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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03472950
Recruitment Status : Recruiting
First Posted : March 21, 2018
Last Update Posted : June 13, 2019
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Jeffrey Statland, University of Kansas Medical Center

Tracking Information
First Submitted Date  ICMJE March 1, 2018
First Posted Date  ICMJE March 21, 2018
Last Update Posted Date June 13, 2019
Actual Study Start Date  ICMJE June 11, 2018
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
Dose limiting toxicities (DLT) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03472950 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Cramp Questionnaire [ Time Frame: Baseline, Weeks 2, 6, and 8 ]
    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.
  • Fasciculation frequency on muscle ultrasound [ Time Frame: Baseline, Weeks 2 and 6 ]
    Count of fasciculation frequency in bilateral biceps, tibialis anterior, and gastrocnemius over 30 seconds
  • Cramp potential duration [ Time Frame: Baseline, Weeks 2 and 6 ]
    Abductor hallucis brevis measured on EMG after supramaximal stimulation of posterior tibial nerve at 2 and 5 Hz
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
  • Cramp Questionnaire [ Time Frame: Week 6 ]
    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.
  • Fasciculation frequency [ Time Frame: Week 6 ]
  • Cramp potential duration [ Time Frame: Change from Baseline to Week 6 ]
  • Cramp Questionnaire [ Time Frame: Week 8 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Ranolazine for the Treatment of Amyotrophic Lateral Sclerosis
Official Title  ICMJE Safety and Efficacy of Ranolazine for the Treatment of Amyotrophic Lateral Sclerosis
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE ALS
Intervention  ICMJE
  • 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).
  • 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).
Study Arms  ICMJE
  • Experimental: Ranolazine 500mg
    Participants will take Ranolazine 500mg twice daily for up to 4 weeks.
    Intervention: Drug: Ranolazine 500 MG
  • Experimental: Ranolazine 1000mg
    Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.
    Intervention: Drug: Ranolazine 1000 MG
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2019
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sherri Anderson 913-945-9936 sanderson10@kumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03472950
Other Study ID Numbers  ICMJE STUDY00141491
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jeffrey Statland, University of Kansas Medical Center
Study Sponsor  ICMJE University of Kansas Medical Center
Collaborators  ICMJE Gilead Sciences
Investigators  ICMJE
Principal Investigator: Jeffrey Statland, MD University of Kansas Medical Center
PRS Account University of Kansas Medical Center
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP