MedTrace Logo

The Effects of Discontinuation of Vitamin K Antagonists on the Rate of Elastin Degradation

NCT03285100 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 30

Last updated 2018-01-25

No results posted yet for this study

Summary

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.

Conditions

Interventions

DIAGNOSTIC_TEST

Venipuncture

* 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.

Sponsors & Collaborators

  • Maastricht University Medical Center

    collaborator OTHER

  • Canisius-Wilhelmina Hospital

    lead OTHER

Principal Investigators

  • Rob Janssen, MD, PhD · Canisius-Wilhelmina Hospital

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-10-31
Primary Completion
2018-10-01
Completion
2018-10-01

Countries

  • Netherlands

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03285100 on ClinicalTrials.gov