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Trial record 1 of 4 for:    ATP1A3
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Natural History Study of ATP1A3-related Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03857607
Recruitment Status : Active, not recruiting
First Posted : February 28, 2019
Last Update Posted : February 28, 2019
Great Ormond Street Hospital for Children NHS Foundation Trust
University College, London
Information provided by (Responsible Party):
Institute of Child Health

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

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)

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. 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.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Intervention Details:
  • 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.

Primary Outcome Measures :
  1. Disease progression [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03857607

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United Kingdom
Great Ormond Street Hospital
London, United Kingdom
Sponsors and Collaborators
Institute of Child Health
Great Ormond Street Hospital for Children NHS Foundation Trust
University College, London
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Principal Investigator: Helen Cross, PhD UCL Institute of Child Health

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Responsible Party: Institute of Child Health Identifier: NCT03857607     History of Changes
Other Study ID Numbers: 17NC04
First Posted: February 28, 2019    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Parkinsonian Disorders
Dystonic Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders