Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02634775 |
| Other study ID # |
UGent_UToPaed_3 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 2015 |
| Est. completion date |
December 31, 2018 |
Study information
| Verified date |
August 2021 |
| Source |
University Hospital, Ghent |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Children with chronic kidney disease (CKD) suffer from one of the most devastating diseases
in childhood resulting in a lifelong need for health care, and a 3 times decreased life
expectancy. In addition, they have important comorbidities that negatively impact on their
quality of life and integration in society, jeopardizing their future even after a potential
transplantation. Retention of uraemic toxins is accepted to play a major role in the
pathogenesis of the comorbid conditions, but studies in children are lacking. Furthermore,
there are currently no good tools to evaluate severity and monitor adequacy of treatment,
resulting in suboptimal management.
The overall scientific objective of this four years UToPaed IWT-TBM project is to provide the
clinician with new diagnostic and therapeutic tools for the management of children with CKD,
based on the improved understanding of uraemic toxicity.
In UToPaed (part 1), the investigators will associate concentrations of a wide variety of
uraemic toxins with different comorbidities in CKD children, i.e. growth, protein-energy
wasting, quality of life, cardiovascular risk factors, circadian rhythm, sleep quality, and
psychosocial and neurocognitive functioning (i.e. cross-sectional and longitudinal). Those
toxins of which concentrations are best correlated with comorbidities during the progress of
CKD and those having representative kinetics (UToPaed - part 2: Kinetic analysis) will be
selected as markers. During this third part of UToPaed, these markers will be, together with
the comorbidities, further tracked after interventions, i.e. starting on dialysis,
transplantation, changes in dialysis strategy.
From the validated kinetic models (UToPaed - part 2 and 3), an open access user-friendly
prediction simulator (PAEDSIM) based on patient characteristics and marker concentrations
will be developed to optimise and individualise the dialysis therapy.
By providing clinicians with more advanced and appropriate tools to improve management of all
children with CKD, i.e. better assessment of the degree of renal dysfunction, better
determination of the ideal time to start renal replacement therapy, and more accurate
monitoring of dialysis adequacy, the investigators aim to improve neurocognitive and
psychosocial functioning (short term), growth, maturation into puberty, and social
integration (median term) and survival (long term).
Description:
This is an interventional multicenter study in children (≤ 18 years) with chronic kidney
disease (CKD) stage 2 to 5D with or without renal replacement therapy. They will be followed
for a total duration of 24 months.
Concentrations of the uraemic toxin markers and the different comorbidities will be followed
after an intervention. Some interventions will just happen in the treatment of the CKD child:
e.g. transplantation, start on dialysis, needed switch from PD to HD.
In the patients on PD, different approaches will be followed: more frequent exchanges
overnight, PET-directed dialysis regimes, adapted PD, using a mix of short, small volume
dwells, with longer, high volume dwells. These different strategies have so far only been
tested using the classic adequacy parameters urea and creatinine. The intervention is that
the children, as included in the longitudinal study, will be studied while on at least two
different PD strategies, serving as their own control, whereby the strategy will be linked
with the concentration of the uraemic toxin markers and comorbidities.
In the patients on HD, different dialysis strategies will be studied: conventional
haemodialysis 3x/week, daily haemodialysis, haemodiafiltration 3x/week, nocturnal 8h dialysis
3x/week, and the optimal dialysis regime as derived from the kinetic analysis (UToPaed_2).
The intervention is that the children, as included in the longitudinal study, will be studied
with at least 2 of the strategies, and that differences in plasma concentrations and removal
rate of the uraemic toxin markers will be measured. The measured predialysis concentrations,
time averaged concentrations (TACs), and total solute removal with the different strategies
will be compared to the results of the kinetic simulations in order to validate the
calibrated kinetic models of the uraemic toxin markers.
Based on the results, guidance on the most optimal dialysis strategy for each child will be
developed, and the child will consequently be treated on that modality during 1 year, to
allow evaluation of the longer term impact on quality of life, catch up growth, study results
and emergence of new comorbidities.
The therapeutic tool comprises an open access user-friendly prediction simulator, based on
the kinetics of the new markers (PAEDSIM) to simulate different dialysis strategies. With
different patient characteristics and uraemic toxin concentrations as input for the
simulation model, the program will derive the optimal dialysis strategy for the individual
patient striving for low predialysis concentrations and TACs.
The clinical use of these findings will be promoted by the organisation of a 'CKD Academy'
with workshops about the prediction simulator (PAEDSIM) and the related laboratory techniques
(see utilisation strategies).
