Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Vitamin D, COPD, immunomodulation, pulmonary function
Brief summary
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
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
Interventions
DRUGVitamin D
Colecalciferol 16.800 IU per week
DRUGPlacebo
Sponsors
Leiden University Medical Center
Radboud University Medical Center
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exacerbation rate | 1 year | Definition of an exacerbation is according to the Anthonisen criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first hospitalisation | 1 year | Time to first hospitalisation |
| FEV1 | 1 year | Forced Expiratory Volume in 1 sec |
| IC | 1 year | Inspiratory capacity |
| FEV1/FVC | 1 year | Forced expiratory volume in 1 sec/ forced vital capacity |
| FRC | 1 year | Functional residual capacity |
| RV | 1 year | Residual volume |
| TLC | 1 year | Total lung capacity |
| MIP | 1 year | Maximal inspiratory pressure |
| MEP | 1 year | Maximal expiratory pressure |
| SMWT | 1 year | Six-minute walk test |
| Chair stand test | 1 year | Chair stand test |
| 3-meter walking test | 1 year | 3-meter walking test |
| Tandem stand test | 1 year | Tandem stand test |
| Time to first and second exacerbation | 1 year | Time to first and second exacerbation |
| Hand grip strength | 1 year | Hand grip strength |
| Quality of life (SGRQ) | 1 year | QoL by the St George respiratory questionnaire |
| Quality of life (SF12) | 1 year | QoL by the 12 item short form survey |
| Anxiety (HADS) | 1 year | Anxiety by the hospital anxiety and depression scale |
| Depression (CESD) | 1 year | Depression by the center for epidemiologic studies depression scale |
| Quality of life (CCQ) | 1 year | QoL by the Clinical COPD Questionnaire score |
| Concentrations of antimicrobial peptides and pro-inflammatory mediators in nasal secretions | 1 year | AMPs in nasal secretions |
| Ex-vivo cytokine production capacity of peripheral blood mononuclear cells and immunophenotyping | 1 year | cytokine production capacity by PBMCs |
| Typing of bacteria and viruses in nasal secretions | 1 year | Typing of bacteria and viruses in nasal secretions |
| Use of corticosteroids | 1 year | Use of corticosteroids |
| Use of antibiotics | 1 year | Use of antibiotics |
| Physical activity (SQUASH) | 1 year | physical activity by short questionnaire to assess health-enhancing physical activity |
| Total score physical function tests | 1 year | The sum score of the physical function tests |
Countries
Netherlands
Outcome results
None listed