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Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS) (TAAS)

Primary Purpose

Glanzmann Thrombasthenia

Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Antibodies screening
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Glanzmann Thrombasthenia focused on measuring Glanzmann thrombasthenia, anti-GPIIb-IIIa immunization, MAIPA, Platelet transfusions, Recombinant activated factor VII

Eligibility Criteria

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

Inclusion Criteria:

  • All patients with a clear diagnosis of Glanzmann Thrombastenia (GT), whatever the subtype of disease.
  • Affiliated person or beneficiary of a social security scheme.
  • Free, informed and written consent signed by the participant, or parents or legal representant for the child population, and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

  • Current treatment that may interfere with anti-αIIbβ3 antibodies detection, such as intravenous immunoglobulins within the previous month.
  • Psychiatric, social or behavioral condition judged to be non-compatible with the respect of the protocol, including good observance of treatment and compliance to follow-up.
  • Adult protected by the law.

Sites / Locations

  • CHU Bordeaux - Hôpital Haut-Lévêque
  • CHU Bordeaux - Hôpital Pellegrin
  • Hôpital Bicêtre, APHP
  • CHU Limoges
  • Hôpital la Timone, APHM
  • CHU Nîmes
  • CHU Poitiers
  • CHU Strasbourg
  • CHU Toulouse

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with diagnosis of Glanzmann Thrombastenia (GT)

Arm Description

Antibodies screening will be systematically realized every six months (+/- 2 weeks) and after each last blood transfusion at 7-10 days and one month (+/- 2 weeks), during a period of 18 months

Outcomes

Primary Outcome Measures

Characterization of change of an anti-αIIbβ3 immunization
Characterization of change of an anti-αIIbβ3 immunization will be assessed with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)
Number of patients with positive anti-αIIbβ3 antibodies in relation to risk factors
Risk factors could be subtype of GT, year of birth, ITGA2B or ITGB3 gene mutation

Secondary Outcome Measures

Determination of the prevalence of anti-αIIbβ3 antibodies in a regional cohort of GT patients
Presence of anti-αIIbβ3 antibodies will be assessed with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)
Description of the kinetic of an anti-αIIbβ3 immunization following blood transfusion
Repetition of the antibodies measurements with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)
Determination of the mechanism of anti-αIIbβ3 antibodies blocking integrin function by determining the capacity of anti-αIIbβ3 antibodies to impair fibrinogen binding
In vitro studies will be performed by mixing serum of patients with washed donors' platelets and inhibition of the integrin will be studied by flow cytometry

Full Information

First Posted
August 17, 2020
Last Updated
August 3, 2023
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT04595617
Brief Title
Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS)
Acronym
TAAS
Official Title
Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 6, 2021 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2023 (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
This project aim to correlate risk factors (genetic, therapeutic and socio-demographic factors) to anti-αIIbβ3 antibodies formation following blood products transfusion (platelets or packed red cells) or pregnancy in a national cohort of GT patients.
Detailed Description
Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder caused by the absence or the dysfunction of the αIIbβ3 integrin, the most abundant receptor on platelets that mediates platelet aggregation through its binding of adhesive proteins. GT is readily identifiable by platelet function testing, and a lack of platelet aggregation in response to all physiological agonists is unique for this disease. The ITGA2B gene encodes for the αIIb subunit, whereas the ITGB3 gene encodes for β3. Mutations causing GT can affect either ITGA2B or ITGB3. The disease is characterized by spontaneous and trauma-related mucocutaneous bleeding, with variable expression ranging from easy bruising to fatal hemorrhages. Platelet transfusions are used to control or prevent life-threatening blood loss, but can become ineffective due to naturally occurring antibodies directed against αIIbβ3. Such antibodies are produced when patient's immune system comes into contact with normal αIIbβ3 expressing platelets. There is no currently consensus concerning the frequency, the long-term evolution, or the formation of characteristics of antibodies from GT patients in relation to the nature of the defective gene (ITGA2B or ITGB3), gene variations or other factors. Research are needed to confirm that nature of the gene defect may have a causative role in antibody development. Moreover, strength and persistence of antibodies may vary among patients with the same mutation, suggesting that other factors, such as immune modifiers genes, play a role in shaping antibody repertoire. Monoclonal antibody-specific immobilization of platelet antigens (MAIPA) is still considered as the reference method for evaluating the presence of anti-αIIbβ3 antibodies in GT patients. All the tests will be performed by the principal investigator site (Bordeaux).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glanzmann Thrombasthenia
Keywords
Glanzmann thrombasthenia, anti-GPIIb-IIIa immunization, MAIPA, Platelet transfusions, Recombinant activated factor VII

