Clinical Research Directory

Inclusion Criteria: 1. Non-smoking adults aged 21-80 years will be eligible to participate. \- Upon screening, eligible patients will have an 2. ALS diagnosis (El Escorial diagnostic classifications of probable/definite ALS), 3. vital capacity (VC) \> 60% of predicted value, and 4. ALS Functional Rating Scale (ALSFRS-R) scores of 2 or greater for bulbar and respiratory items: swallowing, speech, salivation, dyspnea, orthopnea, and respiratory insufficiency. 5. Additionally, patients taking riluzole and/or edaravone must be on a stable dose for \>30 days. 6. Unaffected control subjects will be eligible if they have a vital capacity (VC) \> 60% of predicted value. Exclusion Criteria: Patient and control are ineligible if they 1. are pregnant 2. have an active respiratory infection, 3. took antibiotics within 4 weeks, 4. are diagnosed with another neurodegenerative disease, 5. have symptomatic cardiovascular disease or dysrhythmias (resting tachycardia and hypertension), 6. exhibit history or presence of hypoxemia or hypercapnia, 7. presence of rest tachypnea (RR ˃30), 8. have a BMI \>35 kg/m2, 9. have a seizure disorder, 10. take respiratory inhalers daily for airway disease, or 11. require external respiratory support while awake and upright, or 12. supplemental oxygen at rest or at night. 13. In addition, the following conditions are exclusionary for the use of istradefylline: routine use of CYP3A4 inducers (i.e. carbamazepine, phenobarbitol, rifampin, phenytoin, St. John's Wort, glucocorticoids) or 14. medications that may suppress ventilation, history of moderate renal impairment or severe hepatic impairment, and history of hallucinations or psychosis. 15. Patients who cannot safety swallow thin liquids (required for administration of istradefylline and placebo) will also be ineligible.