Immunological Aspect of Thrombotic Thrombocytopenic Purpura (TTP)

NCT ID: NCT06945861

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 44 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-11
• Study Completion Date: 2027-05-11

Brief Summary

The general objective of the proposed project is to characterise phenotypically and functionally ADAMTS13-specific memory B lymphocytes and autoreactive T lymphocytes, in particular follicular helper T lymphocytes, in the acute phase of the disease, but also during its progression after treatment. The aim is to highlight their contribution to the initial pathogenic process, their evolution under treatment, and also their involvement in patients who are refractory to immunosuppressive therapies and during relapses. The aim of this project is to identify early phenotypic or functional parameters that are predictive of relapse and that can be used for personalised optimisation of treatment to maintain remission.

Detailed Description

Thrombotic thrombocytopenic purpura (TTP) is characterised by profound thrombocytopenia, haemolytic anaemia and organ dysfunction (cardiac, neurological or renal). The current treatment strategy includes plasma exchange, corticosteroid therapy, rituximab and caplacizumab, a bivalent humanised 'nanobody' targeting the A1 domain of factor Willebrand, thereby inhibiting platelet adhesion. Several response profiles to this first line of treatment have been observed: 1) durable remission profile (defined by the absence of thrombocytopenia, renal failure or clinical worsening for at least 30 days after the first day of normalisation of platelet levels), 2) refractory profile (defined by a platelet level after 4 days of intensive treatment of less than twice the initial level, associated with a persistently high level of lactate dehydrogenase), 3) relapse profile (defined by the recurrence of neurological manifestations, renal failure and/or thrombocytopenia < 100,000/mm3 for at least 2 days without any other cause identified after durable remission). The prognosis for TTP remains burdened by a mortality rate of around 10% and a relapse rate of 40-50%. The cellular players in the pathogenic process, responsible for the production of autoantibodies in this particularly severe disease, are still poorly characterised. This high-affinity memory B lymphocyte response requires cooperation with T lymphocyte players, namely follicular helper T lymphocytes. The involvement of these specific lymphocyte populations has been highlighted in the literature on other autoimmune diseases mediated by pathogenic autoantibodies, but has been little studied in TTP. The current high mortality rate in TTP suggests that a better understanding of immunopathological processes is required. Based on the model of other autoimmune diseases, this project should make it possible to identify the presence, at diagnosis, of circulating memory B lymphocytes specific for ADAMTS13, and also circulating autoreactive follicular helper T lymphocytes. After treatment with rituximab, depletion of circulating ADAMTS13-specific memory B lymphocytes is expected.

Conditions

Thrombotic Thrombocytopenic Purpura (TTP)

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1: patients in the acute phase of TTP

Consultation or hospitalisation when TTP is diagnosed, before treatment is initiated

No interventions assigned to this group

Groupe 2 : patient in durable remission with ADAMTS13 activity > 10%.

Follow-up consultation

No interventions assigned to this group

Groupe 3 : patient in remission with ADAMTS13 activity < 10%.

Follow-up consultation before initiation of pre-emptive treatment

No interventions assigned to this group

Group 4: relapsing patients

Consultation or hospitalisation at the time of relapse, before treatment is initiated

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• age over 18
• patients with TTP at any stage of diagnosis (acute phase, lasting remission or not, relapse)
• patients undergoing internal medicine at Rouen University Hospital
• people who have read and understood the information letter
• membership of a social security scheme

Exclusion Criteria

• a person deprived of liberty by an administrative or judicial decision or a person placed under court protection/guardianship or guardianship

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Rouen Hospital,

Rouen, , France

Site Status: RECRUITING

Countries

France

Central Contacts

David DM MALLET, Director

Role: CONTACT

david.mallet@chu-rouen.fr

02 32 88 82 65 ext. +33

Vincent VF FERRANTI, ARC

Role: CONTACT

vincent.ferranti@chu-rouen.fr

02 32 88 82 65 ext. +33

Facility Contacts

Mathilde ML LECLERCQ, Doctor

Role: primary

Mathilde.Leclercq@chu-rouen.fr

02 32 88 73 96 ext. +33

Other Identifiers

IDRCB : 2023-A00455-40

Identifier Type: OTHER

Identifier Source: secondary_id

2022/308/OB

Identifier Type: -

Identifier Source: org_study_id