NGLY1 Deficiency: A Prospective Natural History Study

• ClinicalTrials.gov Identifier: NCT03834987
• Recruitment Status: Terminated
• First Posted: February 8, 2019
• Last Update Posted: June 8, 2022
• Sponsor: Stanford University
• Collaborator: Grace Science Foundation
• Information provided by (Responsible Party): Maura Ruzhnikov, Stanford University

Tracking Information

• First Submitted Date: January 23, 2019
• First Posted Date: February 8, 2019
• Last Update Posted Date: June 8, 2022
• Actual Study Start Date: February 1, 2019
• Actual Primary Completion Date: November 19, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 6, 2019)

• Detailed phenotyping of the clinical course of NGLY1 deficiency over time [ Time Frame: 5 years ]
  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.
• Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning [ Time Frame: 5 years ]
  Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
• Neurodevelopmental profile of NGLY1 deficiency as measured using Bruininks-Oseretsky Test of Motor Proficiency, Second Edition [ Time Frame: 5 years ]
  Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
• Neurodevelopmental profile of NGLY1 deficiency as measured using the Peabody Scales of Motor Development [ Time Frame: 5 years ]
  Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
• Neurodevelopmental profile of NGLY1 deficiency as measured using the Differential Ability Scales II [ Time Frame: 5 years ]
  Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
• Neurodevelopmental profile of NGLY1 deficiency as measured using the Beery Visual Motor Integration developmental test [ Time Frame: 5 years ]
  Developmental assessment at baseline and longitudinally, if age and ability-appropriate.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 6, 2019)

• Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) [ Time Frame: 5 years ]
  Quality of life will be evaluated at baseline and longitudinally.
• Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36) [ Time Frame: 5 years ]
  Quality of life will be evaluated at baseline and longitudinally. Caregivers will complete the survey but will not be enrolled in the study.
• Biomarkers for NGLY1 deficiency identified during the course of the study [ Time Frame: 5 years ]
  Longitudinal collection and monitoring of laboratory studies and clinical presentation as measured through standardized and quantitative assessments may identify biomarkers for NGLY1 deficiency.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: NGLY1 Deficiency: A Prospective Natural History Study
• Official Title: NGLY1 Deficiency: A Prospective Natural History Study

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Urine and blood samples.

• Sampling Method: Non-Probability Sample
• Study Population: Individuals of any age with NGLY1 deficiency.
• Condition: Genetic Syndrome

Intervention

Other: Neurodevelopmental Assessment

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

• Study Groups/Cohorts: Not Provided
• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 3, 2022): 29
• Original Estimated Enrollment (submitted: February 6, 2019): 50
• Actual Study Completion Date: November 19, 2021
• Actual Primary Completion Date: November 19, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Parent(s)/legal representative and/or participant must be willing and able to give informed consent/assent for participation in the study
• Males or females of any age
• Suspected or confirmed diagnosis of NGLY1 deficiency with genetic variants in both NGLY1 alleles and consistent clinical characteristics
• Participant and caregiver must be willing to provide clinical data, participate in standardized assessments, and provide biological samples (if living in the United States)
• Willingness to travel to Palo Alto, CA is favored, but not required

Exclusion Criteria:

• The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of NGLY1 deficiency

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03834987
• Other Study ID Numbers: IRB-47335
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan 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.

• Current Responsible Party: Maura Ruzhnikov, Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Grace Science Foundation

Investigators

• Principal Investigator: Maura Ruzhnikov, MD; Stanford University

• PRS Account: Stanford University
• Verification Date: June 2022