BILACO Trial: Biliary Atresia - a Severe Complex Congenital Liver Disease
- Conditions
- Biliary AtresiaCognitive Impairment
- Interventions
- Other: Neurocognitive monitoring
- Registration Number
- NCT05399745
- Lead Sponsor
- Rigshospitalet, Denmark
- Brief Summary
Biliary atresia is the most severe form of cholestatic liver disease. The children have high morbidity and mortality and get devastating pruritus and fatigue, failure to thrive, progressive hepatic failure and impaired neurodevelopment. The etiology is mostly unknown. More than half need a new liver from a living or deceased donor during childhood. However, correct timing of the transplantation is extremely difficult because of lack of consensus based on clinical assessment tools. All though the incidence is low, the cost of this disease is tremendous from both a clinical and human perspective. So far, protocolized neurodevelopment tests, genetic profiling, precise malnutrition evaluation based on clinical appearance, biochemical markers and brain MRI-scans, body composition, immunological function, level of physical activity and optimal time of transplantation in cholestatic children are unknown.
The aim is to determine risk factors for neurocognitive impairment in children suffering from severe cholestasis in order to determine optimal time for liver transplantation from a brain perspective.
In a prospective study, the investigators will investigate risk factors related to brain-, heart-, gut- and immunological function in the Danish cohort. This cohort consists of 75 children aged 0-18 years. In addition, 30 aged and gender matched healthy and 20 tetra fallot children will serve as control groups. The children will undergo extensive and advanced liver function evaluation, genetic profiling, nutrition and immunological status, neuro-imaging and neurocognitive evaluation at time of diagnose, 2 years of age, pre-school, pre-teenage, and teenage. In case of a liver transplantation, additional neuro-cognitive tests will be performed
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Biliary atresia
- Tetralogy of Fallot
- Healthy controls
- Not able to participate in exams
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Children with Tetralogy of Fallot Neurocognitive monitoring - Healthy control children Neurocognitive monitoring - Children with biliary atresia Neurocognitive monitoring -
- Primary Outcome Measures
Name Time Method Neurocognitive status: ABC Movement Inclusion Neurocognitive test panel depending on age at inclusion:
ABC Movement if inclusion between 2.5-16 years
Movement Assessment Battery for Children, mean 10 SD 3, highest is bestNeurocognitive status: Test of Visual Perceptual Skills 16 years Test of Visual Perceptual Skills Percentile, highest is best
Neurocognitive status: CANTAB 16 years CANTAB Cambridge Neuropsychological Test Automated Battery
Neurocognitive status: WAIS IV Inclusion Neurocognitive test panel depending on age at inclusion:
WAIS IV if inclusion from 16 to 18 years Wechsler Adult Intelligence Scale, 40-160, highest is bestNeurocognitive: Movement ABC 6 years Neurocognitive test panel depending on age Movement Assessment Battery for Children, mean 10 SD 3, highest is best
Neurocognitive status: Bayley Scales of Development III 2 years Bayley Scales of Development III From 0-200, highest is best
Neurocognitive status: TEA-Ch 16 years TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best
Neurocognitive status: The Beery Visuo-Motor Integration test 16 years The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best
Neurocognitive status: CBCL 16 years CBCL Child Behavior Checklist, percentile, lowest is best
Neurocognitive status: Vineland 16 years Vineland Adaptive Behavior Scales, 20 to 160, highest is best
Neurocognitive status: Kiddie-Sads 16 years Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best
Neurocognitive status: Early movement repertoire (General movement) Inclusion Neurocognitive test panel depending on age at inclusion
% of patients with of abnormal movement assessed using early movement repertoire (GM) if inclusion at diagnosis. Early movement repertoire is a measurement tool where abnormal movement is identified.Neurocognitive status: Alberta Infant Motor Scale 1 year Alberta Infant Motor Scale Percentile, highest is the best
Neurocognitive status: WIPPSI Inclusion Neurocognitive test panel depending on age at inclusion:
WIPPSI if inclusion between 2.5-6 years:
Wechsler Preschool and Primary Scale of Intelligence, from 41 to 160, highest is bestNeurocognitive status: Auditory Verbal Learning Test/ToMaL 16 years Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best
Neurocognitive status: Kiddie-sads Inclusion Neurocognitive test panel depending on age at inclusion:
Kiddie-sads if included between 2-18 years Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is bestNeurocognitive status: ADHD 2 years ADHD Lowest is best, 0-78
