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

Hereditary Hemorrhagic Telangiectasia Clinical Trial

— TangRO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03572556
• Other study ID #: GUILHEM AMRO/AOI 2017
• Status: Completed
• Start date: June 28, 2018
• Est. completion date: May 3, 2020

Study information

• Verified date: November 2019
• Source: Centre Hospitalier Universitaire Dijon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 3, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)

• Immunosuppressive treatment in progress or recent (less than 6 months), including systemic steroid therapy. The use of inhaled or topical steroids is not an exclusion criterion.

• 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)

Related Conditions & MeSH terms

• Hereditary Hemorrhagic Telangiectasia
• Telangiectasia, Hereditary Hemorrhagic
• Telangiectasis

Intervention

Biological:
• Blood samples
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.

Other:
• Epistaxis charts
Three monthly epistaxis charts to be completed

Locations

Country	Name	City	State
France	CHU Dijon Bourgogne	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average monthly duration (in minutes) of epistaxis over the 3 months following inclusion		Through study completion, an average of 3 months
Primary	Number/mm3 of circulating TANG (CD3+CXCR4+CD31+) at inclusion.		At inclusion