BILACO Trial: Biliary Atresia - a Severe Complex Congenital Liver Disease

NCT05399745 | Recruiting

• 1 other identifier: H-19042934
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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

Conditions

Biliary Atresia; Cognitive Impairment

Outcome Measures

Primary Outcomes (79)

• MRI of the brain

  % of patients with anatomic anomalies on MRI of the brain

  Inclusion

• Neurocognitive status: Early movement repertoire (General movement)

  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.

  Inclusion

• Neurocognitive status: Alberta Infant Motor Scale

  Neurocognitive test panel depending on age at inclusion: Alberta Infant Motor Scale if inclusion at diagnosis Percentile, highest is the best

  Inclusion

• Neurocognitive status: Bayley Scales of Development III

  Neurocognitive test panel depending on age at inclusion: Bayley Scales of Development III if inclusion up to 2.5 years: From 0-200, highest is best

  Inclusion

• Neurocognitive status: WIPPSI

  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

  Inclusion

• Neurocognitive status: ABC Movement

  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

  Inclusion

• Neurocognitive status: WISC-IV

  Neurocognitive test panel depending on age at inclusion: WISC-IV if inclusion between 6-16 years Wechsler Intelligence Scale for Children, 40 to 160, highest is best

  Inclusion

• Neurocognitive status: Auditory Verbal Learning Test/ToMaL

  Neurocognitive test panel depending on age at inclusion: Auditory Verbal Learning Test/ToMaL if inclusion between 6-18 years Mean 10 SD 3, highest is best

  Inclusion

• Neurocognitive status: TEA-Ch

  Neurocognitive test panel depending on age at inclusion: TEA-Ch if inclusion between 6-18 years Test of Everyday Attention for Children, normalized to z-score, highest is best

  Inclusion

• Neurocognitive status: BADS-C

  Neurocognitive test panel depending on age at inclusion: BADS-C if inclusion between 6-18 years Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best

  Inclusion

• Neurocognitive status: Test of Visual Perceptual Skills

  Neurocognitive test panel depending on age at inclusion: Test of Visual Perceptual Skills if inclusion between 6-18 years Percentile, highest is best

  Inclusion

• Neurocognitive status: CANTAB

  Neurocognitive test panel depending on age at inclusion: CANTAB if inclusion between 6-18 years Cambridge Neuropsychological Test Automated Battery

  Inclusion

• Neurocognitive status: The Beery Visuo-Motor Integration test

  Neurocognitive test panel depending on age at inclusion: The Beery Visuo-Motor Integration test if inclusion between 6-18 years Mean of 100 and standard deviation of 15, highest is best

  Inclusion

• Neurocognitive status: WAIS IV

  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

  Inclusion

• Neurocognitive status: Kiddie-sads

  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

  Inclusion

• Neurocognitive status: BRIEF 1

  Neurocognitive test panel depending on age at inclusion: BRIEF 1 if inclusion up to 6 years Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  Inclusion

• Neurocognitive status: BRIEF 2

  Neurocognitive test panel depending on age at inclusion: BRIEF 2 if inclusion between 6-18 years Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  Inclusion

• Neurocognitive status: CBCL

  Neurocognitive test panel depending on age at inclusion: CBCL if included between 2-18 years Child Behavior Checklist, percentile, lowest is best

  Inclusion

• Neurocognitive status: ADHD screening

  Neurocognitive test panel depending on age at inclusion: ADHD screening if included between 2-18 years Lowest is best, 0-78

  Inclusion

• Neurocognitive status: SRS-2

  Neurocognitive test panel depending on age at inclusion: SRS-2 screening if included between 6-18 years Social Responsiveness Scale, 32-114. lowest is best

  Inclusion

• Neurocognitive status: Vineland

  Neurocognitive test panel depending on age at inclusion: Vineland screening if included between 6-18 years Vineland Adaptive Behavior Scales, 20 to 160, highest is best

