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

ALS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03472950
• Other study ID #: STUDY00141491
• Status: Recruiting
• Phase: Phase 2
• Start date: June 11, 2018
• Est. completion date: November 1, 2019

Study information

• Verified date: June 2019
• Source: University of Kansas Medical Center
• Contact: Sherri Anderson
• Phone: 913-945-9936
• Email: sanderson10[@]kumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

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).
• 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).

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Kansas Medical Center	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Fasciculation frequency on muscle ultrasound	Count of fasciculation frequency in bilateral biceps, tibialis anterior, and gastrocnemius over 30 seconds	Baseline, Weeks 2 and 6
Secondary	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