To evaluate whether supplementation of vitamin K2 decelerates the rate of mature cross-linked elastin degradation inpatients with COPD.
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the difference in the rate of elastin degradation after
8 weeks of vitamin K supplementation versus placebo (quantified by the plasma
desmosine assay).
Secondary outcome
Secondary endpoints are vitamin K-status after 8 weeks of treatment (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 and exacerbations during the study period. In
addition, we want to evaluate if different polymorphisms of the VKORC1 gene are
associated with desmosine and dp-ucMGP levels at baseline and after vitamin K2
supplementation.
Background summary
Elastin is a unique protein providing elasticity and resilience to dynamic
organs, such as lungs. Elastin is a basic requirement for both respiration and
circulation. The rate of elastin degradation is accelerated in COPD. Desmosine
(DES) is an amino acid that is only found in elastin fibers, and consequently,
plasma (p)DES levels 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. Elastin calcification
stimulates elastin degradation and vice versa. Elastin calcification is
inhibited by Matrix Gla Protein, which needs vitamin K to become activated.
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 patients with COPD
and controls with no lung disease. We hypothesized that improving vitamin
K-status by vitamin K2 supplementation would have a favorable decelerating
effect on elastin degradation.
Study objective
To evaluate whether supplementation of vitamin K2 decelerates the rate of
mature cross-linked elastin degradation in
patients with COPD.
Study design
Double-blind randomized placebo-controlled intervention trial.
Intervention
Randomisation: vitamin K2 or placebo.
Study burden and risks
Participating in the study has negligible risks as adverse side-effects from
vitamin K supplementation has never been described in persons who do not use
vitamin K antagonists.
Hornerheide 1
Horn 6085 NM
NL
Hornerheide 1
Horn 6085 NM
NL
Listed location countries
Age
Inclusion criteria
-Written informed consent
- Diagnosed with COPD based on post-bronchodilator FEV1/GVC <0.70 accordig to
the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.
-Ability to comply with all study requirements
- Age >40 years
Exclusion criteria
- Pregnant or lactating women, or subjects who intend to become pregnant within
the study period
-Subjects using vitamin K1 or K2 as supplements
-Active malignancy or cured malignancy <12 months prior to enrollment
-Use of vitamin K antagonists (acenocoumarol, fenprocoumon) in 12 months prior
to inclusion
- expectation of impaired gastro-intestinal uptake of vitamin K such as history
of (partial)bowel resection
-Serious mental impairment
-Exacerbation <2 weeks prior to enrolment
-Life expectation of less than 6 months on the basis of concurrent disease
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | Nederlands Trial Register: 7694 |
| CCMO | NL63985.068.18 |
| OMON | NL-OMON20264 |