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A Natural History Study of hnRNP-related Disorders

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ClinicalTrials.gov Identifier: NCT03492060
Recruitment Status : Recruiting
First Posted : April 10, 2018
Last Update Posted : September 27, 2018
Sponsor:
Collaborator:
Simons Foundation
Information provided by (Responsible Party):
Jennifer Bain, Columbia University

Brief Summary:
The purpose of this study is to analyze patterns in individuals with hnRNP genetic variants, including their neurological comorbidities, other medical problems and any treatment. The investigators will maintain an ongoing database of medical data that is otherwise being collected for routine medical care. The investigators will also collect data prospectively in the form of questionnaires, neuropsychological assessments, motor assessments, and electroencephalography to examine the landscape of deleterious variants in these genes.

Condition or disease
Neurodevelopmental Disorders Intellectual Disability Developmental Delay Autism Spectrum Disorder Seizures Hypertonia, Muscle Hypotonia

Detailed Description:

Neurodevelopmental disorders are a group of disorders in which the development of the central nervous system is disturbed. The genetic basis for many neurodevelopmental disorders has continued to expand and a recent gene called HNRNPH2 (Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2) is one such gene that is associated with a common neurodevelopmental disorder characterized by developmental delay, intellectual disability, autism and autistic features, and tone abnormalities, among other multisystem problems.

The investigators will expand the genetic cohort to include any individual with a variant in an hnRNP gene presenting with neurodevelopmental abnormalities. This is non-interventional study that examines both data previously used in clinical practice and prospective data collection in the form of questionnaires and assessments. The investigators will examine patterns of initial presentation, patterns in neurological evaluations; neurological testing including brain MRI and electroencephalography, and outcomes in individuals with a variant in any hnRNP gene.

Genes of Focus:

hnRNPA1 hnRNPA2 hnRNPB1 hnRNPB2 hnRNPC2 hnRNPD hnRNPE1 hnRNPE2 hnRNPE3 hnRNPE4 hnRNPG hnRNPH1 hnRNP H2 hnRNPI hnRNPK hnRNPL hnRNPM hnRNPP hnRNPQ1 hnRNPQ2 hnRNPQ3 hnRNPR hnRNPU


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: A Natural History Study of hnRNP-related Disorders
Actual Study Start Date : June 13, 2018
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine


Group/Cohort
Variant in any hnRNP gene
Individuals with a variant in any hnRNP gene who present with neurodevelopmental abnormalities are eligible for the study.



Primary Outcome Measures :
  1. Medical abnormalities associated with a mutation in any hnRNP gene [ Time Frame: 5 years ]
    Variants in hnRNP genes are known to result in a variety of clinical phenotypes. The study is intended to accrue data from medical records that document the range of neurological phenotypes and statistically explore their frequency in the genetic cohort.

  2. Education-based impairments associated with a mutation in any hnRNP gene [ Time Frame: 5 years ]
    The study seeks to collect records from the schools attended by participants; including: Individualized Education Programs (IEPs) and school records. We intend to use these records, in tandem with medical records, to explore meaningful statistical and clinical relationships in the phenotypes expressed by the population of the study.

  3. Repetitive Behavior [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and repetitive behavior (measured by the Repetitive Behavior Scale - Revised; RBS-R)

  4. Sleep Habits [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and sleep habits (measured by The Children's Sleep Habits Questionnaire; CSHQ)

  5. Sensory Issues [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and sensory issues (measured by The Short Sensory Profile; SSP)

  6. Social Interaction and Communication SRS-II Score [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Responsiveness Scale - Second Edition; SRS-II)

  7. Anxiety [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and anxiety (measured by The Spence Children's Anxiety Scale - Preschool and Parent Reports; SCAS - Preschool and SCAS - P)

  8. Receptive Language Skills [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and receptive language skills (measured by a 20-item music exposure questionnaire evaluating exposure on a 3-point scale: rarely, sometimes, often; and an EEG with music paradigm)

