title: Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol.
abstract: BACKGROUND
  Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients.
  
  
  METHODS
  We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate.
  
  
  CONCLUSIONS
  This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined.
  
  
  BACKGROUND
  This trial is registered in ClinicalTrials.gov, ID number NCT02122627 . Date of Registration April 2014.
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands. ra.rafiq@vumc.nl.
authors.forename: Rachida
authors.initials: R
authors.lastname: Rafiq
authors.affiliation: Department of Pulmonology, Radboud University Medical Center, Nijmegen, The Netherlands. floor.aleva@radboudumc.nl.|Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. floor.aleva@radboudumc.nl.
authors.forename: Floor E
authors.initials: FE
authors.lastname: Aleva
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. j.a.schrumpf@lumc.nl.
authors.forename: Jasmijn A
authors.initials: JA
authors.lastname: Schrumpf
authors.affiliation: Department of Pulmonology, Radboud University Medical Center, Nijmegen, The Netherlands. yvonne.heijdra@radboudumc.nl.
authors.forename: Yvonne F
authors.initials: YF
authors.lastname: Heijdra
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. c.taube@lumc.nl.
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.affiliation: Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands. j.daniels@vumc.nl.
authors.forename: Johannes Ma
authors.initials: JM
authors.lastname: Daniels
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands. p.lips@vumc.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands. pm.bet@vumc.nl.
authors.forename: Pierre M
authors.initials: PM
authors.lastname: Bet
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. p.s.hiemstra@lumc.nl.
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. andre.vanderven@lumc.nl.
authors.forename: André Jam
authors.initials: AJ
authors.lastname: van der Ven
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands. m.denheijer@vumc.nl.
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.affiliation: Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, The Netherlands. rt.dejongh@vumc.nl.
authors.forename: Renate T
authors.initials: RT
authors.lastname: de Jongh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002762:Cholecalciferol / Q000008:administration & dosage*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D018737:Hand Strength; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000188:drug therapy*
chemical_list: D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D