A Study of Ranolazine in ALS

NCT06527222 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-43175
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 7

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Motor Neuron Disease; Lou Gehrig's Disease; Placebo-Controlled

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (5)

• Muscle strength

  Up to 28 weeks

• ALS Functional Rating Scale-Revised (ALSFRS-R)

  Up to 28 weeks

• Forced Vital Capacity (FVC)

  Up to 28 weeks

• Serum neurofilament light

  Up to 28 weeks

• Lymphocyte Mitochondrial Function

  Up to 28 weeks

Study Arms (3)

Ranolazine low dose

EXPERIMENTAL

Participants receive Ranolazine 500mg orally twice daily for 24 weeks.

Drug: Ranolazine

Ranolazine high dose

EXPERIMENTAL

Participants receive Ranolazine 1000mg orally twice daily for 24 weeks.

Drug: Ranolazine

Placebo

PLACEBO COMPARATOR

Participants receive Ranolazine placebo orally twice daily for 24 weeks.

Drug: Placebo

Interventions

Ranolazine DRUG

500mg twice daily

Also known as: Ranexa

Ranolazine low dose

Placebo DRUG

Ranolazine placebo twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swathy Chandrashekhar, MBBS: lead
• ALS Association: collaborator

Study Sites (7)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

RECRUITING

University of Kansas Medical Center: Wichita

Wichita, Kansas, 67214, United States

RECRUITING

University of Missouri Health Care

Columbia, Missouri, 65212, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

National Neuromuscular Research Institute, PLLC.

Austin, Texas, 78759, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey Statland, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katie Lillig, BS

CONTACT

913-945-9932; Kjennens2@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: July 30, 2024
• Study Start: April 29, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: October 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)