Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02624466 |
| Other study ID # |
UGent_UToPaed_1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 2015 |
| Est. completion date |
February 2019 |
Study information
| Verified date |
January 2023 |
| Source |
University Hospital, Ghent |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
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 this first part of UToPaed, 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). The toxins of which concentrations are best correlated with comorbidities
during the progress of CKD and eventually have representative kinetics (UToPaed - part 2:
Kinetic analysis) will be selected as markers. These markers will be, together with the
comorbidities, further tracked after interventions, i.e. starting on dialysis,
transplantation, changes in dialysis strategy (UToPaed - part 3 - intervention study).
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 a prospective observational multicenter study in children (≤ 18 years) with chronic
kidney disease (CKD) stage 2 to 5D with or without renal replacement therapy. In this study,
60 children with CKD stage 2 - 5 (without renal replacement therapy)(GROUP 1), 30 children
with CKD stage 5D treated with peritoneal dialysis (GROUP 2) and 30 children with CKD stage
5D treated with haemodialysis (GROUP 3) will be followed for a total duration of 24 months.
The study participants are evaluated on their standard visit at the outpatient clinic every 3
months. At this visit, a blood sample for uraemic toxin concentration is withdrawn and
several co-morbidities (growth, protein-energy wasting, cardiovascular disease, quality of
life, psychosocial functioning, sleep, attention and executive functions) are assessed.
Anthropometric parameters, dietary assessment, stool evaluation, nail evaluation, office and
24 hours ambulatory blood pressure monitoring, echocardiography and questionnaires are used
to map out the several co-morbidities.
Blood analyses are performed to get the concentrations of a wide variety of uraemic toxins:
i.e. small water soluble solutes, middle molecules and protein-bound solutes. All blood
analyses within this project are performed in the Ghent University Hospital: i.e. urea,
creatinine, calcium, and phosphorus are determined in the routine laboratory of the Ghent
University Hospital using standard methods, while all other uraemic toxins are determined in
the laboratory of the Nephrology Section using ELISA and (in-house developed) HPLC/UPLC
techniques. For the protein-bound solutes two runs are needed to distinguish between total
and free fractions of the protein-bound solutes.
The following actions are performed prior to enrolment:
- Review medical history to determine eligibility based on inclusion/exclusion criteria
- Obtain document consent from participant (>12 years) and parent/representative on study
consent form
- Schedule study visits for individuals who are eligible and available for the duration of
the study
- Provide potential participants with instructions needed to prepare for first study visit
Baseline visit:
- Verify inclusion/exclusion criteria.
- Obtain and record general patient information: age, sex, medical history, underlying
kidney disease, medication history, current medication chart, dialysis settings and
demographic information
- Assessment of dietary assessment by a skilled dietician by means of 3-day diet diary or
three 24-hours recall
- Perform clinical assessment including anthropometric parameters and office blood
pressure
- Perform a body composition monitoring (BCM) in children > 10 kg
- Collection of blood sample (all groups; EDTA immediately on ice; serum 15-30 minutes
rest and subsequently on ice), 24 hours urine sample (group 2; 24 hours prior to visit),
intradialytic urine sample (group 3) and 24 hours dialysate collection (group 2; 24
hours prior to visit) for determination of uraemic toxin concentration
Intermediate visits:
- Obtain general patient information: medication chart, changes in medical situation and
dialysis settings
- Assessment of dietary intake by a skilled dietician by means of 3-day diet diary or
three 24-hours recall every 3 months
- Perform clinical assessment including anthropometric parameters and office blood
pressure
- Perform BCM 3-monthly in children > 10 kg with renal replacement therapy (group 2 and 3)
and 1-yearly in children > 10 kg without renal replacement therapy (group 1)
- Collection of blood sample (group 1 to 3; EDTA immediately on ice; serum 15-30 minutes
rest and subsequently on ice), 24 hours urine sample (group 2 and 3; 24 hours prior to
visit) and 24 hours dialysate collection (group 2; 24 hours prior to visit) every 3
months for determination of uraemic toxin concentration.
- Collection of stool sample for determination of microbiota and metabolome 1-yearly (only
participants of Ghent University Hospital)
- Collection of nails for determination of carbamylation process every 6 months (only
participants of Ghent University Hospital)
- Perform echocardiography by a skilled paediatric cardiologist every year (visit 2, 5)
- Withdraw questionnaires from the parent and/or child assessing quality of life,
attention, sleep, executive function and parental functioning every 6 months (visit 2,
4, 6, 8)
- Perform 24 hours ambulatory blood pressure measurement in children > 6 years once a year
(visit 2, 5)
Final Study Visit:
- Obtain general patient information: medication chart, changes in medical situation and
dialysis settings (detailed overview appendix 2)
- Assessment of dietary assessment by a skilled dietician by means of 3-day diet diary or
three 24-hours recall
- Perform clinical assessment including anthropometric parameters and office blood
pressure
- Perform a body composition monitoring (BCM) in children > 10 kg
- Collection of blood sample (group 1 to 3; EDTA immediately on ice; serum 15-30 minutes
rest and subsequently on ice), 24 hours urine sample (group 2 and 3; 24 hours prior to
visit) and 24 hours dialysate collection (group 2; 24 hours prior to visit) for
determination of uraemic toxin concentration
- Perform echocardiography by a skilled paediatric cardiologist
- Perform 24 hours ambulatory blood pressure measurement in children > 6 years
The following socio-demographic questionnaires are asked to be completed:
1. Assessment of quality of life (QoL)
- PedsQL for children (5-18 years)
- PedsQL for children, disease specific (8-12 years, 13-18 years)
- Parent Proxy Report by parents (2-4 years, 5-7 years, 8-12 years, 13-18 years)
- Parent Proxy Report, disease specific by parents (8-12 years, 13-18 years)
2. Assessment of psychological wellbeing
- YSR for children (> 11 years)
- CBCL/TRF by parent/teachers (1,5-5 years, 6-18 years)
- CBSK for children (8-12 years), CBSA for children (13-18 years)
3. Assessment of attention & executive functions
- DBDRS by parents, teachers (6-16 years)
- BRIEF by parents/teachers (5-18 years)
4. Assessment of sleep
- ESS questionnaire by parents
- CSHQ questionnaire by parents
5. Assessment of family functioning
- PIP by parents
- HADS by parents
- PSI-S by parents
- PPS by parents
- CVS by parents
