Natural History Study of ATP1A3-related Disease

NCT ID: NCT03857607

Last Updated: 2022-06-06

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2023-08-31

Brief Summary

An observational study aiming to study the natural history of a UK-wide patient cohort with ATP1A3-related disease.

Detailed Description

Alternating hemiplegia of childhood (AHC) is a rare very disabling neurodevelopmental syndrome caused by mutations in the gene ATP1A3. AHC is characterized by paroxysmal events including attacks of hemiplegia (weakness), dystonia (painful stiffening), oculomotor abnormalities and epileptic seizures. As the condition progresses permanent neurological symptoms, including unsteadiness and learning problems, emerge. Mutations in ATP1A3 also cause other related syndromes: rapid-onset dystonia-parkinsonism (RDP), less severe and usually presenting in adulthood, as well as cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome, a severe syndrome of early childhood.

Currently therapeutic options are very limited aiming at symptomatic relief with limited success. As ATP1A3-related syndromes are very rare diseases, with an estimated prevalence of about 1/1000000, randomised clinical trials of available therapies are not possible due to lack of a large enough patient cohort. However, the revolution in genetic diagnostics has made the identification of these patients and the correlation between their phenotypes possible. At the same time further novel technologies in neuromonitoring and neuroimaging, as well as videography and sleep monitoring have become available that could help us further examine and understand the underlying mechanisms especially of the paroxysmal episodes that characterise all ATP1A3-related syndromes. The investigators believe that based on these scientific advances they will be able to recruit a UK-wide patient cohort to conduct an in depth study of the progression of this disease.

This is particularly relevant at the moment as rapid progress in genetic therapies and other novel therapeutics makes the availability of new treatment options in the near future a realistic prospect and, even though we will most probably still not be able to identify a large enough cohort for randomised clinical trials, our natural history study will act as a much needed benchmark to which the success of novel treatments can be evaluated.

Conditions

ATP1A3-related Disease; Alternating Hemiplegia of Childhood; Rapid Onset Dystonia Parkinsonism; CAPOS

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Whole exome sequencing

Whole exome sequencing will be used to identify causative genes in ATP1A3 mutation negative patients, to confirm causality in ambiguous phenotypes and to identify modifier genes.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Children and adults of any age carrying a mutation in the ATP1A3-gene.
• Children and adults of any age matching an ATP1A3-related disease phenotype without a mutation in the gene.
• Written informed consent given by patient and/or parent/guardian.

Exclusion Criteria

• Patients with a phenotype not fitting ATP1A3-related disease and no mutation in the ATP1A3 gene.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: collaborator

Institute of Child Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helen Cross, PhD

Role: PRINCIPAL_INVESTIGATOR

UCL Institute of Child Health

Locations

Great Ormond Street Hospital

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Katerina Vezyroglou, MD

Role: CONTACT

k.vezyroglou@ucl.ac.uk

+44(0)20 7905 2980

Helen Cross, PhD

Role: CONTACT

h.cross@ucl.ac.uk

Facility Contacts

Aikaterini Vezyroglou, MD

Role: primary

k.vezyroglou@ucl.ac.uk

Other Identifiers

17NC04

Identifier Type: -

Identifier Source: org_study_id