  Inclusion

• MRI of the brain

  % of patients with anatomic anomalies on MRI of the brain

  1 year

• Neurocognitive status: Alberta Infant Motor Scale

  Alberta Infant Motor Scale Percentile, highest is the best

  1 year

• Neurocognitive status: Bayley Scales of Development III

  Bayley Scales of Development III From 0-200, highest is best

  1 year

• Neurocognitive status: BRIEF 1

  BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  1 year

• Neurocognitive status: CBCL

  CBCL Child Behavior Checklist, percentile, lowest is best

  1 year

• Neurocognitive status: Kiddie-Sads

  Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best

  1 year

• MRI of the brain

  % of patients with anatomic anomalies on MRI of the brain

  2 years

• Neurocognitive status: Bayley Scales of Development III

  Bayley Scales of Development III From 0-200, highest is best

  2 years

• Neurocognitive status: BRIEF 1

  BRIEF 1 Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  2 years

• Neurocognitive status: CBCL

  CBCL Child Behavior Checklist, percentile, lowest is best

  2 years

• Neurocognitive status: Kiddie-Sads

  Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best

  2 years

• Neurocognitive status: ADHD

  ADHD Lowest is best, 0-78

  2 years

• Neurocognitive status: Vineland

  Vineland Adaptive Behavior Scales, 20 to 160, highest is best

  2 years

• MRI of the brain

  % of patients with anatomic anomalies on MRI of the brain

  6 years

• Neurocognitive: Movement ABC

  Neurocognitive test panel depending on age Movement Assessment Battery for Children, mean 10 SD 3, highest is best

