The aim of the FLOW project is to unravel immunological mechanisms driving inhibitor development in NSHA patients and HA carriers. We will focus on the association between (1) surgery , (2) intensive treatment, and (3) immunological biomarkers and…
ID
Source
Brief title
Condition
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the identification of:
1. Markers of an immune system prone for the development of inhibitors. ;
2. Markers of systemic inflammation that may indicate risk of an anti-FVIII
immune response, before inhibitors occur.
Determinants that will be assessed are subdivided in following categories: (1)
patient specific determinants (F8 gene mutation and other known genomic
predictors), (2) treatment specific determinants (reason for treatment,
intensity of treatment, occurrence of an infection) and (3) immunological
determinants (FVIII specific T and B cell responses, RNA expression profiles
and biomarkers).
Secondary outcome
Not applicable.
Background summary
Nonsevere hemophilia A (NSHA) is an inherited bleeding disorder, caused by a
mutation of the F8 gene, leading to a decrease of clotting factor VIII (FVIII)
levels to 1 * 40 International Units per deciliter (IU/dL). The development of
neutralizing FVIII antibodies (inhibitors) remains a major challenge in
hemophilia treatment with FVIII concentrate. Inhibitor development is
associated with a deterioration of clinical outcome, illustrated by an increase
in bleeding and mortality rate. F8 genotype is an important risk factor for
inhibitor development, and both surgical intervention and a high dose of FVIII
concentrate are associated with an increased inhibitor risk. Inhibitor
development has also been described in female hemophilia A (HA) carriers, who
received FVIII treatment for surgical procedures, resulting in a resembling
clinical picture as inhibitor NSHA patients, with increased bleeding tendency
and ineffectiveness of regular treatment strategies. Adequate prevention and
treatment of inhibitors in NSHA patients and HA carriers is limited by our lack
of understanding of the underlying immunological mechanisms. Elucidation of the
immunology driving inhibitor development is required to identify high-risk
patients and to understand the association between clinical risk factors and
inhibitor occurrence. It will furthermore give us the opportunity to develop
new preventive and therapeutic strategies.
Study objective
The aim of the FLOW project is to unravel immunological mechanisms driving
inhibitor development in NSHA patients and HA carriers. We will focus on the
association between (1) surgery , (2) intensive treatment, and (3)
immunological biomarkers and inhibitor development.
Study design
FLOW is a multicenter observational and translational cohort study.
Study burden and risks
The burden and risks of participation is the withdrawal of 5 blood samples in 6
months. A maximum of 36 mL will be drawn at each time point from adults and
children. For children younger than 12 years, who weigh less than 25 kg, lower
volumes will be used (Table 3 in C1 protocol). The blood sampling will be
combined as much as possible with regular outpatient department visits and
regular blood draws, in order to reduce the burden and additional visits to the
hospital. As this is the only intervention, 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
Nonsevere Hemophilia A patient or Hemophilia A carrier
Need for FVIII treatment for bleeding or surgery
Exclusion criteria
Use of immunosuppressive medication
Presence of immunological disease
Presence of FVIII inhibitors
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 | NL62743.018.17 |