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

Primary Purpose

Venous Thromboses, Thromboembolic Disease, Neutrophil Extracellular Trap Formation

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Additional blood sampling
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Venous Thromboses focused on measuring Thrombosis, Venous thrombosis, Clonal hematopoiesis of indetermined potential

Eligibility Criteria

6 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de Bordeaux, Service de Neurologie
  • CHU de Bordeaux, Service Gastro-Entérologie
  • CHU de Bordeaux, Service Hématologie BiologiqueRecruiting
  • CHU de Bordeaux, Service Médecine Vasculaire
  • CHU de Bordeaux, Unité ambulatoire de Médecine VasculaireRecruiting

Outcomes

Primary Outcome Measures

Presence of clonal hematopoiesis
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

Secondary Outcome Measures

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

Full Information

First Posted
January 24, 2023
Last Updated
August 22, 2023
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT05711173
Brief Title
Clonal Hematopoiesis and NETs Formation in Venous Thrombosis (CLODETTE)
Acronym
CLODETTE
Official Title
Role of Clonal Hematopoiesis and NETs Formation in Unusual Venous Thrombosis (CLODETTE)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2023 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboses, Thromboembolic Disease, Neutrophil Extracellular Trap Formation, Clonal Hematopoiesis of Indeterminate Potential
Keywords
Thrombosis, Venous thrombosis, Clonal hematopoiesis of indetermined potential

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexandre GUY
Phone
0557656478
Email
alexandre.guy@chu-bordeaux.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Chloé JAMES
Phone
0557891979
Email
chloe.james@chu-bordeaux.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandre GUY
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Bordeaux, Service de Neurologie
City
Bordeaux
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Igor SIBON
Email
igor.sibon@chu-bordeaux.fr
Facility Name
CHU de Bordeaux, Service Gastro-Entérologie
City
Bordeaux
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victor DE-LEDINGHEN
Email
victor.deledinghen@chu-bordeaux.fr
Facility Name
CHU de Bordeaux, Service Hématologie Biologique
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandre GUY
Email
alexandre.guy@chu-bordeaux.fr
Facility Name
CHU de Bordeaux, Service Médecine Vasculaire
City
Bordeaux
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joël CONSTANS
Email
joel.constans@chu-bordeaux.fr
Facility Name
CHU de Bordeaux, Unité ambulatoire de Médecine Vasculaire
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophie SKOPINSKI
Email
sophie.skopinski@chu-bordeaux.fr

12. IPD Sharing Statement

Learn more about this trial

Clonal Hematopoiesis and NETs Formation in Venous Thrombosis (CLODETTE)

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