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ID
Source
Brief title
Health condition
COPD, chronic obstructive pulmonary disease.
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the difference in the rate of elastin degradation (quantified by the pDES assay) after 12 weeks of vitamin D/K vs. vitamin D/placebo supplementation.
Secondary outcome
Secondary endpoints (after 12 weeks of treatment) are: vitamin K-status (quantified by dp-ucMGP), vitamin D-status (quantified by 25(OH)D), questionnaires concerning health status and dyspnea level, and exacerbations during the study period.
Background summary
Elastin is a unique protein providing elasticity and resilience to dynamic organs, such as lungs and arteries. Elastin is a basic requirement for both respiration and circulation. The rate of elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD). Desmosine (DES) is an amino acid that is only found in elastin fibers, and plasma (p)DES levels consequently reflect the rate of elastin degradation. pDES is a strong predictor of mortality in COPD. We regard decelerating elastin degradation as an attractive novel therapeutic target in COPD. Vitamin D has anti-inflammatory properties, which might potentially have an attenuating effect on elastin degradation. However, we did not find a decreasing effect of vitamin D supplementation on pDES levels in a previous RCT, potentially due to an elastin calcifying effect of vitamin D. Elastin calcification stimulates elastin degradation and vice versa. Elastin calcification is inhibited by Matrix Gla Protein (MGP), a protein which needs vitamin K to become activated. Serum inactive levels of MGP, dephospho-uncarboxylated (dp-uc)MGP, are inversely associated with vitamin K status. Recently, we found significantly lower vitamin K status in COPD patients compared to controls. Furthermore, we found an inverse association between vitamin K-status and the rate of elastin degradation in both subjects with COPD and controls with no lung disease.
Study objective
We hypothesize that improving vitamin D and K-status by vitamin D3 plus K2 supplementation could have a favorable synergistic decelerating effect on elastin degradation.
Study design
14 weeks
Intervention
Patients are randomized between capsules of vitamin D3 plus vitamin K2 OR capsules of vitamin D3 plus capsule placebo (12 weeks).
Inclusion criteria
Diagnosed with COPD based on post-bronchodilator FEV1/FVC <0.70 according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.
Serum 25(OH)D<50 nmol/L
Age ≥40 and ≤75 years at screening visit
Exclusion criteria
Subjects using vitamin K as supplements <3 months prior to the screening visit
Use of vitamin K antagonists (i.e acenocoumarol, fenprocoumon) in 12 months prior to the screening visit
Exacerbation <6 weeks prior to the screening visit
Use of digoxin and/or thiazide diuretics
Hypercalcemia (i.e. corrected calcium for albumin >2.8 mmol/L)
Kidney stones in medical history
Severe renal failure (i.e. eGFR < 30 ml/min/1.73 m2)
Hyperparathyroidism
Design
Recruitment
IPD sharing statement
Plan description
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7771 |
| Other | CMO Regio Arnhem-Nijmegen : 2019-5482 / NL70120.091.19 |