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

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.

Study Overview

• Status: Unknown
• Conditions: ALS
• Intervention / Treatment: Drug: Ranolazine 500 MG; Drug: Ranolazine 1000 MG

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sherri Anderson; Phone Number: 913-945-9936; Email: sanderson10@kumc.edu

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ranolazine 500mg; Participants will take Ranolazine 500mg twice daily for up to 4 weeks.	Drug: Ranolazine 500 MG; Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen).
EXPERIMENTAL: Ranolazine 1000mg; Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.	Drug: Ranolazine 1000 MG; Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities (DLT)	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.	Up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cramp Questionnaire	The cramp questionnaire asks if a person has experienced cramps in last week, how many total, whether they occur daily, how long they last on average (seconds - minutes), locations (body region). Responses measure average severity on a scale from 1-9. A score of 1 being mild and score of 9 being worst ever experienced.	Baseline, Weeks 2, 6, and 8
Fasciculation frequency on muscle ultrasound	Count of fasciculation frequency in bilateral biceps, tibialis anterior, and gastrocnemius over 30 seconds	Baseline, Weeks 2 and 6
Cramp potential duration	Abductor hallucis brevis measured on EMG after supramaximal stimulation of posterior tibial nerve at 2 and 5 Hz	Baseline, Weeks 2 and 6

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2018
• Primary Completion (ANTICIPATED): October 1, 2019
• Study Completion (ANTICIPATED): November 1, 2019

Study Registration Dates

• First Submitted: March 1, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (ACTUAL): March 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: STUDY00141491

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No