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Patients with diagnosis of Glanzmann Thrombastenia (GT)
Arm Type
Experimental
Arm Description
Antibodies screening will be systematically realized every six months (+/- 2 weeks) and after each last blood transfusion at 7-10 days and one month (+/- 2 weeks), during a period of 18 months
Intervention Type
Biological
Intervention Name(s)
Antibodies screening
Intervention Description
All included GT patients will be enrolled from different national centres during a 6 months period. Antibodies screening will be systematically realized every six months (+/- 2 weeks) and after each last blood transfusion at 7-10 days and one month (+/- 2 weeks), during a period of 18 months.
Primary Outcome Measure Information:
Title
Characterization of change of an anti-αIIbβ3 immunization
Description
Characterization of change of an anti-αIIbβ3 immunization will be assessed with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)
Time Frame
From inclusion to 18 months visit
Title
Number of patients with positive anti-αIIbβ3 antibodies in relation to risk factors
Description
Risk factors could be subtype of GT, year of birth, ITGA2B or ITGB3 gene mutation
Time Frame
From inclusion to 18 months visit
Secondary Outcome Measure Information:
Title
Determination of the prevalence of anti-αIIbβ3 antibodies in a regional cohort of GT patients
Description
Presence of anti-αIIbβ3 antibodies will be assessed with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)
Time Frame
From inclusion to 18 months visit
Title
Description of the kinetic of an anti-αIIbβ3 immunization following blood transfusion
Description
Repetition of the antibodies measurements with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)
Time Frame
At 7-10 days and 1 month (+/-2 weeks) after each blood transfusion
Title
Determination of the mechanism of anti-αIIbβ3 antibodies blocking integrin function by determining the capacity of anti-αIIbβ3 antibodies to impair fibrinogen binding
Description
In vitro studies will be performed by mixing serum of patients with washed donors' platelets and inhibition of the integrin will be studied by flow cytometry
Time Frame
through study completion, an average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients with a clear diagnosis of Glanzmann Thrombastenia (GT), whatever the subtype of disease. Affiliated person or beneficiary of a social security scheme. Free, informed and written consent signed by the participant, or parents or legal representant for the child population, and the investigator (at the latest on the day of inclusion and before any examination required by the research). Exclusion Criteria: Current treatment that may interfere with anti-αIIbβ3 antibodies detection, such as intravenous immunoglobulins within the previous month. Psychiatric, social or behavioral condition judged to be non-compatible with the respect of the protocol, including good observance of treatment and compliance to follow-up. Adult protected by the law.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathieu FIORE
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Bordeaux - Hôpital Haut-Lévêque
City
Bordeaux
Country
France
Facility Name
CHU Bordeaux - Hôpital Pellegrin
City
Bordeaux
Country
France
Facility Name
Hôpital Bicêtre, APHP
City
Le Kremlin-Bicêtre
Country
France
Facility Name
CHU Limoges
City
Limoges
Country
France
Facility Name
Hôpital la Timone, APHM
City
Marseille
Country
France
Facility Name
CHU Nîmes
City
Nîmes
Country
France
Facility Name
CHU Poitiers
City
Poitiers
Country
France
Facility Name
CHU Strasbourg
City
Strasbourg
Country
France
Facility Name
CHU Toulouse
City
Toulouse
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS)

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