Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff 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. |
ClinicalTrials.gov Identifier: NCT01102686 |
Recruitment Status
:
Completed
First Posted
: April 13, 2010
Last Update Posted
: February 23, 2012
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Gangliosidoses, GM2 Sandhoff Disease Tay-Sachs Disease | Drug: Pyrimethamine Drug: Leucovorin | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 20 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Proposed Investigator-Initiated Clinical Trial of Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease) |
Study Start Date : | August 2009 |
Actual Primary Completion Date : | November 2010 |
Actual Study Completion Date : | November 2010 |

Arm | Intervention/treatment |
---|---|
Experimental: Pyrimethamine |
Drug: Pyrimethamine
Pyrimethamine will be taken orally as a single daily dose of 25 mg/day for 4 weeks, then increasing by 25 mg per dose in three four-week steps, to a final dose of 100 mg/day
Drug: Leucovorin
To eliminate or minimize potential hematologic effects of Pyrimethamine, Leucovorin is to be co-administered with Pyrimethamine at a dose level of 5 mg per day, given when Pyrimethamine is administered.
|
- Efficacy of pyrimethamine [ Time Frame: Baseline, before exposure to pyrimethamine, and Weeks 4, 8, 12, 16 and 18. ]Changes in Hex A and Hex B, β-glucuronidase using blood assays
- Pyrimethamine Blood levels [ Time Frame: Weekly (1-18 weeks) ]
- Pyrimethamine efficacy [ Time Frame: 6 months ]Measurement of GM2 in blood samples

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: | 17 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- biochemically and genetically confirmed diagnosis of GM2-gangliosidosis caused by β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes;
- having HEXA or HEXB mutations shown to be responsive to pyrimethamine in vitro;
- over 17 years of age at the time of study initiation;
- able to understand and cooperate with the requirements of the study protocol;
- mentally competent, have the ability to understand and willingness to sign the informed consent form;
- able to travel to one of the three participating study sites;
- women of child-bearing potential must use accepted contraceptive methods and must have a negative serum or urine pregnancy test within one week prior to treatment initiation;
- fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists;
- laboratory values ≤2 weeks prior to randomization must show adequate hematologic, hepatic, renal, and coagulation function; and body weight >40 kg.
Exclusion Criteria:
- serious medical illness, significant cardiac disease or severe debilitating pulmonary disease;
- any hematologic abnormality, especially megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia;
- any active uncontrolled bleeding or any bleeding diathesis (e.g., active peptic ulcer disease);
- possible folate deficiency, and those receiving therapy (such as phenytoin) affecting folate levels;
- any complex disease that may confound treatment assessment;
- pregnant women or women of child-bearing potential not using reliable means of contraception;
- lactating females;
- fertile men unwilling to practice contraceptive methods during the study period;
- unwilling or unable to follow protocol requirements;
- known hypersensitivity reactions, intolerance or adverse reactions to pyrimethamine;
- evidence of active infection, or serious infection within the past month;
- HIV infection;
- a history of cancer of any type;
- receiving any other standard or investigational treatment for any indication within the past 4 weeks prior to initiation of pyrimethamine treatment;
- receiving immunotherapy of any type within the past 4 weeks prior to initiation of pyrimethamine treatment; or any condition or abnormality, which may, in the opinion of the investigator, compromise the safety of patients.

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): NCT01102686
Canada, Ontario | |
The Hospital for Sick Children | |
Toronto, Ontario, Canada, M5G 1X8 |
Principal Investigator: | Joe T Clarke, MD | The Hospital for Sick Children |
Responsible Party: | The Hospital for Sick Children |
ClinicalTrials.gov Identifier: | NCT01102686 History of Changes |
Other Study ID Numbers: |
1000013660 |
First Posted: | April 13, 2010 Key Record Dates |
Last Update Posted: | February 23, 2012 |
Last Verified: | February 2012 |
Keywords provided by The Hospital for Sick Children:
Late-onset GM2-gangliosidosis pyrimethamine |
Additional relevant MeSH terms:
Tay-Sachs Disease Gangliosidoses Sandhoff Disease Gangliosidoses, GM2 Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn |
Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Pyrimethamine Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |