A Study of Ranolazine in ALS

Phase 2RecruitingNCT06527222

Swathy Chandrashekhar, MBBS72 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Amyotrophic Lateral Sclerosis

Interventions

RanolazineDRUG

500mg twice daily

RanolazineDRUG

1000 mg twice daily

PlaceboDRUG

Ranolazine placebo twice daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (7)

University of California, San Francisco

San Francisco, California, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, United States

RECRUITING

University of Kansas Medical Center

Fairway, Kansas, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: Up to 28 weeks

Safety Lab Cystatin C

Patient safety measured with lab value Cystatin C in mg/L.

Central Contacts

Katie Lillig, BS

CONTACT

913-945-9932 Kjennens2@kumc.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Muscle strength

Change in muscle strength over time as measured by hand grip and hand-held dynamometry (HHD) in pounds.

Time frame: 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.

Time frame: Up to 28 weeks

Forced Vital Capacity (FVC)

Change in respiratory function as measured by Forced Vital Capacity (FVC) in liters.

Time frame: 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.

Time frame: 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

Time frame: Up to 28 weeks