A Study of Ranolazine in ALS

Ranolazine in ALS: Safety, and Effect on Cramps, Function and Quality of Life.

The purpose of this study is to evaluate safety, effect on cramps, function and quality of life of ranolazine versus placebo for the treatment of ALS.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Ranolazine; Drug: Ranolazine; Drug: Placebo

Detailed Description

A prospective, multi center, double-blind, placebo-controlled, parallel group study of 2 doses of ranolazine (500 mg and 1000 mg twice daily) compared to placebo in patients with ALS.

Approximately 72 adults with ALS will be enrolled into the study in the United States at approximately 7 ALS treatment sites.

Participants will take oral ranolazine or placebo twice daily, attend a minimum of 5 onsite research visits, and 4 remote research visits.

The study is estimated to last 28 weeks for each participant.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Katie Lillig, BS; Phone Number: 913-945-9932; Email: Kjennens2@kumc.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Principal Investigator: Swathy Chandrashekhar, MD
      • Contact: Email: Neuromuscular.Research@ucsf.edu
      • Contact: Michael Han; Phone Number: 415-353-7381; Email: Michael.Han@ucsf.edu
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
      • Principal Investigator: Bjorn E Oskarsson, MD
      • Contact: Huy B. Tran; Phone Number: 904-953-4503; Email: Tran.Huy1@mayo.edu
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Medical Center
      • Principal Investigator: Jeffrey Statland, MD
      • Contact: Katie Lillig, BS; Phone Number: 913-945-9932; Email: Kjennens2@kumc.edu
      • Contact: Nick Staudenmier, BS; Phone Number: 913-945-9922; Email: nstaudenmier@kumc.edu
    • Wichita, Kansas, United States, 67214
      • Recruiting
      • University of Kansas Medical Center: Wichita
      • Contact: Hannah Hancock; Email: hhancock@kumc.edu
      • Contact: KUMC CTSU Wichita; Phone Number: 316-293-1833; Email: clinicaltrialunit@kumc.edu
      • Principal Investigator: Matthew Byerly, MD
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Recruiting
      • University of Missouri Health Care
      • Contact: Amanda Heider; Phone Number: 573-884-6852; Email: ahmc4@umsystem.edu
      • Principal Investigator: William D Arnold, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
      • Contact: Kaneshia Hives; Email: Kaneshia.Hives@osumc.edu
      • Principal Investigator: Sarah Heintzman, CNP
      • Contact: Atchayah Balakrishna; Email: Atchayah.Balakrishna@osumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older
• Diagnosed with clinically definite, possible, probably, or lab-supported probable ALS per revised El Escorial criteria
• Breathing assessment called forced vital capacity (FVC) greater than or equal to 50%.
• Able to swallow pills at the start of the study and expected to for the length of the study.
• If on ALS modifying medications must be on a stable dose at least 30 days.
• Experiencing 4 or more cramps per week during a 2-week screening period.

Exclusion Criteria:

