Clinical trial: SOD1 Inhibition by Pyrimethamine in Familial Amyotrophic Lateral Sclerosis (ALS) (NCT01083667)

Eligibility criteria:
Inclusion Criteria:

          -  Subjects with definite, probable, or laboratory supported probable ALS will be
             eligible.

               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); tracheostomy; or mechanical ventilation

         17. Use of any of the following medications: cytosine, arabinoside, methotrexate,
             daunorubicin, sulfonamides, zidovudine, lorazepam, 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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? Contradiction