Clonal Hematopoiesis and NETs Formation in Venous Thrombosis (CLODETTE) (CLODETTE)

March 20, 2025 updated by: University Hospital, Bordeaux

Role of Clonal Hematopoiesis and NETs Formation in Unusual Venous Thrombosis (CLODETTE)

Thrombo-embolic venous diseases are represented by deep venous thrombosis and/or pulmonary embolism. In some patients with repeated thrombosis or occurrence of thrombosis in unusual sites, the etiological workup remains negative, which represents a problem for the management of the anticoagulant treatments. Recently, two factors have been identified as important in the physiopathology of hemostasis and coagulation: the presence of clonal hematopoiesis of indetermined potential (CHIP) and the formation of neutrophil extracellular traps (NETs). In this study, these two factors will be studied in patients with repeated venous thrombosis or thrombosis occurring in unusual site.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

It has recently been shown that some patients clonal have mutations at a low level in hematopoietic cells (this phenomenon is named clonal hematopoiesis of indetermined potential (CHIP)) and that the presence of a clonal hematopoiesis is associated with an increased cardiovascular risk. However, few data exist about the implication of CHIP in venous thrombosis. Neutrophils extracellular traps are involved in the activation of hemostasis and coagulation. Murine models have highlighted the crucial role of NETs in the physiopathology of venous thrombosis. In patients, studies have demonstrated that NETs markers were present in arteries lesions as coronary plaques. However, few studies have analyzed the NETosis in the setting of venous thrombosis.

The study hypothesis is that patients with venous thrombosis may have an increased prevalence of CHIP and/or an increased NETosis formation, which may represent a predisposition for the occurrence of venous thrombosis. We also speculate that patients with CHIP may have an increased NETosis, due to the presence of activating clonal mutations in neutrophils.

Patients included will be : younger than 50-years-old with repeated thrombosis or thrombosis of unusual sites (cerebral venous thrombosis, splanchnic thrombosis) with a negative etiological workup and notably the absence of constitutional or acquired venous thrombosis risk factors. In this population, we will analyze the prevalence of CHIP and the NETosis via the study of 4 different NETosis plasmatic markers.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Not Applicable

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

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

6 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients (male or female) less than 50 y.o with :
  • Splanchnic venous territory thrombosis or
  • Cerebral venous thrombosis or
  • Venous thrombosis of the upper limb or
  • Pulmonary embolism (1st episode if male, 2nd episode if female) unprovoked or
  • 1 episode of deep vein thrombosis + 1 episode of arterial thrombosis

Exclusion Criteria:

  • Presence of a major or minor transient venous thrombosis risk factor:
  • Surgery within the last 3 months preceding the qualifying thrombotic episode
  • Lower limb fracture with immobilization > 3 days in the last 3 months preceding the qualifying thrombotic episode
  • Presence of estro-progestational contraception
  • Pregnancy
  • Immobilization for acute medical reasons within the last 3 months preceding the qualifying thrombotic episode
  • Air or car travel > 6 hours
  • Presence of a major or minor persistent risk factor for venous thrombosis:
  • Presence of active cancer (solid cancer or hematologic malignancy)
  • Chronic inflammatory digestive or joint diseases
  • Ongoing treatment with heparin (low molecular weight heparin (LMWH) or unfractionated heparin (UFH))
  • Presence of an abnormality on the thrombophilia test among the following abnormalities
  • Protein C deficiency
  • Protein S deficiency
  • Anti-thrombin deficiency
  • Heterozygous or homozygous factor II mutation
  • Heterozygous or homozygous factor V mutation
  • Presence of anti-phospholipid syndrome
  • Presence of myeloproliferative neoplasia
  • Presence of paroxysmal nocturnal hemoglobinuria

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of clonal hematopoiesis
Time Frame: At baseline
The existence of clonal hematopoiesis will be defined as the demonstration of at least one mutation in the blood cells of an apparently healthy subject (without obvious hematological pathology). DNA will be extracted from circulating leukocytes to search for mutations in a panel of 59 genes
At baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of one or more increased NETosis markers and/or a decreased NETosis-inhibiting marker (DNAse level) compared to a control population.
Time Frame: At baseline
Analysis of the following markers: MPO-DNA complex, Histone 3-DNA complex, citrullinated histone 3, DNAse
At baseline
Correlation (correlation coefficient values) between the presence of a CHIP and the formation of NETs
Time Frame: During final analysis
Correlation analysis will be performed between each NETosis marker and CHIP evaluation (presence or absence, number of mutations, variant allele frequency for each mutation)
During final analysis
Allele frequency
Time Frame: At baseline
Variant allele frequency of each detected mutation will be determined using NGS analysis
At baseline
Number of clonal mutations
Time Frame: At baseline
The number of clonal mutations for each patient will be determined using NGS analysis
At baseline
C-reactive protein (CRP) level as a marker of inflammation
Time Frame: At baseline
C-reactive protein concentration will be determined for each patient, as a marker of inflammation
At baseline
Site(s) of thrombosis
Time Frame: At baseline
Site(s) of thrombosis will be determined during examination of the patient
At baseline
Number of thrombosis
Time Frame: At baseline
The number of thrombosis will be determined during examination of the patient
At baseline

Collaborators and Investigators

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

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Alexandre GUY, University Hospital, Bordeaux

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)

March 3, 2023

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

January 24, 2023

First Submitted That Met QC Criteria

January 24, 2023

First Posted (Actual)

February 2, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 20, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2022/32

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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