To assess the PK/PD relationship of prednisolone regarding toxicity as clinical outcome in paediatric patients with autoimmune or autoinflammatory diseases.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to assess the association between
exposure (PK) and prednisolone toxicity (PD) in paediatric patients with
autoimmune or autoinflammatory diseases.
Secondary outcome
The secondary objectives of this study are:
- To assess information about occurrence and grade of toxicity in paediatric
patients with autoimmune or autoinflammatory diseases
- To identify determinants and its associated variability for development of a
population PK model
Background summary
The prevalence and incidence of autoimmune and autoinflammatory diseases have
been increasing in the past few years. One of the biggest concerns in
paediatric patients with systemic autoimmune and autoinflammatory diseases
remains the high prevalence of toxicity due to the long-term treatment with
systemic corticosteroids. The standard-of-care treatment of the majority of
onset autoimmune disorders in paediatric patients is high dose systemic
corticosteroids, like prednisolone. While systemic prednisolone have shown to
be highly effective in the treatment of autoimmune and autoinflammatory
diseases, the occurrence and severity of adverse events (AE) in patients
treated with prednisolone is substantial. Toxicity is often severe but highly
variable between patients and includes psychiatric and metabolic AE i.e.,
depression, personality and behavioural changes, sleep disturbances, excessive
weight gain, hypertension, diabetes mellitus, growth retardation and cushingoid
features. The association of pharmacokinetics (PK) of prednisolone and (level
of) toxicity has not yet been investigated in children. University Medical
Center (UMC) Utrecht has the unique facility of Liquid Chromatog-raphy-Mass
Spectrometry (LC-MS) which enables to measure PK in an extremely precise
manner. We hypothesize that precise dosing of prednisolone, with optimal
exposure in every individual patient, will decrease the incidence of AE in
paediatric patients with autoimmune and autoinflammatory diseases. Therefore,
we aim to investigate the PK in relation to toxicity (pharmacodynamics (PD)) of
prednisolone in children with autoimmune and autoinflammatory diseases.
Study objective
To assess the PK/PD relationship of prednisolone regarding toxicity as clinical
outcome in paediatric patients with autoimmune or autoinflammatory diseases.
Study design
This is a prospective observational study.
Study burden and risks
Patients will not have direct benefit from participating in this study. The
data obtained in this study will be used to assess the population PK and PD of
prednisolone in children with onset autoimmune and autoinflammatory diseases.
Burden will be minimal since for PK 4 (additional to standard of care) blood
samples of 2 ml will be drawn (limited sampling strategy). The volume of blood
that is drawn for the study does not exceed the recommended maximum. The
applied sampling strategy is minimally invasive, since all the patients that
are included are present during a routine outpatient clinic visit and will get
a peripheral cannula for the purpose of routine sampling and PK-sampling,
therefore there will be no extra blood punctures. Patients will be asked to
stay 4-5 hours for the PK-sampling and to fill in a questionnaire about
experiencing mental health AE. Patients will be asked to fill in 3
questionnaires in total.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
1. Patients treated by the WKZ with an autoimmune disease or autoinflammatory
disease including IBD;
2. Patients both newly diagnosed and with refractory or relapsed disease with
an indication for systemic prednisolon;
3. Planned to receive systemic prednisolone until at least one scheduled
follow-up visit between the 2nd and 6th week;
4. Informed consent form (ICF) signed prior to participation in the study.
Exclusion criteria
None in advance. However, according to expert opninion of the principal
investigator, any disease/circumstance that may influence the participation of
the potential subject in a negative way, will be excluded from participation in
this study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | https://onderzoekmetmensen.nl/nl/trial/51250 |
| CCMO | NL76235.041.21 |