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.
ID
Source
Brief title
Condition
- Haematological disorders NEC
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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
immunomodulatory microbial metabolites in the fecal samples (i.e. short chain
fatty acids, incl. butyrate and/or tryptophan catabolites).
Secondary outcome
N.A.
Background summary
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.
Study objective
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.
Study design
SPIRIT is a multicentre observational cohort study.
Study burden and risks
The burden and risks of participation is the withdrawal of extra blood samples
in the follow-up period of the study. A maximum of 30 mL blood will be drawn at
each time point (i.e. annually or after FVIII exposure). For children who weigh
less than 20 kg, lower volumes will be used. The blood sampling will be
combined as much as possible with regular outpatient department visits and
regular blood draws. As it is an observational study, the risk of participating
in this study for the patient is negligible.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Congenital hemophilia A of all severities
Using Non-factor therapy
Aged under 18 years
Written informed consent
Exclusion criteria
Acquired hemophilia A
Any other bleeding disorder
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83658.018.23 |