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The Natural History of Familial Dysautonomia

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03920774
Recruitment Status : Recruiting
First Posted : April 19, 2019
Last Update Posted : May 13, 2020
Information provided by (Responsible Party):
NYU Langone Health

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.

Condition or disease
Familial Dysautonomia (Riley-Day Syndrome) Hereditary Sensory and Autonomic Neuropathies Hereditary Sensory and Autonomic Neuropathy 3

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.

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History of Familial Dysautonomia
Actual Study Start Date : February 22, 2017
Estimated Primary Completion Date : February 21, 2022
Estimated Study Completion Date : December 31, 2022

Familial Dysautonomia
Patients diagnosed with familial dysautonomia, a genetic disorder that affects the development and survival of nerve cells in the autonomic nervous system. It primarily affects neurons that control involuntary actions like regulation of blood pressure and breathing. It also affects the sensory nervous system and the perception of pain, heat and cold.

Primary Outcome Measures :
  1. 1. To create a database of familial dysautonomia disorder that will serve as a phenotypic core [ Time Frame: 5 years ]
    Investigators will create an enrollment database of patients with familial dysautonomia. All patients will have standardized phenotypic evaluations that will combine clinical, physiological and biochemical strategies to characterize complex autonomic phenotypes, both known and still undiscovered.

Secondary Outcome Measures :
  1. To define the natural history of visual function and identify predictive biomarkers of disease progression and severity. [ Time Frame: 5 years ]
    Investigators will map the natural history of visual function including retinal structure and visual acuity and test the hypothesis that worsening visual loss is caused by ongoing neuronal degeneration.

  2. To define the natural history of gait ataxia and identify predictive biomarkers of disease progression and severity [ Time Frame: 5 years ]
    Investigators will map the natural history of gait ataxia and test the hypothesis that progressive ataxia is correlated with increasing loss of proprioceptive acuity caused by ongoing death of sensory neurons.

Biospecimen Retention:   Samples With DNA
optional blood sample

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


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.

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): NCT03920774

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Contact: Maria Cotrina, PhD 212 263 7225
Contact: Lucy Norcliffe-Kaufmann, PhD 212 263 7225

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United States, New York
Dysautonomia Center - School of Medicine -NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Maria Cotrina, Ph D    212-263-7225   
Contact: Lucy Norcliffe-Kaufmann, PhD    212 263 7225   
Sheba Medical Center - Safra Children's Hospital Recruiting
Tel HaShomer, Ramat Gan, Israel, 52621
Contact: Bat El Bar Aluma, MD    +972 52 666 8335   
Contact: Reut Ramon, MPH    +972 52 666 7031   
Sponsors and Collaborators
NYU Langone Health
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Principal Investigator: Lucy Norcliffe-Kaufmann, PHD NYU Langone Health
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Responsible Party: NYU Langone Health Identifier: NCT03920774    
Other Study ID Numbers: i16-01774
First Posted: April 19, 2019    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020

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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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Nervous System Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Dysautonomia, Familial
Hereditary Sensory and Autonomic Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Malformations
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn