GM1 GangliosidosisNCT04041102
Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients
An observational study of GM1 Gangliosidosis, run by University of Pennsylvania at 6 sites in 5 countries.
Trial summary
Owing to the rarity, severity, speed of progression and fatal prognosis of infantile and juvenile GM1, there is a limited understanding of overall disease progression and meaningful outcome measures. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- GM1 Gangliosidosis
- How many people
- 31 participants
- Where
- 6 sitesin 5 countries
- Study dates
- 12 Jun 2020to 1 May 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals with a diagnosis of infantile (Type 1) or juvenile (Type 2) GM1 gangliosidosis.
Who may be able to join
- Documentation/ Confirmation of reduced beta-galactosidase enzyme activity in leukocytes
- Confirmed diagnosis of infantile or juvenile GM1 gangliosidosis with documentation of GLB1 mutations
- Parent/Caregiver capable of providing informed consent (if cognitively able, child to provide assent as well)
- Infantile (Type 1) GM1 subjects: Documented symptom onset by 6 months of age with significant hypotonia on exam or history elicited from parent(s)/ caregiver(s)
- Juvenile (Type 2) GM1 subjects: Documented symptom onset after 6 months of age OR documented symptom onset prior to 6 months of age without significant hypotonia on exam or elicited from parent(s)/ caregiver(s)
Who cannot join
- Enrollment in any other clinical study with an investigational product/ therapy (patients receiving miglustat off-label will be eligible)
- Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or a secondary cause that may, in the opinion of the investigator, confound interpretation of study results
- Any condition that, in the opinion of the investigator, would put the subject at undue risk or make it unsafe for the subject to participate
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
United States2 sites
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94610
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Canada1 site
Montreal Children's Hospital Research Institute - McGill University
Montreal, Quebec
United Kingdom1 site
UCL Great Ormond Street Institute of Child Health
London
About this study
Owing to the rarity, severity, speed of progression and fatal prognosis of infantile and juvenile GM1, there is a limited understanding of overall disease progression and meaningful outcome measures. This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of GM1 disease progression and clinical outcome. Having a GM1 natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials.
This natural history study will follow up to 40 subjects diagnosed with GM1 gangliosidosis (up to 20 infantile (Type 1) and 20 late infantile/juvenile (Type 2)) for up to 3 years. Visits will be conducted every 6 months, during which several procedures will be performed and the data recorded in order to learn about the natural course of the disease, including changes in clinical and neurological assessments and electrophysiologic, imaging and biofluid biomarkers. Study procedures include: physical \& neurological exam, blood \& urine sample collection, questionnaires \& assessments of development, seizure diary, ECHO, ECG, x-ray and ultrasound (if MRI not performed), EEG and genetic testing (if not already done).
The following procedures are subject to local/institutional policies and the medical discretion of the Study Physician: MRI, lumbar puncture (spinal tap) and General anesthesia/sedation (for MRI and LP).
- Conditions
- GM1 Gangliosidosis
- Keywords
- GM1, GM1 gangliosidosis, GM1 Type 1, GM1 Type 2, GM1 gangliosidosis Type 1, GM1 gangliosidosis Type 2, GM1 natural history study, GM1 gangliosidosis natural history study, Lysosomal Storage Disorders, Lysosomal Disorders
- Medical subject headings
- Gangliosidosis, GM1, Lysosomal Storage Diseases
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 |
|---|---|---|
| Infantile (Type 1) or Juvenile (Type 2) GM1 Gangliosidosis | This study observes one cohort: up to 40 Infantile GM1 (Type 1) or Juvenile GM1 (Type 2) subjects. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival (Infantile GM1 population)
Survival will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Measured: Baseline through 36 months (3 years)
Presence of and dependence on feeding tube (Infantile GM1 population)
The presence of a feeding tube and dependence on the feeding tube, if applicable, will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Measured: Baseline through 36 months (3 years)
Change from baseline in standard scores for each domain on the Vineland-II (Juvenile GM1 population)
The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is a standard assessment for measuring personal and social skills for children and adults (birth through 90 years of age). This assessment aids in diagnosis of intellectual and developmental disabilities or delays associated with a variety of diseases/disorders. The assessment includes 5 domains. Scores for each domain and a composite adaptive behavior score are then converted to standard scores with a range of 20 to 140, with a score of 140 correlating to a high adaptive level.
