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

January 23, 2018 updated by: Rob Janssen, Canisius-Wilhelmina Hospital

Pilot Study to Assess the Effects of Discontinuation of Vitamin K Antagonists on the Rate of Elastin Degradation

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6532SZ
        • Recruiting
        • Canisius Wilhelmina Hospital
        • Contact:
        • Principal Investigator:
          • Rob Janssen, MD, PhD
        • Principal Investigator:
          • Ianthe Piscaer, MD
        • Principal Investigator:
          • Ruben Zaal, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

30 VKA users from the anticoagulant clinic in the Canisius Wilhelmina Hospital, who are going to discontinue the use of VKAs at short time

Description

Inclusion Criteria:

  • Use of VKAs for at least 3 months
  • Stop VKAs at short time
  • Written informed consent
  • Age ≥18 years
  • Ability to comply with all study requirements

Exclusion Criteria:

  • Active malignancy or cured malignancy <12 months prior to enrollment
  • Use of maintenance dose oral corticosteroids
  • Serious mental impairment
  • Life expectation of less than 6 months on the basis of concurrent disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in elastin degradation rate
Time Frame: Plasma desmosine is measured at baseline and 6 months after discontinuation of VKAs
Difference in elastin degradation rate before and after discontinuation of VKAs, quantified by the change in plasma desmosine levels
Plasma desmosine is measured at baseline and 6 months after discontinuation of VKAs

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in vitamin K status
Time Frame: Plasma dp-ucMGP is measured at baseline and 6 months after discontinuation of VKAs
Difference in vitamin K status before and after discontinuation of VKAs, quantified by the change in dp-ucMGP, discontinuation of VKAs.
Plasma dp-ucMGP is measured at baseline and 6 months after discontinuation of VKAs
Association between desmosine and dp-ucMGP
Time Frame: Desmosine and dp-ucMGP are determined before discontinuation of VKAs and 6 months after discontinuation of VKAs
Association between desmosine and dp-ucMGP both in patients who use VKAs and do not use VKAs.
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
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.
Levels of dp-ucMGP and desmosine levels of subjects with different VKORC1 polymorphisms are compared, both during the use of VKAs and after discontinuation.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Canisius-Wilhelmina Hospital

Collaborators

Maastricht University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 31, 2017

Primary Completion (ANTICIPATED)

October 1, 2018

Study Completion (ANTICIPATED)

October 1, 2018

Study Registration Dates

First Submitted

September 13, 2017

First Submitted That Met QC Criteria

September 14, 2017

First Posted (ACTUAL)

September 15, 2017

Study Record Updates

Last Update Posted (ACTUAL)

January 25, 2018

Last Update Submitted That Met QC Criteria

January 23, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL60536.091.17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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