MRI of the brain 16 years % of patients with anatomic anomalies on MRI of the brain
Neurocognitive status: BADS-C 16 years BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best
Neurocognitive status: BRIEF 1 2 years BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best
Neurocognitive status: BRIEF 2 16 years BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best
Neurocognitive status: ADHD screening 16 years ADHD screening Lowest is best, 0-78
Neurocognitive status: SRS-2 16 years SRS-2 Social Responsiveness Scale, 32-114. lowest is best
Neurocognitive status: WISC-IV 16 years WISC-IV Wechsler Adult Intelligence Scale, 40-160, highest is best
Neurocognitive status: Movement ABC 16 years Neurocognitive test panel depending on age at inclusion:
ABC Movement if inclusion between 2.5-16 years
Movement Assessment Battery for Children, mean 10 SD 3, highest is bestNeurocognitive status:TEA-Ch 11 years TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best
- Secondary Outcome Measures
Name Time Method Microbiome: Feces Next Generation Sequencing of microbial DNA 16 years Microbiome measurements on feces
Genetics: Whole genome sequencing of blood 16 years Whole genome sequencing of blood
Microbiome: Urine Next Generation Sequencing of microbial DNA 16 years Microbiome measurements on urine
Microbiome: Feces proteomics 16 years Microbiome measurements on feces
Microbiome: Saliva metabolomics 16 years Microbiome measurements on saliva
Microbiome: Urine metatranscriptomics 16 years Microbiome measurements on urine
prothrombin+proconvertin (PP) 16 years Standard liver evaluation
Genetics: Whole genome sequencing of liver biopsy 16 years Whole genome sequencing of liver biopsy
Microbiome: Feces metabolomics 16 years Microbiome measurements on feces
Status of the cardiac system: MRI of the lymph system 16 years % of patients with central lymph system anomaly
Status of the cardiac system: Near Infrared Fluorescence of the lymph system 16 years Near Infrared Fluorescence of the lymph system
Ultrasound of liver and bile ducts with elastography 16 years % of patients with liver fibrosis measured with ultrasound
FGF-19; Fibroblast growth factor 19 Inclusion Liver fibrosis status
GGT: Gamma-glutamyl transferase 16 years Standard liver evaluation
Alkaline phosphatase 16 years Standard liver evaluation
Clinical examination: Cirrhosis stigmata 16 years Incidence of palmar erythema
Anthropometry: Length 2 years cm
Microbiome: Saliva Next Generation Sequencing of microbial DNA 16 years Microbiome measurements on saliva
Level of Physical activity 16 years Accelerometer measurements
ELF-score: Enhanced Liver Fibrosis 16 years Liver fibrosis status
Anthropometry: Height 16 years cm
Meal stimulation measuring incretin 16 years Bile acid 16 years Fibroscan 16 years Liver stiffness (number)
PEDS-QL 16 years Pediatric Quality of Life Inventory Higher scores indicate better quality of life, from 0-100
Leptin 16 years Microbiome: Urine proteomics 16 years Microbiome measurements on urine
Microbiome: Saliva proteomics 16 years Microbiome measurements on saliva
Microbiome: Saliva metatranscriptomics 16 years Microbiome measurements on saliva
Status of the cardiac system: Ultrasound of the heart 16 years % of patients with anatomic anomalies on ultrasound of the heart
ALAT: alanine transaminase 16 years Standard liver evaluation
Bilirubin 16 years Standard liver evaluation
Essential fatty acids 16 years IGF-1 16 years Insulin-like growth factor 1
EDTA clearance 16 years Glomerular Filtration Rate Measured by 51 Cr-EDTA Clearance
Vaccination status 16 years Level of antibodies
Immunoresponse: Somatic hyper mutation 16 years Epstein-Barr Virus (EBV) 16 years level of EBV DNA present
Hepatobiliary scintigraphy 16 years Hepatic extraction fraction
Microbiome: Urine metabolomics 16 years Microbiome measurements on urine
Microbiome: Feces metatranscriptomics 16 years Microbiome measurements on feces
Liver biopsy 16 years Level of liver fibrosis (grade 0-4)
INR: international normalized ratio 16 years Standard liver evaluation
ASAT: Aspartate transaminase 16 years Standard liver evaluation
Thrombocytes 16 years Standard liver evaluation
Immunoresponse: RTE 16 years Recent thymic emigrants
Immunoresponse: Flow panel 16 years T-cell differentiation
Cytomegalovirus (CMV) 16 years level of CMV DNA present
MRI of liver and bile ducts with elastography 16 years Liver stiffness
Thymus scan with ultrasound 16 years Thymic index (measurement of size)
DEXA scan 16 years Dual energy x-ray absorptiometry
Ammonia 16 years Standard liver evaluation
FGF-19: Fibroblast growth factor 19 16 years Liver fibrosis status
Anthropometry: Weight 16 years kg
Anthropometry: Mid-upper arm circumference (MUAC) 16 years mm
Anthropometry: Head circumference 16 years cm
Autotaxin 16 years Immunoresponse: Immunoglobulin 16 years Indocyanine green clearance 16 years Fecal fat measurements 16 years
Trial Locations
- Locations (1)
Rigshospitalet
🇩🇰Copenhagen, Denmark