Clinical trial NCT03853876: A Natural History Study of Aspartylglucosaminuria
Official title: A Natural History Study of Aspartylglucosaminuria
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Aspartylglucosaminuria
Aspartylglucosamidase (AGA) Deficiency
Lysosomal Storage Diseases
Lead sponsor: Neurogene Inc.
Sponsor class: INDUSTRY
First posted: 2019-02-26
Enrollment: 8
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: Patients with a confirmed genetic diagnosis of aspartylglucosaminuria.

Brief summary: Aspartylglucosaminuria (AGU) is a rare neurodegenerative lysosomal storage disease (LSD) characterized by developmental delay, psychomotor regression, worsening intellectual disability, gait disturbance and, ultimately, premature death, and has no available treatments.

The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with AGU. This natural history study is important to better understand disease course to be able to determine clinically meaningful outcome measures for use in future clinical trials.

Detailed description: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases caused by a genetic mutation resulting in deficiency or absence of a critical enzyme, leading to the accumulation of toxic deposits in cells across multiple organ systems.

Aspartylglucosaminuria (AGU) is a rare, neurodegenerative, LSD, caused by a deficiency of the aspartylglucosaminidase (AGA) enzyme, which leads to toxic accumulation of aspartylglucosamine and subsequent cellular dysfunction. AGU has been most commonly reported in people of Finnish and Nordic descent, but is present across ethnicities and is typically misdiagnosed or undiagnosed.

Aspartylglucosaminuria (AGU) is characterized by developmental delay and intellectual disability that worsens with age. Early disease is characterized by increased frequency of bacterial ear infections, recurrent ear tube placement, intestinal dysfunction, disruptive sleep patterns, skeletal abnormalities, and gait disturbances, among others. Individuals progressively lose motor and cognitive skills, develop behavioral/emotional lability and their risk of seizures increases with age. People with AGU have a shortened life span.

No prospective natural history study for AGU has been reported. This study aims to prospectively investigate the natural history of AGU, and concurrently to identify potential outcome measures that could be used in future clinical trials. No investigational product will be provided in the study.

Eligibility criteria: Inclusion Criteria:

* Participants must have a diagnosis of AGU based on clinical presentation and genetic testing (known or suspected pathogenic mutation in AGA gene).

Exclusion Criteria:

* Patients unable to travel to UT Southwestern Medical Center and Children's Health Dallas will not be enrolled in the prospective natural history study collecting standardized clinical data; however, with participant consent, medical records will be obtained, reviewed, and recorded in the natural history database over time.

Primary outcomes:
measure: Neuropsychological Testing
timeFrame: 5 years
measure: Ophthalmological Evaluation
timeFrame: 5 years
measure: Visual Evoked Potential (VEP)
timeFrame: 5 years
measure: Brainstem Auditory Evoked Response (BAER)
timeFrame: 5 years
measure: Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS)
timeFrame: 5 years
Secondary outcomes:
measure: Adaptive functioning: Vineland Adaptive Behavior Scales, 3rd Ed
timeFrame: 5 years
measure: Language: Expressive One-Word Picture Vocabulary Test, 4th Ed, Receptive One-Word Picture Vocabulary Test, 4th Ed, NEPSY, 2nd Ed
timeFrame: 5 years
measure: Motor: NIH Toolbox Early Childhood Motor Battery or NIH Toolbox Motor Battery, 6 Minute Walk Test, Beery-Buktenica Development
timeFrame: 5 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: Neurogene Inc.
name: Elise Beausoleil
role: STUDY_DIRECTOR
References: