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

Primary Purpose

ALS

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ranolazine 500 MG
Ranolazine 1000 MG
Sponsored by
University of Kansas Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ALS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Kansas Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Ranolazine 500mg

Ranolazine 1000mg

Arm Description

Participants will take Ranolazine 500mg twice daily for up to 4 weeks.

Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Fasciculation frequency on muscle ultrasound
Count of fasciculation frequency in bilateral biceps, tibialis anterior, and gastrocnemius over 30 seconds
Cramp potential duration
Abductor hallucis brevis measured on EMG after supramaximal stimulation of posterior tibial nerve at 2 and 5 Hz

Full Information

First Posted
March 1, 2018
Last Updated
June 12, 2019
Sponsor
University of Kansas Medical Center
Collaborators
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03472950
Brief Title
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

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 11, 2018 (Actual)
Primary Completion Date
October 1, 2019 (Anticipated)
Study Completion Date
November 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Kansas Medical Center
Collaborators
Gilead Sciences

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ALS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ranolazine 500mg
Arm Type
Experimental
Arm Description
Participants will take Ranolazine 500mg twice daily for up to 4 weeks.
Arm Title
Ranolazine 1000mg
Arm Type
Experimental
Arm Description
Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Ranolazine 500 MG
Intervention Description
Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen).
Intervention Type
Drug
Intervention Name(s)
Ranolazine 1000 MG
Intervention Description
Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen).
Primary Outcome Measure Information:
Title
Dose limiting toxicities (DLT)
Description
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.
Time Frame
Up to Week 12
Secondary Outcome Measure Information:
Title
Cramp Questionnaire
Description
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.
Time Frame
Baseline, Weeks 2, 6, and 8
Title
Fasciculation frequency on muscle ultrasound
Description
Count of fasciculation frequency in bilateral biceps, tibialis anterior, and gastrocnemius over 30 seconds
Time Frame
Baseline, Weeks 2 and 6
Title
Cramp potential duration
Description
Abductor hallucis brevis measured on EMG after supramaximal stimulation of posterior tibial nerve at 2 and 5 Hz
Time Frame
Baseline, Weeks 2 and 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sherri Anderson
Phone
913-945-9936
Email
sanderson10@kumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Statland, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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