A Study of Ranolazine in ALS
- Registration Number
- NCT06527222
- Lead Sponsor
- Swathy Chandrashekhar, MD
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants receive Ranolazine placebo orally twice daily for 24 weeks. Ranolazine low dose Ranolazine Participants receive Ranolazine 500mg orally twice daily for 24 weeks. Ranolazine high dose Ranolazine Participants receive Ranolazine 1000mg orally twice daily for 24 weeks.
- Primary Outcome Measures
Name Time Method Muscle cramp severity Up to 28 weeks 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.
Safety Lab Alanine Transaminase (ALT) Up to 28 weeks Patient safety measured with lab value ALT in IU/L.
Safety Lab Total Bilirubin Up to 28 weeks Patient safety measured with lab value total bilirubin in mg/dL.
Safety Lab Cystatin C Up to 28 weeks Patient safety measured with lab value Cystatin C in mg/L.
Tolerability of treatment assignment Up to 28 weeks 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.
Safety Lab Estimated Glomerular Filtration Rate (eGFR) Up to 28 weeks Patient safety measured with lab value eGFR in mL/min/1.73.
Safety Lab Aspartate Transferase (AST) Up to 28 weeks Patient safety measured with lab value AST in IU/L.
Muscle cramp frequency Up to 28 weeks 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.Frequency of Treatment-Emergent Adverse Events Up to 28 weeks 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.
Muscle cramps impact on quality of life Up to 28 weeks 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
Safety Lab Alkaline Phosphatase (ALP) Up to 28 weeks Patient safety measured with lab value ALP in IU/L.
- Secondary Outcome Measures
Name Time Method Muscle strength Up to 28 weeks Change in muscle strength over time as measured by hand grip and hand-held dynamometry (HHD) in pounds.
Serum neurofilament light Up to 28 weeks 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.
Forced Vital Capacity (FVC) Up to 28 weeks Change in respiratory function as measured by Forced Vital Capacity (FVC) in liters.
Lymphocyte Mitochondrial Function Up to 28 weeks 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
ALS Functional Rating Scale-Revised (ALSFRS-R) Up to 28 weeks 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.
Trial Locations
- Locations (7)
University of California, San Francisco
🇺🇸San Francisco, California, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
University of Kansas Medical Center
🇺🇸Fairway, Kansas, United States
University of Kansas Medical Center: Wichita
🇺🇸Wichita, Kansas, United States
University of Missouri Health Care
🇺🇸Columbia, Missouri, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States