GM1 and GM2 Gangliosidosis PROspective Neurological Disease TrajectOry Study (PRONTO) (PRONTO)

Prospective Longitudinal Study of Neurological Disease Trajectory in Children Living With Late-Infantile or Juvenile Onset of GM1 or GM2 Gangliosidosis

The study aims to characterize prospectively longitudinal progression of neurological domains in GM1 and GM2 Gangliosidosis patients with high-quality standards (GCP compliant).

Study Overview

• Status: Completed
• Conditions: GM1 Gangliosidosis; Tay-Sachs Disease; Sandhoff Disease

Detailed Description

The study is a prospective longitudinal, multicentric decentralized trial which will be performed in children diagnosed with late infantile or juvenile onset of neurological disease of either GM1 or GM2 Gangliosidoses (Tay-Sachs or Sandhoff disease). The study anticipates to include a total of approximately 35 patients. A large set of neurological functions will be evaluated by rating scales used by physicians and questionnaires answered by parents. Digital tools will be used to support the study procedures with virtual visits.

• Study Type: Observational
• Enrollment (Actual): 31

Contacts and Locations

Study Locations

• Brazil
  • Curitiba, Brazil
    • Hospital Pequeno Principe
  • Porto Alegre, Brazil
    • Hospital de Clinicas de Porto Alegre
• France
  • Marseille, France
    • Hopital d'Enfants CHU Timone
  • Paris, France
    • Armand-Trousseau Children's Hospital - CHU Paris Est
  • Toulouse, France
    • Hôpital des Enfants - CHU Toulouse Purpan
• Germany
  • Giessen, Germany
    • Universtitäsklinikum Giessen und Marburg
  • Munich, Germany
    • LMU - Klinikum der Universitaet Muenchen - Neurologische Klinik und Poliklinik
• Italy
  • Catania, Italy
    • Universita' di Catania
  • Milan, Italy
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
  • Udine, Italy
    • University Hospital Friuli Centrale
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital NHSFT
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with diagnosis of GM1 Gangliosidosis Tay-Sachs disease, or Sandhoff disease, or late infantile or juvenile onset of neurological disease

Description

Inclusion Criteria:

• Genetically confirmed GM1 Gangliosidosis or genetically confirmed Tay-Sachs or Sandhoff disease
• Onset of neurological symptoms on or after the patient's first birthday
• Achieved 12-month developmental milestones at normal developmental time points as per Principal Investigator's judgement
• Abnormal gait and/or speech disturbance

Exclusion Criteria:

• Patients who have received (within 6 months before screening), are currently receiving or are planned to receive (within the following 6 months) gene therapy, stem cell transplantation, experimental drugs, or any drug, which, in the Investigator´s opinion, may (have) interfere(d) with disease progression

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cohort; Late infantile or juvenile onset for GM1 or GM2 Gangliosidosis. The study anticipates to include a total of approximately 35 patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Gait 9-point item score of the Scale for Assessment and Rating of Ataxia (SARA)	Score between 0 (better) and 8 (worse) points	0-4 years
Change in the Speech 7-point item score of SARA	Score between 0 (better) and 6 (worse) points	0-4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in scores of SARA items Stance (7-point), Sitting (5-point), Finger chase (5-point), Nose-finger test (5-point), Fast alternating hand movement (5-point), Heel-shin slide (5-point) and overall score.	Stance score between 0 (better) and 6 (worse) points Sitting score between 0 (better) and 4 (worse) points Finger chase test score between 0 (better) and 4 (worse) points Nose-finger test score between 0 (better) and 4 (worse) points Fast alternating hand movements test score between 0 (better) and 4 (worse) points Heel-shin slide score between 0 (better) and 4 (worse) points	0-4 years
Change in the total score of the Motor Function Measure-32 (MFM-32), and each of the 3 domains	The scoring of each item uses a 4-point Likert scale - score between 0 (worse) and 3 (better)	0-4 years
Change of Timed Up & Go	Time a patient takes to rise from a chair, walk 3 meters, turn around 180°, walk back to the chair, and sit down while turning 180°	0-4 years
Change in swallowing score	Assessment of patient swallowing ability - score between 0 (better) and 5 (worse)	0-4 years
Change in the overall composite score of the Vineland Adaptive Behavioral Scale (VABS)	Rated on 0 (never performed),1, 2 (habitually performed) scale	0-4 years
Change in BSFC-s score for each of the 10 items and overall score	Rated on a 4-point scale with the values "strongly disagree", "disagree", "agree", and "strongly agree"	0-4 years
Collection of seizures events, choking episodes, respiratory tract infections	Gathering data about presence/absence and frequency of seizures, choking episodes, respiratory tract infections	0-4 years

Collaborators and Investigators

• Sponsor: Azafaros A.G.
• Investigators: Study Director: Ruben Giorgino, MD, PhD, Azafaros A.G.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Actual): September 16, 2025
• Study Completion (Actual): September 16, 2025

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Natural History Study; Genetic Diseases, Inborn; GM1 Gangliosidosis; GM2 Gangliosidosis; Lysosomal Storage Disorders; Tay-Sachs disease; Sandhoff disease; Hexosaminidase A and B deficiency; β-galactosidase deficiency
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Metabolism, Inborn Errors; Metabolic Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Sphingolipidoses; Lipidoses; Gangliosidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Genetic Diseases, Inborn; Nervous System Diseases; Lysosomal Storage Diseases; Gangliosidosis, GM1; Gangliosidoses, GM2; Tay-Sachs Disease; Sandhoff Disease
• Other Study ID Numbers: AZA-001-5A4-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No