Clinical trial NCT03472950: Safety and Efficacy of Ranolazine for the Treatment of Amyotrophic Lateral Sclerosis
Official title: Safety and Efficacy of Ranolazine for the Treatment of Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ALS
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2018-03-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: Up to Week 12
Secondary outcomes:
measure: Percent Change in Cramp Frequency
timeFrame: Weekly for 12 weeks
measure: Percentage Change in Average Weekly Cramp Severity
timeFrame: Weekly for 12 weeks
measure: Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline
timeFrame: Weekly for 12 weeks
measure: Muscle Fasciculations Count
timeFrame: Up to week 12
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Jeffrey Statland, MD
role: PRINCIPAL_INVESTIGATOR
References: