NGLY1 DeficiencyNCT06122766
NGLY1 Natural History
An observational study of NGLY1 Deficiency, run by Baylor College of Medicine at 1 site in United States.
Trial summary
N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement… Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- NGLY1 Deficiency
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2023to 24 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy.
Who may be able to join
- Individuals aged 2 to 25 years with a confirmed molecular diagnosis of NGLY1 Deficiency.
Who cannot join
- Prior or current participation in a therapeutic trial for NGLY1 Deficiency (note that neither the plan for future participation in an interventional trial nor participation in previous pilot study preclude entering this trial).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of NGLY1 Deficiency Movement Disorder & Clinical Features
N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy. The condition was first reported in 2012 and thus comprehensive characterization of the disease, especially its unique movement disorder, continues to be described.
The hyperkinetic movement disorder in NGLY1 Deficiency is highly complex and has been qualitatively described to include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. These descriptors apply to both lower and upper limb movement in individuals with NGLY1 Deficiency.
Read more
Preliminary results indicate that NGLY1 Deficiency is associated with a myriad of movement control problems and range from being unable to perform certain arm movements or walk to behaviors that appear quite similar to age-matched neurotypical individuals. Preliminary results suggest that when reaching for objects, arm motion patterns tend to display unusual joint and hand trajectories, relative to neurotypical individuals, thereby decreasing their effectiveness/efficiency. During gait, range of joint motion, particularly at the knee, was often significantly reduced combined with evidence of leg movement asymmetry. Additionally, preliminary results indicate that there is low frequency tremor, particularly in the upper limbs, that tends to decline during arm acceleration. These preliminary findings, if confirmed in a larger sample, provide entryways to the understanding of how NGLY1 Deficiency impacts movement control and thereby may serve both as diagnostic and therapeutic endpoints for physicians and therapists.
The purpose of this natural history study in NGLY1 Deficiency is to collect longitudinal measurements of movement concurrently with clinical and biomarker measures to aid in the development in end points for future therapeutic trials.
Read the detailed description
This is a single center, longitudinal descriptive study of the concurrent movement disorders and neurodevelopmental and clinical status in children with NGLY1 Deficiency.
Subjects will be recruited through the Grace Science Foundation (GSF), a patient advocacy organization focused on NGLY1 Deficiency. GSF will post on social media institutional review board (IRB)-approved information regarding the study. We will gather (1) detailed standardized motor function measures, (2) blood samples for laboratory analysis, and (3) clinical measures including growth and neurodevelopmental assessments.
Assessments will occur at four time points: Visit 1 (baseline), Visit 2 (6 months ± 4 weeks), Visit 3 (12 months ± 4 weeks) and Visit 4 (24 months ± 4 weeks).
Clinical and laboratory measures will be collected to aid in analysis and to document factors which may impact the movement disorder as well as overall disease progression.
Standard descriptive statistics will be used to evaluate all demographic and other clinical subject information.
The clinical data will be analyzed by a child neurologist, developmental pediatrician, or neuropsychologist by standard descriptive statistics (e.g. mean and standard deviation, T-tests). Movement data from the sub-domains of Bayley and Vineland, GMFM-88 and GMFCS, E \& R will be compared against normative data and against longitudinal data obtained. Analyses will be performed at baseline evaluation, as well as the second and third timepoints.
STUDY ASSESSMENTS:
- Physical Examination: A physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal, skin, and musculoskeletal systems.
- Height, weight, and head circumference will also be measured and recorded.
- Medical History
- Neurological Examination
- Ophthalmologic Examination
- Gross Motor Function Measure (GMFM-88):The GMFM-88 is an assessment tool designed to measure changes in gross motor function over time (Harvey 2017) or with intervention in children with cerebral palsy.
- Gross Motor Function Classification System, Expanded \& Revised (GMFCS, E \& R):The GMFCS - E\&R is a 5-level classification system that describes the gross motor function of children and youth on the basis of their self-initiated movement with particular emphasis on sitting, walking, and wheeled mobility; it was developed for children with cerebral palsy and has been used with other neuromuscular pediatric diseases.
