Clinical trial NCT03834987: NGLY1 Deficiency: A Prospective Natural History Study
Official title: NGLY1 Deficiency: A Prospective Natural History Study
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Genetic Syndrome
Keywords: NGLY1 Deficiency
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Grace Science Foundation
First posted: 2019-02-08
Enrollment: 29
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals of any age with NGLY1 deficiency.

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.


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

Primary outcomes:
measure: Detailed phenotyping of the clinical course of NGLY1 deficiency over time
timeFrame: 5 years
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning
timeFrame: 5 years
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using Bruininks-Oseretsky Test of Motor Proficiency, Second Edition
timeFrame: 5 years
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using the Peabody Scales of Motor Development
timeFrame: 5 years
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using the Differential Ability Scales II
timeFrame: 5 years
measure: Neurodevelopmental profile of NGLY1 deficiency as measured using the Beery Visual Motor Integration developmental test
timeFrame: 5 years
Secondary outcomes:
measure: Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL)
timeFrame: 5 years
measure: Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36)
timeFrame: 5 years
measure: Biomarkers for NGLY1 deficiency identified during the course of the study
timeFrame: 5 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Maura Ruzhnikov, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.