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Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome (ACTION)

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ClinicalTrials.gov Identifier: NCT03912129
Recruitment Status : Not yet recruiting
First Posted : April 11, 2019
Last Update Posted : April 11, 2019
Sponsor:
Collaborator:
Institut des maladies génétiques, Paris
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
Characterization of the genetic causes, and of the immunopathological clinical and biological manifestations in children with pediatric Evans syndrome included in a prospective national observational cohort of rare diseases.

Condition or disease Intervention/treatment Phase
Evans Syndrome Genetic: blood sample Not Applicable

Detailed Description:

Pediatric Evans syndrome (pES) is a rare and severe disease combining immunologic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). French patients from the 30 hematologic pediatric centers are from 2004 included in a prospective national OBS'CEREVANCE cohort.

A first pilot study revealed a monogenic cause in 7/18 patients (40%) with mutations in the CTLA-4, LRBA, STAT3 GOF, and KRAS. TNGS or exome studies were performed between 2015 and 2018 inn 80 patients with pSE from the OBS'CEREVANCE cohort. This approach, combined with by immunophenotyping lymphocyte, identified a genetic cause of the disease in 26 patients (32%) (TNFRSF6, CTLA4, LRBA, STAT3 GOF, PIK3CD, RAG1, KRAS) and potential causal mutations in 18 other patients (22%), bringing the proportion of potential single gene cause to 76%.

The central hypothesis of this study is that most, if not all, cases of pSE are related to a monogenic or digenic cause, possibly with the intervention of genetic modifiers such as somatic mutations.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome
Estimated Study Start Date : May 6, 2019
Estimated Primary Completion Date : May 6, 2022
Estimated Study Completion Date : May 6, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
pediatric Evans Syndrome
Collection of biological samples of children with pSE included in the the OBS'CEREVANCE cohort and their parents, for genetic and functional immunological analyzes.
Genetic: blood sample

A first systematic approach by Targeted-Next Generation Sequencing will be used on the entire cohort of patients with pSE. This step will be performed on a sequencing chip specifically developed to detect anomalies in known genes involved in autoimmunity.

In patients for whom no mutations are identified, a whole exome sequencing (WES) approach will be applied to patients and their parents to seek to identify mutations in new genes that may be related to pSE.

In patients for whom this WES approach is unsuccessful, the search for somatic lymphocyte mutations, or copy number variants will be performed before considering a complete genome sequencing .

If several candidate genes are identified, the clinical data provided by the CEREVANCE and the phenotypic analyses carried out prior to genetic analyses by the CEDI laboratory will guide the choices to prioritize the study of the identified variants.





Primary Outcome Measures :
  1. Number of patients for whom a causal mutation has been identified (known or new) [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
  2. The number of biological samples collected for PSE children included in the OBS'CEREVANCE cohort and their relatives will be recorded [ Time Frame: every 3 months, between may 2019 and may 2022 ]

Secondary Outcome Measures :
  1. Immunopathological clinical manifestations [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
  2. Abnormalities of lymphocyte immunophenotyping [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
  3. The correlation between causal mutations identified with the clinical and immunological phenotype [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
  4. Physiopathological and potentially therapeutic classification of pES-T [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient registered in the French national prospective OBS'CEREVANCE cohort
  • Diagnosis of pediatric Evans syndrome (PTI+AHAI)
  • Age strictly under 18 years at the initial onset
  • Child residing in metropolitan France and affiliated to a french health insurance system
  • Free, informed, written and signed consent

Exclusion Criteria:

  • Evans syndrome secondary to chemotherapy, bone marrow transplantation or organ transplantation.
  • Refusal to participate from parents/patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03912129


Contacts
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Contact: Nathalie Aladjidi, M.D 05 57 82 02 79 nathalie.aladjidi@chu-bordeaux.fr
Contact: Aurore CAPELLI, PhD 05 57 82 08 77 aurore.capelli@chu-bordeaux.fr

Sponsors and Collaborators
University Hospital, Bordeaux
Institut des maladies génétiques, Paris

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03912129     History of Changes
Other Study ID Numbers: CHUBX 2018/49
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Bordeaux:
pediatric Evans Syndrome
genetic causes
immunophenotyping immunologic explorations

Additional relevant MeSH terms:
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Syndrome
Anemia, Hemolytic, Autoimmune
Thrombocytopenia
Disease
Pathologic Processes
Anemia, Hemolytic
Anemia
Hematologic Diseases
Autoimmune Diseases
Immune System Diseases
Blood Platelet Disorders