- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01102686
Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)
February 22, 2012 updated by: The Hospital for Sick Children
Proposed Investigator-Initiated Clinical Trial of Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
20
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- The Hospital for Sick Children
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
17 years and older (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Pyrimethamine
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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
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of pyrimethamine
Time Frame: Baseline, before exposure to pyrimethamine, and Weeks 4, 8, 12, 16 and 18.
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Changes in Hex A and Hex B, β-glucuronidase using blood assays
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Baseline, before exposure to pyrimethamine, and Weeks 4, 8, 12, 16 and 18.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pyrimethamine Blood levels
Time Frame: Weekly (1-18 weeks)
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Weekly (1-18 weeks)
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Pyrimethamine efficacy
Time Frame: 6 months
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Measurement of GM2 in blood samples
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6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Joe T Clarke, MD, The Hospital for Sick Children
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2009
Primary Completion (ACTUAL)
November 1, 2010
Study Completion (ACTUAL)
November 1, 2010
Study Registration Dates
First Submitted
October 16, 2009
First Submitted That Met QC Criteria
April 12, 2010
First Posted (ESTIMATE)
April 13, 2010
Study Record Updates
Last Update Posted (ESTIMATE)
February 23, 2012
Last Update Submitted That Met QC Criteria
February 22, 2012
Last Verified
February 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Gangliosidoses
- Gangliosidoses, GM2
- Tay-Sachs Disease
- Sandhoff Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Protective Agents
- Micronutrients
- Vitamins
- Antiprotozoal Agents
- Antiparasitic Agents
- Antidotes
- Vitamin B Complex
- Antimalarials
- Folic Acid Antagonists
- Leucovorin
- Pyrimethamine
Other Study ID Numbers
- 1000013660
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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