Searching Patterns In the Robustness of Immunological FVIII Tolerance
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Hemophilia A, Hemophilia A, Congenital. Basic parameters: up to 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Netherlands
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Searching Patterns In the Robustness of Immunological FVIII Tolerance (SPIRIT)
Overview
Children with hemophilia A lack clotting factor VIII (FVIII) due to a genetic mutation. It is well known that administration of FVIII concentrate leads to immunological tolerance for the FVIII protein in the majority of children. In 30% of these children tolerance is not achieved leading to the development of anti-FVIII antibodies (i.e. inhibitors). Our knowledge on the underlying immunological mechanisms leading to tolerance is limited. Recently, Non-Factor Therapy (NFT) has become available for prevention of bleeding in patients with hemophilia, i.e. prophylaxis. Currently, many children with severe hemophilia A use NFT as the subcutaneous administration of NFT is very convenient. In children on NFT prophylaxis, intravenous FVIII concentrate is exclusively used on-demand for treatment of bleeding. As NFT is very effective in the prevention of bleeds, patients may not be exposed to the deficient FVIII protein for periods up to a year or longer. It is currently not known how robust immunological tolerance is in the absence of exposure to a deficient antigen. The infrequent exposure to FVIII, enabled by NFT, provides an opportunity to study the immunological tolerance mechanisms for FVIII in children with hemophilia A. The aim of SPIRIT is to investigate the mechanisms of the immunological tolerance to FVIII in patients with hemophilia A aged younger than 18 years using NFT for prophylaxis. In this observational cohort study, children (aged \<18 years) with congenital hemophilia A, who are treated with non-factor therapy as prophylaxis, will be longitudinally followed. Participants will have blood drawn anually, during the regular clinic visits, and additionally following FVIII exposure. Feces samples will be collected and analyzed in children aged \<12 years, following the same scheme as blood sampling. The main study endpoint are the immunological mechanisms underlying tolerance to FVIII, including presence, titers, subtypes and affinities of FVIII-specific (non-)neutralizing antibodies, FVIII-specific T and B cell responses and the role of gut microbiota.
Primary outcome measures
- FVIII-specific non-neutralizing antibody development [Time frame: From enrollment up to 5 years]
- Characterization of FVIII-specific antibodies (Immunoglobulin isotypes) [Time frame: From enrollment up to 5 years]
- Characterization of FVIII-specific antibodies (IgG subclasses) [Time frame: From enrollment up to 5 years]
- Characterization of FVIII-specific antibodies (affinity) [Time frame: From enrollment up to 5 years]
- Characterization of FVIII-specific antibodies (titer) [Time frame: From enrollment up to 5 years]
- FVIII inhibitor development (neutralizing antibodies) [Time frame: From enrollment up to 5 years]
Secondary outcome measures (3)
- FVIII-specific T and B cell responses [Time frame: From enrollment up to 5 years]
- Immunomodulatory microbial metabolites (in children <12 years) [Time frame: From enrollment up to 5 years]
- Gut microbiota composition (in children <12 years) [Time frame: From enrollment up to 5 years]
Eligibility criteria
Inclusion criteria
- Congenital hemophilia A of all severities
- Using NFT for prophylaxis
- Aged under 18 years
- Written informed consent
Exclusion criteria
- Acquired hemophilia A
- Any other bleeding disorder
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Netherlands · 1 center
- Amsterdam UMC, locatie AMC — Amsterdam
Identifiers
NCT: NCT07539402 · NL83658.018.23