  9. Executive Functioning [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and executive functioning (measured by The Behavior Rating Inventory of Executive Function - Parent Report; BRIEF-P)

  10. Autism [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and autism (measured by The Childhood Autism Rating Scale; CARS)

  11. Adaptive Behavior [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and adaptive behavior (measured by The Vineland Adaptive Behavior Scales, Second Edition; Vineland - 2)

  12. Social Interaction and Communication SCQ Score [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Communication Questionnaire; SCQ)

  13. Emotional Regulation [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and emotional regulation (measured by The Behavioral Assessment System for Children - Third Edition; BASC - 3)

  14. Motor Performance [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and motor performance (measured by The Movement Assessment Battery for Children - Second Edition; MASC-II)

  15. Function in Daily Activities, Mobility, Social and Cognitive, and Responsibility [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and functional capability in daily activities and mobility (measured by The Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PEDI-CAT)

  16. Functional Balance [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and functional balance and gross motor function (measured by a 14-item Pediatric Balance Scale)

  17. Functional Capability and Mobility [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and functional mobility (measured by an 11-point Movement Questionnaire)

  18. Coordination and Gait [ Time Frame: 5 years ]
    Correlations (r) between mutant allele (obtained from retrospective data) and gait (measured by a Kinematic Evaluation utilizing Solesound Pedishoe Sandals and GaitRite Walkway)


Biospecimen Retention:   Samples With DNA
The investigators will be collecting urine [30oz or 90 milliliters], blood [5 milliliters or 1 teaspoon], and skin tissue [4mm using punch biopsy] samples from subjects seen by the PI for routine clinical care.


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:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals who have already undergone genetic testing and carry a variant in any hnRNP gene.
Criteria

Inclusion Criteria:

  • Individuals must have had whole genome/exome sequencing and have a confirmed variant in any hnRNP gene.

Exclusion Criteria:

  • Subjects who cannot provide genetic confirmation of a predicted deleterious variant in any hnRNP 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 ClinicalTrials.gov identifier (NCT number): NCT03492060


Contacts
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Contact: Jennifer M. Bain, MD, PhD 646-426-3876 jb3634@cumc.columbia.edu
Contact: Olivia S. Thornburg, BA 347-802-5314 ost2103@cumc.columbia.edu

Locations
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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Sub-Investigator: Wendy K. Chung, MD, PhD         
Sponsors and Collaborators
Columbia University
Simons Foundation
Investigators
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Principal Investigator: Jennifer M. Bain, MD, PhD Columbia University

Additional Information:
Publications:
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Responsible Party: Jennifer Bain, Assistant Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier: NCT03492060     History of Changes
Other Study ID Numbers: AAAR7203
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: September 27, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data will be shared with Simons VIP. This is applicable only to participants enrolled in Simons Variation in Individuals Project (VIP) prior to enrollment in our study (as stipulated in the consent process). Individual data for all primary and secondary outcome measures will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be available per request as it is accrued throughout the course of the study.
Access Criteria: Data access requests will be reviewed by the PI and study team. Requestors will be required to sign a data access agreement.
URL: https://simonsfoundation.org

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

Keywords provided by Jennifer Bain, Columbia University:
Gene Variant
HNRNPA1
HNRNPA2
HNRNPB1
HNRNPC1
HNRNPC2
HNRNPD
HNRNPE1
HNRNPE2
HNRNPE3
HNRNPE4
HNRNPG
HNRNPH1
HNRNPH2
HNRNPI
HNRNPK
HNRNPL
HNRNPM
HNRNPP
HNRNPQ1
HNRNPQ2
HNRNPQ3
HNRNPR
HNRNPU

Additional relevant MeSH terms:
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Disease
Seizures
Autism Spectrum Disorder
Intellectual Disability
Neurodevelopmental Disorders
Muscle Hypotonia
Muscle Hypertonia
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Child Development Disorders, Pervasive
Mental Disorders
Neurobehavioral Manifestations
Neuromuscular Manifestations