Natural History Study of ATP1A3-related Disease
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|ClinicalTrials.gov Identifier: NCT03857607|
Recruitment Status : Active, not recruiting
First Posted : February 28, 2019
Last Update Posted : February 28, 2019
|Condition or disease||Intervention/treatment|
|ATP1A3-related Disease Alternating Hemiplegia of Childhood Rapid Onset Dystonia Parkinsonism CAPOS||Genetic: Whole exome sequencing Diagnostic Test: Broadband Near Infrared Spectroscopy (broadband-NIRS) Diagnostic Test: Transcranial Magnetic Stimulation (TMS)|
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. We believe that based on these scientific advances we 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|
|Estimated Enrollment :||100 participants|
|Official Title:||Natural History of ATP1A3-related Disease: a Deep Phenotyping-genotyping Project|
|Actual Study Start Date :||September 1, 2018|
|Estimated Primary Completion Date :||August 31, 2020|
|Estimated Study Completion Date :||August 31, 2022|
- 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.
- Diagnostic Test: Broadband Near Infrared Spectroscopy (broadband-NIRS)
A novel NIRS technology will be used to explore brain metabolism during paroxysmal events in ATP1A3-related disease
- Diagnostic Test: Transcranial Magnetic Stimulation (TMS)
TMS will be employed to explore motor cortex function in patients with ATP1A3-related disease.
- Disease progression [ Time Frame: 1 year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03857607
|Great Ormond Street Hospital|
|London, United Kingdom|
|Principal Investigator:||Helen Cross, PhD||UCL Institute of Child Health|