Randomized controlled trial to assess the effect of vitamin K supplementation on the rate of elastin degradation in COPD

INTERVENTION: Patients participating in a 8‐week inpatient rehabilitation program at CIRO+ will be randomized to receive either 360 mcg vitamin K2 or placebo orally once a day during 8 weeks. CONDITION: Chronic Obstructive Pulmonary Disease (COPD) PRIMARY OUTCOME: The primary endpoint is the difference in elastin degradation rate after the intervention between the active and placebo group. Elastin degradation rate is quantified by the change in plasma desmosine levels measured after 8 weeks. SECONDARY OUTCOME: Secondary endpoints are the changes in: vitamin K‐status (quantified by dp‐ucMGP), proteins induced by vitamin K abcense (PIVKA)‐II levels (inversely associated with vitamin K status), vitamin D levels, lung function parameters, questionnaires concerning psychosocial functioning/functional effects/health status, physical functioning, body composition, arterial stiffness and exacerbations during the study period. In addition, we will evaluate if different polymorphisms of the VKORC1 gene are associated with desmosine and dp‐ucMGP levels at baseline and after vitamin K2 supplementation. INCLUSION CRITERIA: ‐ Written informed consent ‐ Diagnosed with COPD based on post‐bronchodilator FEV1/FVC <0.70 according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria ‐ Participating in the inpatient rehabilitation program of rehabilitation center CIRO (Horn, The Netherlands) ‐ Ability to comply with all study requirements ‐ Age >40 years