Prospective Descriptive Study of the Angiogenic T Cell Population in Subjects With Hereditary Hemorrhagic Telangiectasia (HHT)

NCT03572556 | Completed

• 1 other identifier: GUILHEM AMRO/AOI 2017
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary hemorrhagic telangiectasia (HHT) results from genetic deregulation of angiogenesis. It is characterized by mucocutaneous telangiectasia responsible for recurrent epistaxis affecting quality of life (anaemia, iron deficiency, social distress). More rarely, HHT is complicated by the appearance of pulmonary, hepatic or cerebral arteriovenous malformations that can lead to serious complications: cerebrovascular accidents, cerebral abscesses, high output heart failure, and massive hemoptysis (1). The intensity of symptoms increases with age but with significant individual variability, even for the same mutation in the same family. Thus, while the mutations responsible for the disease have been identified, the pathophysiology is not fully understood because these mutations do not explain the great diversity of clinical presentations. Other factors not yet identified probably play an important role. Angiogenic T cells (TANG) are a newly individualized T cell population, defined by a CD4+CXCR4+CD31+ phenotype, which plays a key role in differentiating endothelial progenitors (2). In an earlier study, the investigators showed that patients with HHT had a decrease in CD4+ and CD8+ LT compared to a cohort of healthy subjects (3). They hypothesize that the lymphopenia mainly involves TANG, whose quantification could make it possible to assess the individual level of angiogenesis during HHT. The evaluation of the TANG levels could thus make it possible to personalize HHT management.

Conditions

Hereditary Hemorrhagic Telangiectasia

Outcome Measures

Primary Outcomes (2)

• Average monthly duration (in minutes) of epistaxis over the 3 months following inclusion

  Through study completion, an average of 3 months

• Number/mm3 of circulating TANG (CD3+CXCR4+CD31+) at inclusion.

  At inclusion

Study Arms (2)

Patients

Hereditary hemorrhagic telangiectasia patients

Biological: Blood samples; Other: Epistaxis charts

Controls

Matched for age (+/- 5 ans) and sex.

Biological: Blood samples

Interventions

Blood samples BIOLOGICAL

* 5 mL dry tube to separate serum * Two 6 mL EDTA tubes for plasma separation * Eight 6 mL heparinized tubes for flow cytometry (quantification of TANG such as CD3+CD31+CXCR4+ and CEC) and quantification of angiogenesis markers.

Controls; Patients

Epistaxis charts OTHER

Three monthly epistaxis charts to be completed

Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

outpatient

You may qualify if:

• Person who has given consent
• Adult
• Person capable of understanding spoken and written French
• "Patient" group:
• Certain HHT (3 or 4 Curacao criteria - Appendix 2):
• Recurring epistaxis
• Telangiectasia of the skin or mouth
• Family hereditary context
• Arteriovenous visceral malformations
• Causal mutation identified
• Person capable of completing monthly epistaxis charts
• "Control" group :
• \- Control subjects will be matched to patients for age (+/- 6 years) and sex.

You may not qualify if:

• Person not affiliated to a national health insurance scheme
• Pregnant or breastfeeding woman
• Protected adult
• Hemoglobin levels less than 9 g/dl in the last 15 days
• Progressive or recent infectious disease, autoimmune disease or cancer (less than 6 months)
• Treatment in progress or stopped less than 6 months ago or to be introduced within the next 3 months of the following medications:
• bevacizumab
• tranexamic acid
• dipeptidyl peptidase 4 inhibitors (diabetic patient)
• beta-blockers (hypertensive patient)

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU Dijon Bourgogne

Dijon, 21079, France

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: June 28, 2018
• Study Start: June 28, 2018
• Primary Completion: March 9, 2020
• Study Completion: May 3, 2020
• Last Updated: November 20, 2020

Record last verified: 2019-11

Locations

FR (1)