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Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease) | Clinical Trials | Clareo Health

COMPLETEDPHASE1/PHASE2

Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

Proposed Investigator-Initiated Clinical Trial of Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

NCT01102686•The Hospital for Sick Children

View on ClinicalTrials.gov

Summary

The objectives of this clinical trial are to assess the safety and tolerability, as well as efficacy, of a stepwise dosing regimen of pyrimethamine, starting at 25 mg/day, given as a single dose daily for 4 weeks in patients affected with chronic Tay-Sachs or Sandhoff variants.

Detailed Description

Patients with late-onset Tay-Sachs or Sandhoff disease will be given increasing doses of Pyr, up to but not exceeding doses used to treat malaria, over a 5-month period. We will follow the effect of the treatment on the levels of Hex A enzyme activity in white blood cells, which are considered to be a reflection of the likely enzyme activity in the brain. We will also follow some other lysosomal enzyme activities to determine if the effect is specific for Hex A. Furthermore, we will examine the effect of the treatment on the levels of GM2-ganglioside in the white blood cells. On the basis of the studies done on cultured skin cells, we expect that treatment with Pyr will increase the levels of Hex A and decrease the accumulation of GM2-ganglioside in the white blood cells.

Eligibility

Age

17 - No limit years

Sex

ALL

Healthy Volunteers

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;
+5 more criteria

Locations (1)

The Hospital for Sick Children

Toronto, Ontario, Canada

Key Dates

Start Date

August 1, 2009

Primary Completion Date

November 1, 2010

Completion Date

November 1, 2010

Last Updated

February 23, 2012

Enrollment

ESTIMATED participants

Conditions

Gangliosidoses, GM2Sandhoff DiseaseTay-Sachs Disease

Interventions

Pyrimethamine

DRUG

Leucovorin

DRUG

A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of GM1 Gangliosidosis or GM2 Gangliosidosis

NCT07082543

Gangliosidoses, GM2Gangliosidosis, GM1

View study

RECRUITINGPHASE1

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

NCT02254863

AdrenoleukodystrophyBatten Disease+10 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 23, 2012Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

Inclusion Criteria

Exclusion Criteria

A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of GM1 Gangliosidosis or GM2 Gangliosidosis

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

Long-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease

A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease

Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

Synergistic Enteral Regimen for Treatment of the Gangliosidoses