NCT01102686

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)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: The Hospital for Sick Children · Academic / Other
• Sex: All
• Age: 17 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Gangliosidoses, GM2
• Sandhoff Disease
• Tay-Sachs Disease

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2009-08-01
• Primary completion: 2010-11-01
• Completion: 2010-11-01
• First posted: 2010-04-13
• Last updated: 2012-02-23

Locations

1 site across 1 country: Canada