• Disease duration < 5 years
• Tracheostomy invasive ventilation, or noninvasive ventilation of more than 12 hours/day
• Pregnant or lactating, adults unable to consent, and prisoners
• Taking ranolazine or investigational drug or has received an investigational drug within 30 days (or 5 half-lives for drugs, whichever is longer) prior to screening
• Medically uncontrolled comorbidities (heart, liver, kidney disease)
• Baseline QTc interval prolongation >450 ms for men/ >470 ms for women, history of long QT syndrome, or medications which prolong the QT interval
• Participation in an experimental drug trial less than 30 days before screening
• Patients have to be on a stable dosage of any medications used to treat muscle cramps for ≥30 days or have been off these medications ≥30 days prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranolazine low dose; Participants receive Ranolazine 500mg orally twice daily for 24 weeks.	Drug: Ranolazine; 500mg twice daily; Other Names: Ranexa; Drug: Ranolazine; 1000 mg twice daily; Other Names: Ranexa
Experimental: Ranolazine high dose; Participants receive Ranolazine 1000mg orally twice daily for 24 weeks.	Drug: Ranolazine; 500mg twice daily; Other Names: Ranexa; Drug: Ranolazine; 1000 mg twice daily; Other Names: Ranexa
Placebo Comparator: Placebo; Participants receive Ranolazine placebo orally twice daily for 24 weeks.	Drug: Placebo; Ranolazine placebo twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Treatment-Emergent Adverse Events	Patient report and medical records will be used to document adverse events and severe adverse events. Adverse events and severe adverse events will be assessed by the investigator and reported as needed for safety.	Up to 28 weeks
Tolerability of treatment assignment	Tolerability will be measured by percentage of patients who complete the treatment assignment. Dose limiting toxicities will be determined by individual with an adverse event necessitating stopping.	Up to 28 weeks
Muscle cramp frequency	Muscle cramp frequency will be measured numerically with a reporting period of 7 days. Changes will be compared from baseline to week 28 utilizing a modified Qualitative, Patient-Centered Assessment of Muscle Cramp Impact and Severity questionnaire.	Up to 28 weeks
Muscle cramp severity	Muscle cramp severity will be measured by a score of 1-10 (1 being a very mild muscle cramp and 10 being the most severe cramp you ever experienced). Changes will be compared from baseline to week 28 utilizing a modified Qualitative, Patient-Centered Assessment of Muscle Cramp Impact and Severity questionnaire.	Up to 28 weeks
Muscle cramps impact on quality of life	Effect of muscle cramps on quality of life will be measured with three patient reported yes or no questions (Yes indicating an impact on quality of life or no indicating no impact on quality of life). Changes will be compared from baseline to week 28 utilizing a modified Qualitative, Patient-Centered Assessment of Muscle Cramp Impact and Severity questionnaire	Up to 28 weeks
Safety Lab Cystatin C	Patient safety measured with lab value Cystatin C in mg/L.	Up to 28 weeks
Safety Lab Estimated Glomerular Filtration Rate (eGFR)	Patient safety measured with lab value eGFR in mL/min/1.73.	Up to 28 weeks
Safety Lab Alanine Transaminase (ALT)	Patient safety measured with lab value ALT in IU/L.	Up to 28 weeks
Safety Lab Aspartate Transferase (AST)	Patient safety measured with lab value AST in IU/L.	Up to 28 weeks
Safety Lab Alkaline Phosphatase (ALP)	Patient safety measured with lab value ALP in IU/L.	Up to 28 weeks
Safety Lab Total Bilirubin	Patient safety measured with lab value total bilirubin in mg/dL.	Up to 28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strength	Change in muscle strength over time as measured by hand grip and hand-held dynamometry (HHD) in pounds.	Up to 28 weeks
ALS Functional Rating Scale-Revised (ALSFRS-R)	Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function.	Up to 28 weeks
Forced Vital Capacity (FVC)	Change in respiratory function as measured by Forced Vital Capacity (FVC) in liters.	Up to 28 weeks
Serum neurofilament light	Changes in serum neurofilament light measured from baseline to end of treatment assignment. Data will be collected to determine differences between placebo and Ranolazine treatment groups at completion of the study.	Up to 28 weeks
Lymphocyte Mitochondrial Function	Change in mitochondrial function in lymphocytes measured from baseline to the end of treatment assignment. Data will be collected to determine differences between placebo and Ranolazine treatment groups at completion of the study	Up to 28 weeks

Collaborators and Investigators

• Sponsor: Swathy Chandrashekhar, MBBS
• Collaborators: ALS Association
• Investigators: Principal Investigator: Jeffrey Statland, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ALS; Motor Neuron Disease; Placebo-Controlled; Lou Gehrig's Disease
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Piperazines; Ranolazine
• Other Study ID Numbers: 24-43175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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