Measured: Baseline through 36 months (3 years)
Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Juvenile GM1 population)
Based on the outcome of the Vineland-II, each subject will be given a developmental age score that will determine whether the Bayley Scale of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II) is administered. Children with a developmental age of 42 months or less will be administered the BSID-III and those with a developmental age of greater than 42 months will be administered the KABC-II.
The BSID-III assesses 5 major areas of development. Each domain results in a raw score that is converted to a composite score. A higher composite score generally corresponds with higher function.
The KABC-II assesses 4 major areas of intelligence and achievement in young children. Each domain results in a raw score that is converted to a standard score. Scores from 90-109 are generally considered average, with scores higher than 109 considered to be above average.
Measured: Baseline through 36 months (3 years)
Secondary outcomes (13)
Survival (Juvenile GM1 population)
Survival will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Measured: Baseline through 36 months (3 years)
Presence of and dependence on feeding tube (Juvenile GM1 population)
The presence of a feeding tube and dependence on the feeding tube, if applicable, will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Measured: Baseline through 36 months (3 years)
Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Infantile GM1 population)
See these outcome measures described above for full details.
The BSID-III or the KABC-II will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the juvenile (Type 2) GM1 population and a secondary outcome measure for the infantile (Type 1) GM1 population.
Measured: Baseline through 36 months (3 years)
Change from baseline in the PedsQL total score
The Pediatric Quality of Life Inventory, Version 4.0 (PedsQL) is a 21 to 45-item assessment of quality of life over the previous 30 days, based on parent/caregiver report. The inventory consists of assessments for infants, toddlers, young children, children, teens and young adults, based on the age of the subject. A lower total score indicates higher quality of life.
Measured: Baseline through 36 months (3 years)
Change from baseline in attainment and/or retention of six World Health Organization motor development milestones
Motor development will be assessed in terms of six developmental milestones: sitting without support, standing with assistance, hands-and-knee crawling, walking with assistance, standing alone, and walking alone. Each milestone will be assessed as either "achieved", "not achieved" or "achieved but lost" based on clinician observation as well as parent report.
Measured: Baseline through 36 months (3 years)
Onset of and/or change in seizure activity over time
The change from baseline in presence/absence of seizures and frequency of seizures (if applicable) will be examined through review of seizure diaries recorded by parents over a three year period.
Measured: Baseline through 36 months (3 years)
Change from baseline ECG
An electrocardiogram (ECG) is a test using electrodes attached to the subject's chest, arms, and legs to record the electrical activity in the heart and detect abnormalities. The clinician will note whether each ECG is normal or abnormal, and the results will be compared to the baseline ECG and tracked over time.
Measured: Baseline through 36 months (3 years)
Change from baseline in bony structures of the spine using X-ray
A lateral spine plain film involves taking an X-ray of the subject's spine to determine if there are structural abnormalities. An X-ray of the spine will be performed at the baseline visit, then every 6 months for up to three years in order to assess changes.
Measured: Baseline through 36 months (3 years)
Change from baseline in ECHO parameters over time
An echocardiogram (ECHO) uses ultrasound to produce images of the subject's heart. The ECHO report will be evaluated for changes from baseline through the course of the study.
Measured: Baseline through 36 months (3 years)
Change from baseline EEG
An electroencephalogram (EEG) is a test using electrodes attached to the subject's scalp to detect abnormal activity in the brain. The EEG should be performed, if consent if provided, at each visit. The clinician will note whether each ECG is normal or abnormal, and the results will be compared to the baseline ECG and tracked over time.
