NGLY1 Deficiency: A Prospective Natural History Study

Terminated

• Conditions: Genetic Syndrome

• Registration Number: NCT03834987
• Lead Sponsor: Stanford University

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 available

Study Timeline

• Study First Submitted: 2019-01-23
• Study Start: 2019-02-01
• Study First Submitted QC: 2019-02-06
• Study First Posted: 2019-02-08
• Primary Completion: 2021-11-19
• Study Completion: 2021-11-19
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-03
• Last Update Posted: 2022-06-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

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

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Detailed phenotyping of the clinical course of NGLY1 deficiency over time	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	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	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	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	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	5 years	Developmental assessment at baseline and longitudinally, if age and ability-appropriate.

Secondary Outcome Measures

Name	Time	Method
Biomarkers for NGLY1 deficiency identified during the course of the study	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.
Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL)	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)	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.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States