Natural History Study of ATP1A3-related Disease

Alternating Hemiplegia of Childhood Clinical Trial

Official title:

Natural History of ATP1A3-related Disease: a Deep Phenotyping-genotyping Project

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03857607
• Other study ID #: 17NC04
• Status: Recruiting
• Start date: September 1, 2018
• Est. completion date: August 31, 2023

Study information

• Verified date: June 2022
• Source: Institute of Child Health
• Contact: Katerina Vezyroglou, MD
• Phone: +44(0)20 7905 2980
• Email: k.vezyroglou[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: August 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alternating Hemiplegia of Childhood
• ATP1A3-related Disease
• CAPOS
• Dystonia
• Hemiplegia
• Parkinsonian Disorders
• Rapid Onset Dystonia Parkinsonism

Intervention

Genetic:
• 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.

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Institute of Child Health	Great Ormond Street Hospital for Children NHS Foundation Trust, University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease progression		1 year