A Natural History of Late Onset Tay-Sachs Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02851862
Recruitment Status : Active, not recruiting
First Posted : August 2, 2016
Last Update Posted : June 20, 2018
Information provided by (Responsible Party):
Florian Eichler, Massachusetts General Hospital

Brief Summary:
The purpose of this study is to learn more about the natural history of Late Onset GM2 Gangliosidosis (Tay-Sachs disease and Sandhoff Disease) to inform future clinical trials.

Condition or disease
GM2 Gangliosidosis

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Detailed Description:

For this study, subjects will come to Massachusetts General Hospital for two study visits, six months apart. At each visit, the following tests will be done:

A Neurological Exam, Several Ataxia Rating Scales, A Formal Speech assessment, Magnetic resonance imaging and spectroscopy, A blood draw, An optional lumbar puncture.

Outcome measures and biomarkers (MRI atrophy measures, chemical shift imaging (CSI), MRS and CSF metabolites) will be compared to the clinical disease course in Late Onset GM2 Gangliosidosis. The natural history by retrospective surveys (previously acquired) will shed light on how changes in outcome measures compare to the larger context of changing symptoms (that occurs on the scale of years and decades). This combined approach will elucidate optimal outcome measures and determine eligibility criteria for a future clinical trial in Late Onset GM2 Gangliosidosis.

The international web-based platform for clinical research networks, NeuroBANK™, in which clinicians and researchers collect and share their patients' clinical and research data, will be used. This system has been implemented by and deployed at the Neurological Clinical Research Institute at Massachusetts General Hospital. This platform allows clinicians to enter patient data, either a) manually via a Web-based interface, or b) by exporting the data from the electronic health record (EHR) and clinical data repositories.


A patient Global Unique Identifier (GUID) will be used as the identifier for individuals participating in the study in NeuroBANK™. The GUID is an 11-character string that is generated using encryption technology and algorithms licensed by the NCRI from the National Institutes of Health (NIH).

The GUID is generated on a secure website that utilizes 128-bit Secure Socket Layer (SSL). Of note, this website is not linked to NeuroBANK™. The GUID is generated using an irreversible encryption algorithm - it accepts twelve identifying data elements, (e.g. last name at birth, first name at birth, gender at birth, day, month and year of birth, city and country of birth, etc.), and produces a unique random-generated character string, or GUID. No identifying information is stored in the system; it is simply used to generate the GUID. If the same information is entered again, the same GUID will be returned.

The GUID is entered into NeuroBANK™ when the patient is being created in the system. As the same patient may participate in multiple studies, NeuroBANK™ will also allow capturing a study-specific ID for the patient. For more information about NeuroBANK™ or the GUID, please go to:

Data Management:

The NCRI Data Management Team is trained and knowledgeable regarding confidentiality and integrity of data. They will be responsible for all aspects of data procedures. Alex Sherman is the ALD Connect network strategist and member of the NEALS ALS consortium. He is the director of Strategic Development and Systems of NCRI, serves on the Executive Committee of the ALS Research Group, and is one of the leaders of the NEALS ALS Consortium.

Data Quality Checks, Logic Checks and Queries:

The Data Manager (DM) at the Neurological Clinical Research Institute (NCRI) at the Massachusetts General Hospital will conduct monthly Data Quality Checks, Logic Checks, and internal data quality audits. Data field queries will be resolved in an established workflow according to the Standard Operating Procedures (SOPs). The queries may be created either at the point of entry during the data entry process, manually by the NCRI DM, or as the result of executing monthly Logic Checks.

Study-Specific Database Backup and Maintenance:

The NCRI personnel will be responsible for the database backups that will be conducted daily. Simultaneously, a separate copy of the backup in the encrypted compressed format will be maintained and saved by the System Analysts. The backups will be saved on a separate computer partition in a password-protected compressed format and also will be burnt into DVD medium and stored in a secure location.

Study Type : Observational [Patient Registry]
Estimated Enrollment : 10 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 6 Months
Official Title: A Natural History of Late Onset Tay-Sachs Disease: MGH Site
Study Start Date : April 2016
Actual Primary Completion Date : April 2018
Estimated Study Completion Date : April 2019

Late Onset GM2 Gangliosidosis
10-15 subjects with Late Onset GM2 Gangliosidosis

Primary Outcome Measures :
  1. Change in Brief Ataxia Rating Scale over six months [ Time Frame: baseline and 6 month visits ]
    Ataxia rating scale incorporating gait, dysarthria, and coordination

Secondary Outcome Measures :
  1. Change over six months in metabolite levels seen on magnetic resonance spectroscopy [ Time Frame: baseline and 6 months ]
  2. Change over six months in lipid levels found in the cerebrospinal fluid [ Time Frame: baseline and 6 months ]

Biospecimen Retention:   Samples With DNA
Blood will be collected to establish lymphoblast cell lines. Cerebrospinal fluid will also be collected from some subjects.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects diagnosed with Late Onset GM2 Gangliosidosis

Inclusion Criteria:

  • The subject must have a confirmed diagnosis of Late Onset GM2 Gangliosidosis as defined by (a) absent to near-absent beta-hexosaminidase enzymatic activity in the serum or white blood cells or (b) mutation analysis of the HEXA and HEXB genes to distinguish pseudo deficiency alleles from disease-causing alleles
  • The subject must be older than 7 years of age

Exclusion Criteria:

  • If a patient is very severely affected by the disease, the PI will assess whether it is in the best interest of the patient to exclude them from the study for their own comfort and well being. In cases where the PI deems it appropriate, severely affected patients will be excluded. Patients under the age of 7 years will be excluded from this study.

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 identifier (NCT number): NCT02851862

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Principal Investigator: Florian Eichler, MD Massachusetts General Hospital

Responsible Party: Florian Eichler, Director of the Center for Rare Neurological Diseases, Massachusetts General Hospital Identifier: NCT02851862     History of Changes
Other Study ID Numbers: 2015P002399
First Posted: August 2, 2016    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data from this study will be stored in a computer data repository at the Massachusetts General Hospital (MGH) Neurological Clinical Research Institute (NCRI). The purpose of this data repository is to capture and store data for clinical research. The repository will combine data from multiple studies. Datasets will be shared with researchers who want to advance understanding of Neurological Disease. These datasets will not contain any personal identifiable information.

Additional relevant MeSH terms:
Tay-Sachs Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Gangliosidoses, GM2
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors