Clinical trial NCT04212195: Cohort Research on Wilson's Disease
Official title: Cohort Research On Wilson's Disease: Genetic Determinants and Biomarker Discovery for Neurological Involvement
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Wilson's Disease
Keywords: Genetic modifiers
Biomarkers
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2019-12-26
Enrollment: 500
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Secondary care

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.


Eligibility criteria: Inclusion Criteria (part 1 and part 2):

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

Exclusion Criteria (part 2):

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

Primary outcomes:
measure: Clinical phenotype
timeFrame: Questionnaire responses will be collected over two years.
measure: Unified Wilson's Disease Rating Scale (UWDRS)
timeFrame: This assessment will be performed at two research visits 12-18 months apart.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: UCL Queen Square Institute of Neurology
name: Thomas Warner
role: PRINCIPAL_INVESTIGATOR
References: