NCT04212195

Brief Summary

Wilson's disease (WD) is an inherited disorder that causes abnormal copper accumulation in the brain and/or liver. Some people develop neurological or psychiatric symptoms whereas other develop liver disease. The reasons for this are unclear but genetic factors are likely to contribute. Current treatment, using copper-binding medications, is required lifelong. Some respond well but others suffer debilitating side-effects or deteriorate despite treatment, leading to disability or the need for liver transplantation. In the first part of this study the main aim is to identify genetic factors that determine whether someone with a diagnosis of WD will develop neurological involvement or not. The investigators will invite 500 adults with WD across the UK to take part. Participants will be asked to complete an online questionnaire and provide a saliva sample for genetic testing using a collection kit sent via post. Identifying these genetic factors would significantly advance our understanding of the disease and may provide new targets for drug discovery or help guide more personalised approaches to treatment. In the second part of this study the main aim is to develop new ways to monitor the effect of WD on the brain using tests. Copper levels in blood and urine, currently used to monitor the disease, are unreliable and do not necessarily reflect ongoing brain damage. The role of MRI scans, cerebrospinal fluid tests or other measures of brain damage, commonly used in other neurological disorders, is unclear. The investigators will therefore follow a group of 40 patients using clinical assessments and a combination of neurological tests, including novel imaging and laboratory techniques, over 24 months. Developing new approaches to monitoring the effect of WD on the brain will enable better prevention of neurological disability and be essential for demonstrating the effectiveness of new treatments, such as gene therapy, in clinical trials in the future.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
500

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Dec 2018

Typical duration for all trials

Geographic Reach
1 country

11 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 6, 2018

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

December 18, 2019

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 26, 2019

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 6, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 6, 2021

Completed
Last Updated

December 26, 2019

Status Verified

December 1, 2019

Enrollment Period

3 years

First QC Date

December 18, 2019

Last Update Submit

December 23, 2019

Conditions

Keywords

Genetic modifiersBiomarkers

Outcome Measures

Primary Outcomes (2)

  • Clinical phenotype

    Responses to online questionnaires for the first part of the study will be used to the determine the presence or absence of neurological symptoms.

    Questionnaire responses will be collected over two years.

  • Unified Wilson's Disease Rating Scale (UWDRS)

    Participants in the second part of the study will be assessed at research visits using this scale (0-320)

    This assessment will be performed at two research visits 12-18 months apart.

Study Arms (2)

Part 1

Genetic determinants (n=500)

Genetic: Next generation sequencing

Part 2

Biomarker discovery (n=40)

Diagnostic Test: Imaging and fluid biomarkers

Interventions

Saliva samples

Part 1

Magnetic resonance imaging of the brain and urine, blood and cerebrospinal fluid sampling

Part 2

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Secondary care

You may qualify if:

  • Diagnosed with Wilson's disease
  • Age 16 years or over
  • Living in the UK

You may not qualify if:

  • Participant has another medical or psychiatric illness that would interfere in completing assessments
  • Participant is pregnant

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

RECRUITING

Cardiff and Vale University Health Board

Cardiff, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

National Hospital for Neurology and Neurosurgery

London, United Kingdom

RECRUITING

Royal Free London NHS Foundation Trust

London, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

RECRUITING

Salford Royal NHS Foundation Trust

Salford, United Kingdom

RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Saliva (part 1). Urine, blood and, in a subset, cerebrospinal fluid (part 2).

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

High-Throughput Nucleotide SequencingDiagnostic Imaging

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicMovement DisordersHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolism, Inborn ErrorsMetal Metabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sequence AnalysisGenetic TechniquesInvestigative TechniquesDiagnostic Techniques and ProceduresDiagnosis

Study Officials

  • Thomas Warner

    UCL Queen Square Institute of Neurology

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel Shribman

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 18, 2019

First Posted

December 26, 2019

Study Start

December 6, 2018

Primary Completion

December 6, 2021

Study Completion

December 6, 2021

Last Updated

December 26, 2019

Record last verified: 2019-12

Locations