Status:
WITHDRAWN
A Phase I Study of Pyrimethamine in Patients With GM2 Gangliosidosis
Lead Sponsor:
Exsar Corporation
Collaborating Sponsors:
University Hospitals Cleveland Medical Center
NYU Langone Health
Conditions:
G(M2) Ganglioside
Tay-Sachs Disease Ganglioside
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
Adult Tay-Sachs disease and Sandhoff diseases are caused by deficiency of an enzyme called β-hexosaminidase A, or Hex A in short. This enzyme is located in a particular cellular component, called lyso...
Detailed Description
Adult Tay-Sachs (TSD) and Sandhoff disease (SD) result from a deficiency of lysosomal heterodimeric β-hexosaminidase A (Hex A, αβ). These disorders are characterized by progressive neurological deteri...
Eligibility Criteria
Inclusion
- Biochemically and genetically confirmed diagnosis of GM2 Gangliosidosis caused by β-hexosaminidase deficiency resulting from mutations in the HEX-A or HEX-B genes, which has been shown to respond to Pyrimethamine treatment in previous cell culture experiments (Maegawa et al. 2006).
- Must be 18 years of age or older to participate in the study.
- Able to understand and cooperate with the requirements of the study protocol.
- Mentally competent, have ability to understand and willingness to sign the informed consent form.
- Able to travel to the participating study site.
- Women of child-bearing potential must use accepted contraceptive methods, and must have a negative serum or urine pregnancy test within 2 days 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 be within acceptable range.
- Body weight \>40 kg (88 pounds).
Exclusion
- Serious medical illness, significant cardiac disease that would increase patients' risk for toxicity.
- Any hematologic or related abnormality, especially megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, atrophic glossitis, hematuria, and disorders of cardiac rhythm, pulmonary eosinophilia, etc.
- Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease).
- Possible folate deficiency, such as individuals with malabsorption syndrome, alcoholism, or pregnancy, 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 (because Pyrimethamine is a "Pregnancy Category C" product).
- Lactating females because of the potential for serious adverse reactions in nursing infants.
- 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 or to the inactive ingredients (corn and potato starch, lactose, and magnesium stearate).
- Evidence of systemic infection, or anyone who in the opinion of the investigator would not be suitable for the study.
- Test positive for HIV.
- Test positive for hepatitis B or hepatitis C.
- Patients with a history of convulsive disorders, since these patients are very susceptible to the nervous system toxicity of Pyrimethamine.
- Patients receiving any other investigational treatment for any indication within the past 4 weeks prior to initiation of Pyrimethamine treatment.
- A history of cancer of any type, since Pyrimethamine may be carcinogenic.
- Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of Pyrimethamine treatment.
- Patients who are receiving antifolic drugs and drugs associated with myelosuppression, or patients who are receiving drugs, when used in combination with Pyrimethamine, have been reported to induce some degree of hepatotoxicity:
- Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
Key Trial Info
Start Date :
May 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT00679744
Start Date
May 1 2008
Last Update
February 25 2013
Active Locations (3)
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1
New York University, School of Medicine, Department of Neurology
New York, New York, United States, 10016
2
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
3
Division of Clinical & Metabolic Genetics, Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8