- Communication Function Classification System (CFCS): The purpose of the CFCS is to classify the everyday communication performance of an individual with cerebral palsy into one of five levels
- Bayley Scales of Infant and Toddler Development - Fourth Edition (BSID-4): The BSID-4 (Bayley 2019) is designed for infants and toddlers from 16 days to 42 months of age, but due to the level of impairment in individuals with NGLY1 Deficiency, the scale will be utilized independent of the age of the subject so age-independent normative scores will be analyzed.
- Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV): The WPPSI-IV will be performed at each visit if subjects are too highly functioning for the Bayley and have aged out. The WPPSI-IV uses subtests and composite scores to assess a student's general intellectual ability and cognitive functioning based on their test performance and chronologic age.
- Vineland Adaptative Behavior Scale - Version 3 (Vineland 3):The Vineland-3 measures adaptive functioning, specifically communication, daily living skills, socialization, and motor skills
- Clinician Global Impression of Severity (CGI-S) and Clinician Global Impression of Change (CGI-C):The CGI-S, adapted for NGLY1 Deficiency, assesses severity of the subject's symptoms of NGLY1 Deficiency.
- Caregiver Global Impression of Severity (CaGI-S) and Caregiver Global Impression of Change (CaGI-C):The CaGI-S, adapted for NGLY1 Deficiency, assesses severity of the subject's symptoms of NGLY1 Deficiency based on the caregiver's impression.
- Blood Draw: Plasma GNA Biomarkers and Liver Function Test
- Conditions
- NGLY1 Deficiency
- Medical subject headings
- NGLY1 deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| N-glycanase 1 (NGLY1) Deficiency | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize movement and gait disorder
in a larger cohort of NGLY1 Deficiency subjects
Measured: 24 months
Secondary outcomes (2)
To determine the progression of movement disorder parameters
via collection of longitudinal data
Measured: 24 months
To describe associations between movement disorder parameters with relevant clinical measures
such as neurodevelopmental assessments and laboratory values
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2023
- Study start27 Feb 2023
- Primary completion24 Oct 2024
- Study completion24 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NGLY1 DeficiencyStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Grace Science Foundation
- Responsible party
- Principal investigator, Bernhard Suter, Baylor College of Medicine
- Investigators
- Bernhard Suter, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06122766
- Sponsor's protocol ID
- H-49928
- Status last verified
- Dec 2024
- First submitted
- 2 Nov 2023
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of NGLY1 Deficiency Movement Disorder & Clinical Features
- ClinicalTrials.gov ID
- NCT06122766
- Acronym / sponsor ID
- H-49928
- Conditions
- NGLY1 Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Grace Science Foundation
- Study start
- 27 Feb 2023 (actual)
- Primary completion
- 24 Oct 2024 (actual)
- Study completion
- 24 Oct 2024 (actual)
- First posted
- 8 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy. The condition was first reported in 2012 and thus comprehensive characterization of the disease, especially its unique movement disorder, continues to be described.
The hyperkinetic movement disorder in NGLY1 Deficiency is highly complex and has been qualitatively described to include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. These descriptors apply to both lower and upper limb movement in individuals with NGLY1 Deficiency.
Preliminary results indicate that NGLY1 Deficiency is associated with a myriad of movement control problems and range from being unable to perform certain arm movements or walk to behaviors that appear quite similar to age-matched neurotypical individuals. Preliminary results suggest that when reaching for objects, arm motion patterns tend to display unusual joint and hand trajectories, relative to neurotypical individuals, thereby decreasing their effectiveness/efficiency. During gait, range of joint motion, particularly at the knee, was often significantly reduced combined with evidence of leg movement asymmetry. Additionally, preliminary results indicate that there is low frequency tremor, particularly in the upper limbs, that tends to decline during arm acceleration. These preliminary findings, if confirmed in a larger sample, provide entryways to the understanding of how NGLY1 Deficiency impacts movement control and thereby may serve both as diagnostic and therapeutic endpoints for physicians and therapists.
The purpose of this natural history study in NGLY1 Deficiency is to collect longitudinal measurements of movement concurrently with clinical and biomarker measures to aid in the development in end points for future therapeutic trials.
Detailed description
This is a single center, longitudinal descriptive study of the concurrent movement disorders and neurodevelopmental and clinical status in children with NGLY1 Deficiency.
