An observational study in Emphysema or COPD, Aneurysm and Cystic Fibrosis, sponsored by Canisius-Wilhelmina Hospital. Status unknown at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-01-25.
Sponsored by Canisius-Wilhelmina Hospital · Observational
Background: Elastin is a unique protein providing elasticity, resilience and deformability to dynamic tissues, such as lungs and vasculature. Elastin fibers are characterized by their high affinity for calcium. However, calcified elastin is more prone to the degrading effects of proteases and, in turn, partially degraded elastin has an even higher affinity for calcium. A disturbed balance between proteases and anti-proteases is a major underlying mechanism in the development of chronic obstructive pulmonary disease (COPD). Virtually the only protein that can protect elastin from calcification is matrix Gla-protein (MGP), which needs vitamin K for its activation. In COPD patients, a lower vitamin K status is found when compared to control subjects and an inverse association exists between vitamin K status and elastin degradation. In addition, vitamin K status is lower and elastin degradation is accelerated in Vitamin K antagonist (VKA) users.
VKAs are widely used. Nowadays, an increasing number of patients uses direct oral anticoagulants (DOACs), which do not influence vitamin K status. The hypothesis of this study is that discontinuation of VKAs results in an improved vitamin K status and deceleration of elastin degradation. In order to test this hypothesis, an observational pilot study will be conducted in which the change in elastin degradation- quantified by plasma desmosine concentrations - in patients who discontinue use of VKAs will be used as primary endpoint.
Study design: Observational study. Study population: A total of 30 VKA users who will discontinue the use of VKAs. Elastin degradation rate (quantified by plasma desmosine levels) and vitamin K status (quantified by measuring plasma levels of dephosphorylated uncarboxylated (dp-uc)MGP) will be measured during the use of VKAs and approximately 6 months after discontinuation of VKAs. Furthermore, the VKORC1 polymorphisms will be determined.
Main study parameters: The primary endpoint is the change in the rate of elastin degradation quantified by the plasma desmosine assay. Secondary endpoints are the change in vitamin K status quantified by measuring plasma levels of dp-ucMGP, the relation between desmosine and dp-ucMGP and differences of desmosine and dp-ucMGP levels among subjects with different polymorphisms of the vitamin K 2,3-epoxide reductase complex 1 (VKORC1) gene.
30 VKA users from the anticoagulant clinic in the Canisius Wilhelmina Hospital, who are going to discontinue the use of VKAs at short time
Exclusion Criteria:
* Approximately 6 months after discontinuation of VKAs one additional venipuncture will be performed for determination of dp-ucMGP and desmosine. * At baseline two additional blood collection tubes will be drawn for determination of dp-ucMGP, desmosine and VKORC1 polymorphisms. Since this is during one of the last regular International Normalized Ratio (INR) testing at the anticoagulation clinic, no additional venipuncture has to be performed at this moment.
Difference in elastin degradation rate
Difference in elastin degradation rate before and after discontinuation of VKAs, quantified by the change in plasma desmosine levels
Time frame: Plasma desmosine is measured at baseline and 6 months after discontinuation of VKAs
Difference in vitamin K status
Difference in vitamin K status before and after discontinuation of VKAs, quantified by the change in dp-ucMGP, discontinuation of VKAs.
Time frame: Plasma dp-ucMGP is measured at baseline and 6 months after discontinuation of VKAs
Association between desmosine and dp-ucMGP
Association between desmosine and dp-ucMGP both in patients who use VKAs and do not use VKAs.
Time frame: Desmosine and dp-ucMGP are determined before discontinuation of VKAs and 6 months after discontinuation of VKAs
Differences in desmosine and dp-ucMGP levels between different VKORC1 polymorphisms
Levels of dp-ucMGP and desmosine levels of subjects with different VKORC1 polymorphisms are compared, both during the use of VKAs and after discontinuation.
Time frame: Desmosine and dp-ucMGP are determined, both before discontinuation of VKAs and 6 months after discontinuation of VKAs. VKORC1 polymorphisms are determined before discontinuation of VKAs.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided
This study is status unknown, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Canisius-Wilhelmina Hospital