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A Natural History Study of Aspartylglucosaminuria (AGU)

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ClinicalTrials.gov Identifier: NCT03853876
Recruitment Status : Not yet recruiting
First Posted : February 26, 2019
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Neurogene, Inc.

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.


Condition or disease
Aspartylglucosaminuria Aspartylglucosamidase (AGA) Deficiency Lysosomal Storage Diseases

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 N-acetylglucosamines 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.


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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Natural History Study of Aspartylglucosaminuria
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : August 2024





Primary Outcome Measures :
  1. Neuropsychological Testing [ Time Frame: 5 years ]

    Participants will undergo a standardized neuropsychological evaluation every 6-12 months, depending upon the assessments as follows:

    Global Cognitive: Leiter International Performance Scale, 3rd Ed, Reynolds Intellectual Assessment Scales, 2nd Ed, Mullen Scales of Early Learning

    Emotional: Aberrant Behavior Checklist, 2nd Ed, Behavior Assessment System for Children, 3rd Ed

    Behavioral functioning: Aberrant Behavior Checklist, 2nd Ed, Behavior Assessment System for Children, 3rd Ed


  2. Ophthalmological Evaluation [ Time Frame: 5 years ]
    Participants will undergo an ophthalmological assessment every 6 months to better characterize the involvement of the eye in AGU.

  3. Visual Evoked Potential (VEP) [ Time Frame: 5 years ]
    Participants will undergo a VEP test every 6 months to evaluate electrical signal transmission through the visual pathway from the retina to the visual cortex.

  4. Brainstem Auditory Evoked Response (BAER) [ Time Frame: 5 years ]
    Participants will undergo a BAER test every 6 months to evaluate electrical signal transmission from the 8th cranial nerve to the brainstem and the cortex in response to certain tones.

  5. Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS) [ Time Frame: 5 years ]
    An MRI scan of the brain will be performed annually to characterize the structural abnormalities associated with AGU. MRS will be performed on regions of interest in the brain.


Secondary Outcome Measures :
  1. Adaptive functioning: Vineland Adaptive Behavior Scales, 3rd Ed [ Time Frame: 5 years ]
    Participants will undergo a standardized neuropsychological evaluation every 6-12 months

  2. Language: Expressive One-Word Picture Vocabulary Test, 4th Ed, Receptive One-Word Picture Vocabulary Test, 4th Ed, NEPSY, 2nd Ed [ Time Frame: 5 years ]
    Participants will undergo a standardized neuropsychological evaluation every 6-12 months

  3. Motor: NIH Toolbox Early Childhood Motor Battery or NIH Toolbox Motor Battery, 6 Minute Walk Test, Beery-Buktenica Development [ Time Frame: 5 years ]
    Participants will undergo a standardized neuropsychological evaluation every 6-12 months


Biospecimen Retention:   None Retained
Patients will also be given the opportunity to have serum samples stored for up to 10 years for future exploratory analyses.


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with a confirmed genetic diagnosis of aspartylglucosaminuria.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03853876


Contacts
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Contact: Call Center 877-237-5020 medicalinfo@neurogene.com

Sponsors and Collaborators
Neurogene, Inc.
Investigators
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Principal Investigator: Kimberly Goodspeed, MD UT- Southwestern

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Responsible Party: Neurogene, Inc.
ClinicalTrials.gov Identifier: NCT03853876     History of Changes
Other Study ID Numbers: STU 2018-0017
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lysosomal Storage Diseases
Aspartylglucosaminuria
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases