Clinical trial NCT03920774: The Natural History of Familial Dysautonomia
Official title: Natural History of Familial Dysautonomia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Familial Dysautonomia (Riley-Day Syndrome)
Hereditary Sensory and Autonomic Neuropathies
Hereditary Sensory and Autonomic Neuropathy 3
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2019-04-19
Enrollment: 400
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will involve as many as 400 human subjects. Registered patients range from 3 months to 66-years in age. This is a natural history study that will collect information obtained as standard of care from patients with FD.

The study will involve children as it is a genetic disease with onset at birth. Adult patients will also be enrolled.

Brief summary: The study will collect clinical information from patients with FD and allow them to give blood to help develop biological markers of the disease to aid diagnosis and treatment.

This is a non-invasive, non-interventional, observation study that poses only minimal risk for participants. The study will document the clinical features of patients with FD overtime by storing their routine clinical test results in a central database. The study will involve collaborators at other specialist clinics around the world who follow/evaluate patients with FD annually. Providing blood for future use is optional.

Detailed description: Define the phenotypic characteristics, severity and clinical evolution of FD on a patient-by patient basis. Investigators will enroll patients with FD in a multi-center observational natural history study to evaluate their biochemical, neurological and autonomic phenotype. Investigators will follow patients to systematically study the onset and scaled severity of all clinical problems. Investigators will define progression rates of patients outside of a clinical trial to distinguish between static and progressive features, a challenge in congenital neuropathies. Investigators will continue banking blood to look for ways to monitor the disease phenotypes. Biomarkers that quantify renal, cardiovascular, respiratory, skeletal and cognitive aspects of the disease will be evaluated. This information is relevant when monitoring toxicity to drugs in clinical trials. Detailed clinical follow-up of patients with FD will allow investigators to determine when standard of care therapies (e.g., non-invasive ventilation, gastrostomy feedings) should be initiated and how these impact survival outcomes.

Specific Aim 2: Develop ways to measure progressive neurological deficits as outcome measures for future clinical trials. Investigators will test the hypothesis that worsening gait ataxia and progressive visual loss are caused by ongoing neuronal degeneration. Investigators will develop precise outcome measures based on these deficits to test the efficacy of new treatments. Investigators will prospectively evaluate longitudinal changes in the retinal structure (with optical coherence tomography) and visual function in a cohort of patients with FD. Investigators will determine the extent and severity of retinal abnormalities in all patients and how they change overtime. Investigators will establish whether structural abnormalities in the retina are correlated with disease severity and look for functional correlates as measured by visual acuity and color discrimination. Following the recent discovery that gait ataxia in patients with FD is the result of sensory deficits, investigators will perform quantitative assessments of passive joint angle matching at the knee to measure proprioceptive acuity. Investigators will determine how these measures change overtime as well as their impact on daily function and quality of life.

An organized, multi-site natural history study of patients with FD will enable investigators to define disease-specific outcomes for testing new therapies, a major breakthrough for these patients. The study also offers a unique opportunity to understand better how the brain develops when devoid of crucial sensory inputs.

Eligibility criteria: Inclusion Criteria:

* Patients of any age with a diagnosis of familial dysautonomia (FD) with molecular confirmation of the IKBKAP mutation.
* Ability to provide informed consent (or assent) and comply with the study protocol

Exclusion Criteria:

* Subjects that do not wish to be a part of the study.

Primary outcomes:
measure: 1. To create a database of familial dysautonomia disorder that will serve as a phenotypic core
timeFrame: 5 years
Secondary outcomes:
measure: To define the natural history of visual function and identify predictive biomarkers of disease progression and severity.
timeFrame: 5 years
measure: To define the natural history of gait ataxia and identify predictive biomarkers of disease progression and severity
timeFrame: 5 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Dysautonomia Center - School of Medicine -NYU Langone Medical Center
state: New York
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center - Safra Children's Hospital
state: Ramat Gan
Study officials:
affiliation: NYU Langone Health
name: Horacio Kaufmann, MD
role: PRINCIPAL_INVESTIGATOR
References: