Safety and Efficacy of Ranolazine for the Treatment of Amyotrophic Lateral Sclerosis

Full Study Summary:

Amyotrophic Lateral Sclerosis (ALS) is a progressive debilitating and fatal neurodegenerative disease involving the motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord with 5,000 newly diagnosed patients per year in the USA. There is a pressing need for additional therapies, as the only two FDA-approved drugs for ALS, riluzole and edaravone, showed prolongation of median survival of only two to three months and only a modest benefit in daily functioning, respectively. The ability to identify FDA approved drugs which can be repurposed to ALS, and which may slow disease progression, alleviate symptoms, or prolong survival will have an immediate positive impact of the lives of patients with ALS and their family members. Hypothesis: Ranolazine, an FDA approved drug for angina which inhibits the late Na+ current and intracellular Ca2+ accumulation may be neuroprotective in ALS by reducing neuronal hyperexcitability, may slow disease progression and reduce cramp frequency.

• Eligibility Criteria

  Gender:

  Female, Male

  Minimum Age:

  18

  Maximum Age:

  N/A

  Time since Symptom Onset:

  Time since Diagnosis:

  Can participants use Riluzole?

  Yes

  
  

  Inclusion Criteria:

  Patients with clinically definite, probable, laboratory supported probable, or possible ALS per revised El Escorial criteria
  Cramp frequency greater than 4 cramps per week during 2 week run in
  ALS functional rating scale-revised (ALSFRS-R) score of greater than 24
  Able to lie on back for study procedures

  Exclusion Criteria:

  Tracheostomy invasive ventilation, or use of non-invasive ventilation greater than 12 hours per day
  Pregnant or lactating
  Participation in a prior experimental drug trial less than 30 days prior to screening
  Patients taking ranolazine
  Patients taking medications which are contraindicated for use with ranolazine such as strong CYP3 inhibitors (ketoconazole, clarithromycin, nelfinavir), and CYP3 inducers (rifampin, phenobarbital)
  Patients with clinically significant medical comorbidities (hepatic, renal, cardiac, etc)
  Patients with baseline QT interval prolongation on Electrocardiography (ECG)
  Patients pre-disposed to secondary QT prolongation for other health conditions like family history of congenital long QT syndrome, heart failure, bradycardia, or cardiomyopathies

• Site Contact Information

  University of Kansas Medical Center
  Kansas City, Kansas 66160
  United States