Measured: Baseline through 36 months (3 years)
Change from baseline in brain volume and volume of substructures measured using MRI
If consent if provided, magnetic resonance imaging (MRI) of the brain will be obtained, without contrast, to examine changes in the total volume of the brain as well as the volumes of several brain substructures over time. The MRI may be performed under general anesthesia in this pediatric population. It is important that all procedures requiring general anesthesia are performed in close temporal proximity, while the subject is under anesthesia.
Measured: Baseline through 36 months (3 years)
Change from baseline in liver and spleen volume measured using MRI
If consent if provided, magnetic resonance imaging (MRI) of the abdomen will be obtained, without contrast, to examine changes in the total volume of the liver and spleen over time. The MRI may be performed under general anesthesia in this pediatric population. It is important that all procedures requiring general anesthesia are performed in close temporal proximity, while the subject is under anesthesia.
Measured: Baseline through 36 months (3 years)
Change from baseline in liver and spleen volume measured using ultrasound
Only if consent is not provided to obtain images of the abdomen via MRI, an abdominal ultrasound will be performed to examine changes in the total volume of the liver and spleen over time.
Measured: Baseline through 36 months (3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start12 Jun 2020
- Primary completion1 May 2024
- Study completion1 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GM1 GangliosidosisStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Passage Bio, Inc.
- Responsible party
- Sponsor
- Investigators
- Can Ficicioglu, MD, PhD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04041102
- Sponsor's protocol ID
- ODC-NHS-GM1-001-01
- Status last verified
- Oct 2025
- First submitted
- 16 Jul 2019
- Last updated
- 24 Oct 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 24 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients
- ClinicalTrials.gov ID
- NCT04041102
- Acronym / sponsor ID
- ODC-NHS-GM1-001-01
- Conditions
- GM1 Gangliosidosis
- Keywords
- GM1, GM1 gangliosidosis, GM1 Type 1, GM1 Type 2, GM1 gangliosidosis Type 1, GM1 gangliosidosis Type 2, GM1 natural history study, GM1 gangliosidosis natural history study
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Passage Bio, Inc.
- Study start
- 12 Jun 2020 (actual)
- Primary completion
- 1 May 2024 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 1 Aug 2019 (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.
Owing to the rarity, severity, speed of progression and fatal prognosis of infantile and juvenile GM1, there is a limited understanding of overall disease progression and meaningful outcome measures. This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of GM1 disease progression and clinical outcome. Having a GM1 natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials.
This natural history study will follow up to 40 subjects diagnosed with GM1 gangliosidosis (up to 20 infantile (Type 1) and 20 late infantile/juvenile (Type 2)) for up to 3 years. Visits will be conducted every 6 months, during which several procedures will be performed and the data recorded in order to learn about the natural course of the disease, including changes in clinical and neurological assessments and electrophysiologic, imaging and biofluid biomarkers. Study procedures include: physical \& neurological exam, blood \& urine sample collection, questionnaires \& assessments of development, seizure diary, ECHO, ECG, x-ray and ultrasound (if MRI not performed), EEG and genetic testing (if not already done).
The following procedures are subject to local/institutional policies and the medical discretion of the Study Physician: MRI, lumbar puncture (spinal tap) and General anesthesia/sedation (for MRI and LP).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infantile (Type 1) or Juvenile (Type 2) GM1 Gangliosidosis | – | –This study observes one cohort: up to 40 Infantile GM1 (Type 1) or Juvenile GM1 (Type 2) subjects. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals with a diagnosis of infantile (Type 1) or juvenile (Type 2) GM1 gangliosidosis.
