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HSS Research Institute

Safety and Efficacy of SOD1 Inhibition by Pyrimethamine in Familial ALS

IRB Number: 29084
(inactive trial)

Institutional Review Board, Hospital for Special Surgery

July 07, 2010

The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.

Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.

For further information, see Understanding Clinical Trials.

Principal Investigator

Dale J. Lange, MD


40 patients with mild to moderate FALS and SOD1 mutations will receive up to 75 mg of pyrimethamine for a total of 36 weeks.  Following Screening and a 12-week titration period, patients will remain on up to 75 mg daily for 24 weeks.  This is an open label, single arm dose escalation study.

Inclusion/Exclusion Criteria

Inclusion Criteria

1. ALS diagnosed as probable, laboratory supported probable or definite according to the World Federation of Neurology El Escorial criteria [Brooks et al. 2000].
2. Age 18 or older.
3. Capable of providing informed consent and complying with trial procedures.
4. SOD1 mutation confirmation by study team.
5. Not taking Riluzole (Rilutek) or on a stable dose for 30 days.
6. Not taking Coenzyme QR10R or on a stable dose and brand for 30 days.
7. Absence of exclusion criteria.

Exclusion Criteria

1. History or evidence of malabsorption syndromes.
2. Exposure to any experimental agent within 30 days of onset of this protocol.
3. Women who are pregnant or planning to become pregnant.
4. Women of childbearing potential not practicing contraception.
5. Women who are breastfeeding.
6. Enrollment in another research study within 30 days of or during this trial.
7. Alcoholism.
8. Patients taking phenytoin (Dilantin) or other therapy affecting folate levels.
9. Dementia (MMSE <22).
10. Seizure disorder.
11. Folate deficiency.
12. Megaloblastic anemia.
13. Cardiovascular disorder/arrhythmia.
14. Impaired kidney function, defined as creatinine levels of 2.5 x ULN.
15. Impaired liver function, defined as AST or ALT of 3 X ULN.
16. Advanced ALS patients, defined as those with any of the following: forced vital capacity <60% (use of BIPAP is allowed); traecheostomy; or mechanical ventilation.
17. Use of any of the following medications: cytosine, arabinoside, methotrexate, daunorubicin, sulfonamides, zidovudine, lorazapam, coumadin, sulfamethoxazole, and trimethoprim.
18. Patients taking Lithium within 30 days of or during this trial.
19. Incapable of providing informed consent and complying with trial procedures.

Contact Information

Nicole Kassebaum, MS
Clinical Research Coordinator
Neurology Department
Hospital for Special Surgery
Tel: 646.797.8592
Fax: 646.797.8942