Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol

Rachida Rafiq, Floor E Aleva, Jasmijn A Schrumpf, Yvonne F Heijdra, Christian Taube, Johannes Ma Daniels, Paul Lips, Pierre M Bet, Pieter S Hiemstra, André Jam van der Ven, Martin den Heijer, Renate T de Jongh, Rachida Rafiq, Floor E Aleva, Jasmijn A Schrumpf, Yvonne F Heijdra, Christian Taube, Johannes Ma Daniels, Paul Lips, Pierre M Bet, Pieter S Hiemstra, André Jam van der Ven, Martin den Heijer, Renate T de Jongh

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/design: 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.

Discussion: 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.

Trial registration: This trial is registered in ClinicalTrials.gov, ID number NCT02122627 . Date of Registration April 2014.

Figures

Fig. 1
Fig. 1
Flowchart of study procedures during the PRECOVID trial. Randomisation will take place within 6-8 weeks after an exacerbation. During the study period of one year three study visits and four telephone contacts will take place. MIP: Maximal inspiratory pressure; MEP: Maximal expiratory pressure; TLC: Total lung capacity

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