anxiety by the hospital anxiety and depression scale | 1 year | 
| Depression (CESD) | Depression by the center for epidemiologic studies depression scale | 1 year | 
| Quality of life (CCQ) | QoL by the Clinical COPD Questionnaire score | 1 year | 
| Concentrations of antimicrobial peptides and pro-inflammatory mediators in nasal secretions | AMPs in nasal secretions | 1 year | 
| Ex-vivo cytokine production capacity of peripheral blood mononuclear cells and immunophenotyping | cytokine production capacity by PBMCs | 1 year | 
| Typing of bacteria and viruses in nasal secretions | Typing of bacteria and viruses in nasal secretions | 1 year | 
| Use of corticosteroids | Use of corticosteroids | 1 year | 
| Use of antibiotics | Use of antibiotics | 1 year | 
| Physical activity (SQUASH) | physical activity by short questionnaire to assess health-enhancing physical activity | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, COPD, immunomodulation, pulmonary function