Natural History Study of ATP1A3-related Disease

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

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

Study Overview

• Status: Recruiting
• Conditions: Alternating Hemiplegia of Childhood; ATP1A3-related Disease; Rapid Onset Dystonia Parkinsonism; CAPOS
• Intervention / Treatment: Genetic: Whole exome sequencing

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Katerina Vezyroglou, MD; Phone Number: +44(0)20 7905 2980; Email: k.vezyroglou@ucl.ac.uk
• Study Contact Backup: Name: Helen Cross, PhD; Email: h.cross@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital
    • Contact: Aikaterini Vezyroglou, MD; Email: k.vezyroglou@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

UK-wide cohort of patients carrying an ATP1A3-mutation or diagnosed with a phenotype associated with ATP1A3-related disease.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease progression	1 year

Collaborators and Investigators

• Sponsor: Institute of Child Health
• Collaborators: University College, London; Great Ormond Street Hospital for Children NHS Foundation Trust
• Investigators: Principal Investigator: Helen Cross, PhD, UCL Institute of Child Health

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): August 31, 2023

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Dyskinesias; Paralysis; Hemiplegia; Dystonia; Parkinsonian Disorders
• Other Study ID Numbers: 17NC04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No