Clinical trial NCT02122627: Vitamin D Supplementation in Patients With COPD
Official title: Prevention of Exacerbations in Patients With COPD Through Vitamin D Supplementation: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Vitamin D, COPD, immunomodulation, pulmonary function
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: Radboud University Medical Center
First posted: 2014-04-24
Enrollment: 158
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Exacerbation rate
timeFrame: 1 year
Secondary outcomes:
measure: Time to first and second exacerbation
timeFrame: 1 year
measure: Time to first hospitalisation
timeFrame: 1 year
measure: FEV1
timeFrame: 1 year
measure: IC
timeFrame: 1 year
measure: FEV1/FVC
timeFrame: 1 year
measure: FRC
timeFrame: 1 year
measure: RV
timeFrame: 1 year
measure: TLC
timeFrame: 1 year
measure: MIP
timeFrame: 1 year
measure: MEP
timeFrame: 1 year
measure: SMWT
timeFrame: 1 year
measure: Chair stand test
timeFrame: 1 year
measure: 3-meter walking test
timeFrame: 1 year
measure: Tandem stand test
timeFrame: 1 year
measure: Total score physical function tests
timeFrame: 1 year
measure: Hand grip strength
timeFrame: 1 year
measure: Quality of life (SGRQ)
timeFrame: 1 year
measure: Quality of life (SF12)
timeFrame: 1 year
measure: Anxiety (HADS)
timeFrame: 1 year
measure: Depression (CESD)
timeFrame: 1 year
measure: Quality of life (CCQ)
timeFrame: 1 year
measure: Concentrations of antimicrobial peptides and pro-inflammatory mediators in nasal secretions
timeFrame: 1 year
measure: Ex-vivo cytokine production capacity of peripheral blood mononuclear cells and immunophenotyping
timeFrame: 1 year
measure: Typing of bacteria and viruses in nasal secretions
timeFrame: 1 year
measure: Use of corticosteroids
timeFrame: 1 year
measure: Use of antibiotics
timeFrame: 1 year
measure: Physical activity (SQUASH)
timeFrame: 1 year
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Martin den Heijer, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rafiq R, Aleva FE, Schrumpf JA, Heijdra YF, Taube C, Daniels JM, Lips P, Bet PM, Hiemstra PS, van der Ven AJ, den Heijer M, de Jongh RT. Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol. BMC Pulm Med. 2015 Sep 23;15:106. doi: 10.1186/s12890-015-0101-4.
citation: Rafiq R, Aleva FE, Schrumpf JA, Daniels JM, Bet PM, Boersma WG, Bresser P, Spanbroek M, Lips P, van den Broek TJ, Keijser BJF, van der Ven AJAM, Hiemstra PS, den Heijer M, de Jongh RT; PRECOVID-study group. Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial. Am J Clin Nutr. 2022 Aug 4;116(2):491-499. doi: 10.1093/ajcn/nqac083.