<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03834987</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-47335</org_study_id>
    <nct_id>NCT03834987</nct_id>
  </id_info>
  <brief_title>NGLY1 Deficiency: A Prospective Natural History Study</brief_title>
  <official_title>NGLY1 Deficiency: A Prospective Natural History Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Grace Science Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      NGLY1 deficiency is a rare genetic disorder that is characterized by: global developmental&#xD;
      delay and/or intellectual disability, hypo- or alacrima, transient elevation of&#xD;
      transaminases, and a hyperkinetic movement disorder. Significant phenotypic variability has&#xD;
      been observed in the small number of affected individuals described in the medical&#xD;
      literature.&#xD;
&#xD;
      The purpose of this study is to describe the natural history of NGLY1 deficiency in a&#xD;
      prospective, detailed, and highly uniform manner. Study participants will be closely&#xD;
      monitored over the course of five years in order to:&#xD;
&#xD;
        -  understand the clinical spectrum and progression of NGLY1 deficiency using standardized&#xD;
           clinical and neurodevelopmental assessments&#xD;
&#xD;
        -  identify clinical and biomarker endpoints for use in therapeutic trials, and&#xD;
&#xD;
        -  identify genotype-phenotype correlations&#xD;
&#xD;
      Close clinical follow-up will allow for generation of a rich dataset and detailed&#xD;
      understanding of the natural history of NGLY1 deficiency.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study concluded by Stanford University&#xD;
  </why_stopped>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">November 19, 2021</completion_date>
  <primary_completion_date type="Actual">November 19, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detailed phenotyping of the clinical course of NGLY1 deficiency over time</measure>
    <time_frame>5 years</time_frame>
    <description>Conducted in patients with NGLY1 deficiency: detailed standardized general, neurologic, dysmorphologic, and ophthalmologic evaluations; clinical laboratory studies; electroencephalogram; nerve conduction studies; quantitative studies of autonomic function; scoring of movement disorder and NGLY1 deficiency symptom scales; and a timed 10-meter walk test. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning</measure>
    <time_frame>5 years</time_frame>
    <description>Developmental assessment at baseline and longitudinally, if age and ability-appropriate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurodevelopmental profile of NGLY1 deficiency as measured using Bruininks-Oseretsky Test of Motor Proficiency, Second Edition</measure>
    <time_frame>5 years</time_frame>
    <description>Developmental assessment at baseline and longitudinally, if age and ability-appropriate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurodevelopmental profile of NGLY1 deficiency as measured using the Peabody Scales of Motor Development</measure>
    <time_frame>5 years</time_frame>
    <description>Developmental assessment at baseline and longitudinally, if age and ability-appropriate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurodevelopmental profile of NGLY1 deficiency as measured using the Differential Ability Scales II</measure>
    <time_frame>5 years</time_frame>
    <description>Developmental assessment at baseline and longitudinally, if age and ability-appropriate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurodevelopmental profile of NGLY1 deficiency as measured using the Beery Visual Motor Integration developmental test</measure>
    <time_frame>5 years</time_frame>
    <description>Developmental assessment at baseline and longitudinally, if age and ability-appropriate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL)</measure>
    <time_frame>5 years</time_frame>
    <description>Quality of life will be evaluated at baseline and longitudinally.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36)</measure>
    <time_frame>5 years</time_frame>
    <description>Quality of life will be evaluated at baseline and longitudinally. Caregivers will complete the survey but will not be enrolled in the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers for NGLY1 deficiency identified during the course of the study</measure>
    <time_frame>5 years</time_frame>
    <description>Longitudinal collection and monitoring of laboratory studies and clinical presentation as measured through standardized and quantitative assessments may identify biomarkers for NGLY1 deficiency.</description>
  </secondary_outcome>
  <enrollment type="Actual">29</enrollment>
  <condition>Genetic Syndrome</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Neurodevelopmental Assessment</intervention_name>
    <description>Developmental assessment at baseline and longitudinally as measured by age and ability-appropriate scales, including: the Mullen Scales of Early Learning, the Peabody Scales of Motor Development, the Vineland 3, and Beery Visual Motor Integration</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urine and blood samples.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals of any age with NGLY1 deficiency.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Parent(s)/legal representative and/or participant must be willing and able to give&#xD;
             informed consent/assent for participation in the study&#xD;
&#xD;
          -  Males or females of any age&#xD;
&#xD;
          -  Suspected or confirmed diagnosis of NGLY1 deficiency with genetic variants in both&#xD;
             NGLY1 alleles and consistent clinical characteristics&#xD;
&#xD;
          -  Participant and caregiver must be willing to provide clinical data, participate in&#xD;
             standardized assessments, and provide biological samples (if living in the United&#xD;
             States)&#xD;
&#xD;
          -  Willingness to travel to Palo Alto, CA is favored, but not required&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The presence of a second, confirmed disorder, genetic or otherwise, affecting&#xD;
             neurodevelopment or with other overlapping symptoms of NGLY1 deficiency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maura Ruzhnikov, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://gracescience.org/</url>
    <description>Grace Science Foundation</description>
  </link>
  <link>
    <url>https://www.stanfordchildrens.org/en/service/neurogenomics</url>
    <description>Neurogenomics at Stanford</description>
  </link>
  <results_reference>
    <citation>Levy RJ, Frater CH, Gallentine WB, Phillips JM, Ruzhnikov MR. Delineating the epilepsy phenotype of NGLY1 deficiency. J Inherit Metab Dis. 2022 May;45(3):571-583. doi: 10.1002/jimd.12494. Epub 2022 Mar 11.</citation>
    <PMID>35243670</PMID>
  </results_reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>June 3, 2022</last_update_submitted>
  <last_update_submitted_qc>June 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Maura Ruzhnikov</investigator_full_name>
    <investigator_title>Clinical Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>NGLY1 Deficiency</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Researchers and clinicians with academic interest in NGLY1 deficiency may be provided access to data obtained through this study. Any data or samples shared outside of Stanford University will be done so in a coded fashion with no protected health information included and with the execution of all applicable agreements (i.e. a material transfer agreement) or ongoing collaborations as approved in eProtocol 47335.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03834987
org study id: IRB-47335
nct id: NCT03834987
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
NGLY1 deficiency is a rare genetic disorder that is characterized by: global developmental
      delay and/or intellectual disability, hypo- or alacrima, transient elevation of
      transaminases, and a hyperkinetic movement disorder. Significant phenotypic variability has
      been observed in the small number of affected individuals described in the medical
      literature.