Subjects will be recruited through the Grace Science Foundation (GSF), a patient advocacy organization focused on NGLY1 Deficiency. GSF will post on social media institutional review board (IRB)-approved information regarding the study. We will gather (1) detailed standardized motor function measures, (2) blood samples for laboratory analysis, and (3) clinical measures including growth and neurodevelopmental assessments.
Assessments will occur at four time points: Visit 1 (baseline), Visit 2 (6 months ± 4 weeks), Visit 3 (12 months ± 4 weeks) and Visit 4 (24 months ± 4 weeks).
Clinical and laboratory measures will be collected to aid in analysis and to document factors which may impact the movement disorder as well as overall disease progression.
Standard descriptive statistics will be used to evaluate all demographic and other clinical subject information.
The clinical data will be analyzed by a child neurologist, developmental pediatrician, or neuropsychologist by standard descriptive statistics (e.g. mean and standard deviation, T-tests). Movement data from the sub-domains of Bayley and Vineland, GMFM-88 and GMFCS, E \& R will be compared against normative data and against longitudinal data obtained. Analyses will be performed at baseline evaluation, as well as the second and third timepoints.
STUDY ASSESSMENTS:
- Physical Examination: A physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal, skin, and musculoskeletal systems.
- Height, weight, and head circumference will also be measured and recorded.
- Medical History
- Neurological Examination
- Ophthalmologic Examination
- Gross Motor Function Measure (GMFM-88):The GMFM-88 is an assessment tool designed to measure changes in gross motor function over time (Harvey 2017) or with intervention in children with cerebral palsy.
- Gross Motor Function Classification System, Expanded \& Revised (GMFCS, E \& R):The GMFCS - E\&R is a 5-level classification system that describes the gross motor function of children and youth on the basis of their self-initiated movement with particular emphasis on sitting, walking, and wheeled mobility; it was developed for children with cerebral palsy and has been used with other neuromuscular pediatric diseases.
- Communication Function Classification System (CFCS): The purpose of the CFCS is to classify the everyday communication performance of an individual with cerebral palsy into one of five levels
- Bayley Scales of Infant and Toddler Development - Fourth Edition (BSID-4): The BSID-4 (Bayley 2019) is designed for infants and toddlers from 16 days to 42 months of age, but due to the level of impairment in individuals with NGLY1 Deficiency, the scale will be utilized independent of the age of the subject so age-independent normative scores will be analyzed.
- Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV): The WPPSI-IV will be performed at each visit if subjects are too highly functioning for the Bayley and have aged out. The WPPSI-IV uses subtests and composite scores to assess a student's general intellectual ability and cognitive functioning based on their test performance and chronologic age.
- Vineland Adaptative Behavior Scale - Version 3 (Vineland 3):The Vineland-3 measures adaptive functioning, specifically communication, daily living skills, socialization, and motor skills
- Clinician Global Impression of Severity (CGI-S) and Clinician Global Impression of Change (CGI-C):The CGI-S, adapted for NGLY1 Deficiency, assesses severity of the subject's symptoms of NGLY1 Deficiency.
- Caregiver Global Impression of Severity (CaGI-S) and Caregiver Global Impression of Change (CaGI-C):The CaGI-S, adapted for NGLY1 Deficiency, assesses severity of the subject's symptoms of NGLY1 Deficiency based on the caregiver's impression.
- Blood Draw: Plasma GNA Biomarkers and Liver Function Test
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N-glycanase 1 (NGLY1) Deficiency | – | – |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy.
Key inclusion criteria (1 listed)
- Individuals aged 2 to 25 years with a confirmed molecular diagnosis of NGLY1 Deficiency.
Key exclusion criteria (1 listed)
- Prior or current participation in a therapeutic trial for NGLY1 Deficiency (note that neither the plan for future participation in an interventional trial nor participation in previous pilot study preclude entering this trial).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To characterize movement and gait disorder
Time frame: 24 months
in a larger cohort of NGLY1 Deficiency subjects
2 secondary outcomes
To determine the progression of movement disorder parameters
Time frame: 24 months
To describe associations between movement disorder parameters with relevant clinical measures
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
Related trials for NGLY1 Deficiency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernhard Suter, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NGLY1 Deficiency, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize movement and gait disorder (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.