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

Phase 2

Completed

Brief Summary: The purpose of this research study is to evaluate the safety and effectiveness of Ranolazine, and how well it is tolerated in patients with Amyotrophic Lateral Sclerosis (ALS). Ranolazine is an FDA approved drug that is used for decreasing chest pain.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Ranolazine 500mg	Ranolazine 500 MG	Participants will take Ranolazine 500mg twice daily for up to 4 weeks.
Ranolazine 1000mg	Ranolazine 1000 MG	Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicities (DLT)	Up to Week 12	Measured as any drug-related serious adverse event, or drug-related adverse event necessitating study withdrawal. If a dose has less than 33% DLTs it will be considered tolerable.

Secondary Outcome Measures

Name	Time	Method
Percent Change in Cramp Frequency	Weekly for 12 weeks	The percent change in cramp frequency: average daily cramp frequency, comparing week 12-baseline
Percentage Change in Average Weekly Cramp Severity	Weekly for 12 weeks	Percent change in average weekly cramp severity (1 being a very mild muscle cramp and 10 being the most severe cramp you ever experienced)
Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline	Weekly for 12 weeks
Muscle Fasciculations Count	Up to week 12