Key inclusion criteria (5 listed)
- Documentation/ Confirmation of reduced beta-galactosidase enzyme activity in leukocytes
- Confirmed diagnosis of infantile or juvenile GM1 gangliosidosis with documentation of GLB1 mutations
- Parent/Caregiver capable of providing informed consent (if cognitively able, child to provide assent as well)
- Infantile (Type 1) GM1 subjects: Documented symptom onset by 6 months of age with significant hypotonia on exam or history elicited from parent(s)/ caregiver(s)
- Juvenile (Type 2) GM1 subjects: Documented symptom onset after 6 months of age OR documented symptom onset prior to 6 months of age without significant hypotonia on exam or elicited from parent(s)/ caregiver(s)
Key exclusion criteria (3 listed)
- Enrollment in any other clinical study with an investigational product/ therapy (patients receiving miglustat off-label will be eligible)
- Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or a secondary cause that may, in the opinion of the investigator, confound interpretation of study results
- Any condition that, in the opinion of the investigator, would put the subject at undue risk or make it unsafe for the subject to participate
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
Survival (Infantile GM1 population)
Time frame: Baseline through 36 months (3 years)
Survival will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Presence of and dependence on feeding tube (Infantile GM1 population)
Time frame: Baseline through 36 months (3 years)
The presence of a feeding tube and dependence on the feeding tube, if applicable, will be evaluated at the baseline visit and each subsequent visit for 3 years. This outcome measure is considered a primary outcome measure for the infantile (Type 1) GM1 population and a secondary outcome measure for the juvenile (Type 2) GM1 population.
Change from baseline in standard scores for each domain on the Vineland-II (Juvenile GM1 population)
Time frame: Baseline through 36 months (3 years)
The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is a standard assessment for measuring personal and social skills for children and adults (birth through 90 years of age). This assessment aids in diagnosis of intellectual and developmental disabilities or delays associated with a variety of diseases/disorders. The assessment includes 5 domains. Scores for each domain and a composite adaptive behavior score are then converted to standard scores with a range of 20 to 140, with a score of 140 correlating to a high adaptive level.
Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Juvenile GM1 population)
Time frame: Baseline through 36 months (3 years)
Based on the outcome of the Vineland-II, each subject will be given a developmental age score that will determine whether the Bayley Scale of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II) is administered. Children with a developmental age of 42 months or less will be administered the BSID-III and those with a developmental age of greater than 42 months will be administered the KABC-II. The BSID-III assesses 5 major areas of development. Each domain results in a raw score that is converted to a composite score. A higher composite score generally corresponds with higher function. The KABC-II assesses 4 major areas of intelligence and achievement in young children. Each domain results in a raw score that is converted to a standard score. Scores from 90-109 are generally considered average, with scores higher than 109 considered to be above average.
13 secondary outcomes
Survival (Juvenile GM1 population)
Time frame: Baseline through 36 months (3 years)
Presence of and dependence on feeding tube (Juvenile GM1 population)
Time frame: Baseline through 36 months (3 years)
Change from baseline in total score for each sub-domain of the BSID-III OR the KABC-II (Infantile GM1 population)
Time frame: Baseline through 36 months (3 years)
Change from baseline in the PedsQL total score
Time frame: Baseline through 36 months (3 years)
Change from baseline in attainment and/or retention of six World Health Organization motor development milestones
Time frame: Baseline through 36 months (3 years)
Onset of and/or change in seizure activity over time
Time frame: Baseline through 36 months (3 years)
Change from baseline ECG
Time frame: Baseline through 36 months (3 years)
Change from baseline in bony structures of the spine using X-ray
Time frame: Baseline through 36 months (3 years)
Change from baseline in ECHO parameters over time
Time frame: Baseline through 36 months (3 years)
Change from baseline EEG
Time frame: Baseline through 36 months (3 years)
Change from baseline in brain volume and volume of substructures measured using MRI
Time frame: Baseline through 36 months (3 years)
Change from baseline in liver and spleen volume measured using MRI
Time frame: Baseline through 36 months (3 years)
Change from baseline in liver and spleen volume measured using ultrasound
Time frame: Baseline through 36 months (3 years)
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 24 Oct 2025.
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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.
Can Ficicioglu, MD, PhD principal investigator
Children's Hospital of Philadelphia
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of GM1 Gangliosidosis, run by University of Pennsylvania at 6 sites in 5 countries.
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 5 inclusion and 3 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 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Brazil, Canada, Turkey (Türkiye), United Kingdom. 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?
Survival (Infantile GM1 population) (time frame: Baseline through 36 months (3 years)). The study lists 4 primary outcomes in all. 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 24 Oct 2025.