  6 years

• Neurocognitive status: WISC-IV

  WISC-IV Wechsler Intelligence Scale for Children, 40 to 160, highest is best

  6 years

• Neurocognitive status: Auditory Verbal Learning Test/ToMaL

  Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best

  6 years

• Neurocognitive status: TEA-Ch

  TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best

  6 years

• Neurocognitive status: BADS-C

  BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best

  6 years

• Neurocognitive status: Test of Visual Perceptual Skills

  Test of Visual Perceptual Skills Percentile, highest is best

  6 years

• Neurocognitive status: The Beery Visuo-Motor Integration test

  The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best

  6 years

• Neurocognitive status: CANTAB

  CANTAB Cambridge Neuropsychological Test Automated Battery

  6 years

• Neurocognitive status: BRIEF 2

  BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  6 years

• Neurocognitive status: ADHD screening

  ADHD screening Lowest is best, 0-78

  6 years

• Neurocognitive status: SRS-2

  SRS-2 Social Responsiveness Scale, 32-114. lowest is best

  6 years

• Neurocognitive status: Kiddie-Sads

  Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best

  6 years

• Neurocognitive status: CBCL

  CBCL Child Behavior Checklist, percentile, lowest is best

  6 years

• Neurocognitive status: Vineland

  Vineland Vineland Adaptive Behavior Scales, 20 to 160, highest is best

  6 years

• MRI of the brain

  % of patients with anatomic anomalies on MRI of the brain

  11 years

• Neurocognitive status: Movement ABC

  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

  11 years

• Neurocognitive status: WISC-IV

  WISC-IV Wechsler Intelligence Scale for Children, 40 to 160, highest is best

  11 years

• Neurocognitive status: Auditory Verbal Learning Test/ToMaL

  Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best

  11 years

• Neurocognitive status:TEA-Ch

  TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best

  11 years

• Neurocognitive status: BADS-C

  BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best

  11 years

• Neurocognitive status: Test of Visual Perceptual Skills

  Test of Visual Perceptual Skills Percentile, highest is best

  11 years

• Neurocognitive status: The Beery Visuo-Motor Integration test

  The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best

  11 years

• Neurocognitive status: CANTAB

  CANTAB Cambridge Neuropsychological Test Automated Battery

  11 years

• Neurocognitive status: BRIEF 2

  BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  11 years

• Neurocognitive status: ADHD screening

  ADHD screening Lowest is best, 0-78

  11 years

• Neurocognitive status: SRS-2

  SRS-2 Social Responsiveness Scale, 32-114. lowest is best

  11 years

• Neurocognitive status: Kiddie-Sads

  Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best

  11 years

• Neurocognitive status: CBCL

  CBCL Child Behavior Checklist, percentile, lowest is best

  11 years

• Neurocognitive status: Vineland

  Vineland Adaptive Behavior Scales, 20 to 160, highest is best

  11 years

• MRI of the brain

  % of patients with anatomic anomalies on MRI of the brain

  16 years

• Neurocognitive status: Movement ABC

  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

  16 years

• Neurocognitive status: WISC-IV

  WISC-IV Wechsler Adult Intelligence Scale, 40-160, highest is best

  16 years

• Neurocognitive status: Auditory Verbal Learning Test/ToMaL

  Auditory Verbal Learning Test/ToMaL Mean 10 SD 3, highest is best

  16 years

• Neurocognitive status: TEA-Ch

  TEA-Ch Test of Everyday Attention for Children, normalized to z-score, highest is best

  16 years

• Neurocognitive status: BADS-C

  BADS-C Behavioural Assessment of the Dysexecutive Syndrome in Children, 0-24, mean 10 SD 3, highest is best

  16 years

• Neurocognitive status: Test of Visual Perceptual Skills

  Test of Visual Perceptual Skills Percentile, highest is best

  16 years

• Neurocognitive status: The Beery Visuo-Motor Integration test

  The Beery Visuo-Motor Integration test Mean of 100 and standard deviation of 15, highest is best

  16 years

• Neurocognitive status: CANTAB

  CANTAB Cambridge Neuropsychological Test Automated Battery

  16 years

• Neurocognitive status: BRIEF 2

  BRIEF 2 Behaviour Rating Inventory of Executive Function, percentile, lowest is best

  16 years

• Neurocognitive status: ADHD screening

  ADHD screening Lowest is best, 0-78

  16 years

• Neurocognitive status: SRS-2

  SRS-2 Social Responsiveness Scale, 32-114. lowest is best

  16 years

• Neurocognitive status: Kiddie-Sads

  Kiddie-Sads Kiddie Schedule for Affective Disorders and Schizophrenia, 0-61, lowest is best

  16 years

• Neurocognitive status: CBCL

  CBCL Child Behavior Checklist, percentile, lowest is best

  16 years

• Neurocognitive status: Vineland

  Vineland Adaptive Behavior Scales, 20 to 160, highest is best

  16 years

Secondary Outcomes (360)

• Genetics: Whole genome sequencing of blood

  Inclusion

• Genetics: Whole genome sequencing of liver biopsy

  Inclusion

• Microbiome: Urine proteomics

  Inclusion

• Microbiome: Feces proteomics

  Inclusion

• Microbiome: Saliva proteomics

  Inclusion

Study Arms (3)

Children with biliary atresia

Other: Neurocognitive monitoring

Children with Tetralogy of Fallot

Other: Neurocognitive monitoring

Healthy control children

Other: Neurocognitive monitoring

Interventions

Neurocognitive monitoring OTHER

Neurocognitive tests and MRI of the brain

Children with Tetralogy of Fallot; Children with biliary atresia; Healthy control children

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children with biliary atresia (BA), children with Tetralogy of Fallot (ToF) and healthy control children between the age of 0-17 years. The BA and ToF children were recruited from their respective outpatient clinics at Rigshospitalet, Denmark, which is the only centre treating these patients. Healthy controls were siblings to BA children, recruited from staffs children and friends or recruited from a general practitioners office in Nivaa, Denmark. The recruitment took place from March 2020 and is ongoing

You may qualify if:

• Biliary atresia
• Tetralogy of Fallot
• Healthy controls

You may not qualify if:

• \- Not able to participate in exams

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

MeSH Terms

Conditions

Biliary Atresia; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Vibeke Brix Christensen, MD, PhD, DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vibeke Brix Christensen, MD, PhD, DMSc

CONTACT

+4535458842; vibeke.brix.christensen@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, MD, PhD, DMSc, senior consultant

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: June 1, 2022
• Study Start: March 1, 2020
• Primary Completion (Estimated): December 31, 2039
• Study Completion (Estimated): December 31, 2040
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)