BILACO Trial: Biliary Atresia - a Severe Complex Congenital Liver Disease With High Mortality, Compromised Neurological Development, Severe Malnutrition and Unknown Etiology
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Neurocognitive status: ABC Movement
研究概览
简要总结
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
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Biliary atresia
- •Tetralogy of Fallot
- •Healthy controls
排除标准
- •Not able to participate in exams
结局指标
主要结局
Neurocognitive status: ABC Movement
时间窗: 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 best
Neurocognitive status: Test of Visual Perceptual Skills
时间窗: 16 years
Test of Visual Perceptual Skills Percentile, highest is best
Neurocognitive status: CANTAB
时间窗: 16 years
CANTAB Cambridge Neuropsychological Test Automated Battery
Neurocognitive status: WAIS IV
时间窗: 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 best
Neurocognitive: Movement ABC
时间窗: 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
时间窗: 2 years
Bayley Scales of Development III From 0-200, highest is best
Neurocognitive status: TEA-Ch
时间窗: 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
时间窗: 16 years
The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best
Neurocognitive status: CBCL
时间窗: 16 years
CBCL Child Behavior Checklist, percentile, lowest is best
Neurocognitive status: Vineland
时间窗: 16 years
Vineland Adaptive Behavior Scales, 20 to 160, highest is best
Neurocognitive status: Kiddie-Sads
时间窗: 16 years
Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best
Neurocognitive status: Early movement repertoire (General movement)
时间窗: 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
时间窗: 1 year
Alberta Infant Motor Scale Percentile, highest is the best
Neurocognitive status: WIPPSI
时间窗: 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 best
Neurocognitive status: Auditory Verbal Learning Test/ToMaL
时间窗: 16 years
Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best
Neurocognitive status: Kiddie-sads
时间窗: 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 best
Neurocognitive status: ADHD
时间窗: 2 years
ADHD Lowest is best, 0-78
MRI of the brain
时间窗: 16 years
% of patients with anatomic anomalies on MRI of the brain
Neurocognitive status: BADS-C
时间窗: 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
时间窗: 2 years
BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best
Neurocognitive status: BRIEF 2
时间窗: 16 years
BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best
Neurocognitive status: ADHD screening
时间窗: 16 years
ADHD screening Lowest is best, 0-78
Neurocognitive status: SRS-2
时间窗: 16 years
SRS-2 Social Responsiveness Scale, 32-114. lowest is best
Neurocognitive status: WISC-IV
时间窗: 16 years
WISC-IV Wechsler Adult Intelligence Scale, 40-160, highest is best
Neurocognitive status: Movement ABC
时间窗: 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 best
Neurocognitive status:TEA-Ch
时间窗: 11 years
TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best
次要结局
- GGT: Gamma-glutamyl transferase(16 years)
- Alkaline phosphatase(16 years)
- Clinical examination: Cirrhosis stigmata(16 years)
- Anthropometry: Length(2 years)
- Microbiome: Feces Next Generation Sequencing of microbial DNA(16 years)
- Microbiome: Urine Next Generation Sequencing of microbial DNA(16 years)
- Genetics: Whole genome sequencing of blood(16 years)
- Microbiome: Urine metatranscriptomics(16 years)
- Microbiome: Feces proteomics(16 years)
- Microbiome: Saliva metabolomics(16 years)
- prothrombin+proconvertin (PP)(16 years)
- Genetics: Whole genome sequencing of liver biopsy(16 years)
- Microbiome: Feces metabolomics(16 years)
- Status of the cardiac system: MRI of the lymph system(16 years)
- Status of the cardiac system: Near Infrared Fluorescence of the lymph system(16 years)
- Ultrasound of liver and bile ducts with elastography(16 years)
- FGF-19; Fibroblast growth factor 19(Inclusion)
- Microbiome: Saliva Next Generation Sequencing of microbial DNA(16 years)
- Level of Physical activity(16 years)
- ELF-score: Enhanced Liver Fibrosis(16 years)
- Anthropometry: Height(16 years)
- Meal stimulation measuring incretin(16 years)
- Bile acid(16 years)
- Fibroscan(16 years)
- PEDS-QL(16 years)
- Leptin(16 years)
- Microbiome: Urine proteomics(16 years)
- Microbiome: Saliva proteomics(16 years)
- Microbiome: Saliva metatranscriptomics(16 years)
- Status of the cardiac system: Ultrasound of the heart(16 years)
- ALAT: alanine transaminase(16 years)
- Bilirubin(16 years)
- Essential fatty acids(16 years)
- IGF-1(16 years)
- EDTA clearance(16 years)
- Vaccination status(16 years)
- Immunoresponse: Somatic hyper mutation(16 years)
- Epstein-Barr Virus (EBV)(16 years)
- Hepatobiliary scintigraphy(16 years)
- Microbiome: Urine metabolomics(16 years)
- Microbiome: Feces metatranscriptomics(16 years)
- Liver biopsy(16 years)
- INR: international normalized ratio(16 years)
- ASAT: Aspartate transaminase(16 years)
- Thrombocytes(16 years)
- Immunoresponse: RTE(16 years)
- Immunoresponse: Flow panel(16 years)
- Cytomegalovirus (CMV)(16 years)
- MRI of liver and bile ducts with elastography(16 years)
- Thymus scan with ultrasound(16 years)
- DEXA scan(16 years)
- Ammonia(16 years)
- FGF-19: Fibroblast growth factor 19(16 years)
- Anthropometry: Weight(16 years)
- Anthropometry: Mid-upper arm circumference (MUAC)(16 years)
- Anthropometry: Head circumference(16 years)
- Autotaxin(16 years)
- Immunoresponse: Immunoglobulin(16 years)
- Indocyanine green clearance(16 years)
- Fecal fat measurements(16 years)
研究者
Vibeke Brix Christensen
Principal investigator, MD, PhD, DMSc, senior consultant
Rigshospitalet, Denmark