IgG Dependent Monocyte Activation in Proximal Venous Thromboembolism (ActiMon)

The primary objective of this study is to search for, in vitro, elements associated with IgG-dependent monocyte activation (signaling pathway activation, expression of pro-coagulant and pro-inflammatory factors) and to describe their prevalence in female patients with a history of proximal venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) compared to control women.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism; Pulmonary Embolism
• Intervention / Treatment: Biological: Blood sampling

Detailed Description

The secondary objectives of this study include to compare the IgG-dependent monocyte activation profiles as a function of laboratory thrombophilia parameters. Essentially: Is IgG-dependent cell activation associated with the presence of anti-phospholipid antibodies (or their subtypes?), or do these profiles indicate something beyond the nosology of anti-phospholipid syndrome?

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

Study Locations

• France
  • Montpellier cedex 5, France, 34295
    • CHRU de Montpellier - Hôpital Saint-Eloi
  • Nîmes Cedex 09, France, 30029
    • CHRU de Nîmes - Hôpital Universitaire Carémeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patient population description: Patients will correspond to cases of proximal venous thromboembolism. They will be recruited during consultations conducted for the chronic management of a history of proximal venous thromboembolism or thrombophilia following a recent history of proximal venous thromboembolism. Venous thromboembolism, outside of acute phase episodes, has good symptom stability over time; no difference is to be expected between patients with a chronic history of proximal venous thromboembolism and new patients coming in for a checkup. Note that these patients may or may not have a history of placental vascular disease.

Healthy volunteer population description: This populations is composed of healthy, female, adult volunteers (<50 years in age) that have had at least 1 healthy pregnancy.

Description

Inclusion Criteria for patients:

• The patient has given her informed and signed consent
• The patient must be insured or beneficiary of a health insurance plan
• Adult woman 18 to 50 years old
• At least one prior incident of proximal venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) over three months ago regardless of the patient's history of placental vascular disease

Exclusion Criteria for patients:

• The patient is participating in another interventional study, or has participated in another interventional study within the past 3 months
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection, or is an adult under guardianship
• It is impossible to correctly inform the patient, or the patient refuses to sign the consent
• Postmenopausal women
• Pregnancy within the last 3 months
• Isolated history of superficial venous thrombosis
• Isolated history of distal venous thrombosis
• History of malignancy (solid or hematological)
• Known positive serology for hepatitis B
• Known positive serology for hepatitis C
• Known positive serology for human immunodeficiency virus (HIV)
• Episode of inflammatory or infectious disease dating back less than 3 months
• Impaired liver function characterized by liver enzymes (Alanine aminotransferase/ Aspartate aminotransferase) greater than 3 times normal
• Impaired renal function tests characterized by a glomerular filtration rate below 80 ml / min
• Drug background therapy (other than antiplatelet or anticoagulant therapy) used in the treatment of autoimmune disease

Inclusion Criteria for healthy volunteers:

• The healthy volunteer has given her informed and signed consent
• The healthy volunteer must be insured or beneficiary of a health insurance plan
• Adult woman 18 to 50 years old
• A history of at least one normal pregnancy defined by the birth of a child born alive in the absence of placental vascular complications

Exclusion Criteria for healthy volunteers:

• The healthy volunteer is participating in another interventional study, or has participated in another interventional study within the past 3 months
• The healthy volunteer is in an exclusion period determined by a previous study
• The healthy volunteer is under judicial protection, or is an adult under guardianship
• It is impossible to correctly inform the healthy volunteer, or the healthy volunteer refuses to sign the consent
• Postmenopausal women
• Pregnancy within the last 3 months
• History of superficial venous thrombosis
• History of distal venous thrombosis
• History of malignancy (solid or hematological)
• Known positive serology for hepatitis B
• Known positive serology for hepatitis C
• Known positive serology for human immunodeficiency virus (HIV)
• Episode of inflammatory or infectious disease dating back less than 3 months
• Impaired liver function characterized by liver enzymes (Alanine aminotransferase/ Aspartate aminotransferase) greater than 3 times normal
• Impaired renal function tests characterized by a glomerular filtration rate below 80 ml / min
• Background drug treatment
• History of proximal venous thromboembolism
• History of placental vascular disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with proximal VTE; Patients will correspond to cases of proximal venous thromboembolism. They will be recruited during consultations conducted for the chronic management of a history of proximal venous thromboembolism or thrombophilia following a recent history of proximal venous thromboembolism. Venous thromboembolism, outside of acute phase episodes, has good symptom stability over time; no difference is to be expected between patients with a chronic history of proximal venous thromboembolism and new patients coming in for a checkup. Note that these patients may or may not have a history of placental vascular disease. Intervention: Blood sampling	Biological: Blood sampling; Venous blood will be sampled for laboratory analyses (see outcomes).
Women with >1 healthy pregnancy; This populations is composed of healthy, female, adult volunteers (<50 years in age) that have had at least 1 healthy pregnancy. Intervention: Blood sampling	Biological: Blood sampling; Venous blood will be sampled for laboratory analyses (see outcomes).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The presence/absence of an activation profile	The following will be taken into account: Six signaling pathways (Protein kinase B, extracellular-signal-regulated kinases, Signal transducer and activator of transcription 5, P38 mitogen-activated protein kinases, Mechanistic Target Of Rapamycin, nuclear factor kappa-light-chain-enhancer of activated B cells), increases in the expression of tissue factor, and 5 pro-inflammatory factors (Intercellular Adhesion Molecule, tumor necrosis factor alpha, interferon gamma, Interleukin-1 beta, Interleukin 8). A pathway will be considered as "activated" or an expression profile as "increased" when the observed value is superior to the 95% confidence interval determined using healthy volunteer values. A patient is considered as having an activation profile if at least one of the above pathways or expressions is considered as activated / increased.	Day (0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
History of proximal deep vein thrombosis? yes/no		Day (0)
History of pulmonary embolism? yes/no		Day (0)
History of placental vascular pathology? yes/no		Day (0)
The presence / absence of antiphospholipid antibodies: lupus anticoagulant antibodies		Day (0)
The presence / absence of antiphospholipid antibodies: anti-cardiolipid antibodies		Day (0)
The presence / absence of antiphospholipid antibodies: anti-beta2-glycoprotein 1 antibodies		Day (0)
The presence / absence of a constitutional biological thrombophilia	The presence / absence of a constitutional biological thrombophilia (mutation of the Leiden V factor and the prothrombin gene, deficiency in physiological coagulation inhibitors)	Day (0)
Fibrin monomer (blood; mg/ L)		Day (0)
Blood D-dimers (ng/mL)		Day (0)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Sylvie Bouvier, MD, Centre Hospitalier Universitaire De Nimes

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2017
• Primary Completion (Actual): January 3, 2019
• Study Completion (Actual): June 23, 2020

Study Registration Dates

• First Submitted: March 15, 2016
• First Submitted That Met QC Criteria: March 17, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 29, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Proximal venous thromboembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism
• Other Study ID Numbers: AOI/2015/SB-01; 2016-A00447-44 (Other Identifier: RCB number)