NGLY1 Deficiency: A Prospective Natural History Study

Genetic Syndrome Clinical Trial

Official title:

NGLY1 Deficiency: A Prospective Natural History Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03834987
• Other study ID #: IRB-47335
• Status: Terminated
• Start date: February 1, 2019
• Est. completion date: November 19, 2021

Study information

• Verified date: June 2022
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: November 19, 2021
• Est. primary completion date: November 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• 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

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Grace Science Foundation

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detailed phenotyping of the clinical course of NGLY1 deficiency over time	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.	5 years
Primary	Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning	Developmental assessment at baseline and longitudinally, if age and ability-appropriate.	5 years
Primary	Neurodevelopmental profile of NGLY1 deficiency as measured using Bruininks-Oseretsky Test of Motor Proficiency, Second Edition	Developmental assessment at baseline and longitudinally, if age and ability-appropriate.	5 years
Primary	Neurodevelopmental profile of NGLY1 deficiency as measured using the Peabody Scales of Motor Development	Developmental assessment at baseline and longitudinally, if age and ability-appropriate.	5 years
Primary	Neurodevelopmental profile of NGLY1 deficiency as measured using the Differential Ability Scales II	Developmental assessment at baseline and longitudinally, if age and ability-appropriate.	5 years
Primary	Neurodevelopmental profile of NGLY1 deficiency as measured using the Beery Visual Motor Integration developmental test	Developmental assessment at baseline and longitudinally, if age and ability-appropriate.	5 years
Secondary	Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL)	Quality of life will be evaluated at baseline and longitudinally.	5 years
Secondary	Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36)	Quality of life will be evaluated at baseline and longitudinally. Caregivers will complete the survey but will not be enrolled in the study.	5 years
Secondary	Biomarkers for NGLY1 deficiency identified during the course of the study	Longitudinal collection and monitoring of laboratory studies and clinical presentation as measured through standardized and quantitative assessments may identify biomarkers for NGLY1 deficiency.	5 years

External Links

•   Grace Science Foundation
•   Neurogenomics at Stanford