      The purpose of this study is to describe the natural history of NGLY1 deficiency in a
      prospective, detailed, and highly uniform manner. Study participants will be closely
      monitored over the course of five years in order to:

        -  understand the clinical spectrum and progression of NGLY1 deficiency using standardized
           clinical and neurodevelopmental assessments

        -  identify clinical and biomarker endpoints for use in therapeutic trials, and

        -  identify genotype-phenotype correlations

      Close clinical follow-up will allow for generation of a rich dataset and detailed
      understanding of the natural history of NGLY1 deficiency.
observational model: Cohort
time perspective: Prospective
measure: Detailed phenotyping of the clinical course of NGLY1 deficiency over time
time frame: 5 years
description: Conducted in patients with NGLY1 deficiency: detailed standardized general, neurologic, dysmorphologic, and ophthalmologic evaluations; clinical laboratory studies; electroencephalogram; nerve conduction studies; quantitative studies of autonomic function; scoring of movement disorder and NGLY1 deficiency symptom scales; and a timed 10-meter walk test. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning
time frame: 5 years
description: Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using Bruininks-Oseretsky Test of Motor Proficiency, Second Edition
time frame: 5 years
description: Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using the Peabody Scales of Motor Development
time frame: 5 years
description: Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using the Differential Ability Scales II
time frame: 5 years
description: Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using the Beery Visual Motor Integration developmental test
time frame: 5 years
description: Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
measure: Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL)
time frame: 5 years
description: Quality of life will be evaluated at baseline and longitudinally.
measure: Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36)
time frame: 5 years
description: Quality of life will be evaluated at baseline and longitudinally. Caregivers will complete the survey but will not be enrolled in the study.
measure: Biomarkers for NGLY1 deficiency identified during the course of the study
time frame: 5 years
description: Longitudinal collection and monitoring of laboratory studies and clinical presentation as measured through standardized and quantitative assessments may identify biomarkers for NGLY1 deficiency.
intervention type: Other
intervention name: Neurodevelopmental Assessment
description: Developmental assessment at baseline and longitudinally as measured by age and ability-appropriate scales, including: the Mullen Scales of Early Learning, the Peabody Scales of Motor Development, the Vineland 3, and Beery Visual Motor Integration
Urine and blood samples.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Maura Ruzhnikov, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
url: https://gracescience.org/
description: Grace Science Foundation
url: https://www.stanfordchildrens.org/en/service/neurogenomics
description: Neurogenomics at Stanford
citation: Levy RJ, Frater CH, Gallentine WB, Phillips JM, Ruzhnikov MR. Delineating the epilepsy phenotype of NGLY1 deficiency. J Inherit Metab Dis. 2022 May;45(3):571-583. doi: 10.1002/jimd.12494. Epub 2022 Mar 11.
PMID: 35243670
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Maura Ruzhnikov
investigator title: Clinical Assistant Professor
sharing ipd: Yes
ipd description: Researchers and clinicians with academic interest in NGLY1 deficiency may be provided access to data obtained through this study. Any data or samples shared outside of Stanford University will be done so in a coded fashion with no protected health information included and with the execution of all applicable agreements (i.e. a material transfer agreement) or ongoing collaborations as approved in eProtocol 47335.