Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Motor Neuron Disease, Lou Gehrig's Disease, Placebo-Controlled
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.
Interventions
DRUGRanolazine
500mg twice daily
DRUGPlacebo
Ranolazine placebo twice daily
Sponsors
Swathy Chandrashekhar, MBBS
ALS Association
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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 Cystatin C | Up to 28 weeks | Patient safety measured with lab value Cystatin C in mg/L. |
| 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 Alanine Transaminase (ALT) | Up to 28 weeks | Patient safety measured with lab value ALT in IU/L. |
| Safety Lab Aspartate Transferase (AST) | Up to 28 weeks | Patient safety measured with lab value AST in IU/L. |
| Safety Lab Alkaline Phosphatase (ALP) | Up to 28 weeks | Patient safety measured with lab value ALP in IU/L. |
| Safety Lab Total Bilirubin | Up to 28 weeks | Patient safety measured with lab value total bilirubin in mg/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle strength | Up to 28 weeks | Change in muscle strength over time as measured by hand grip and hand-held dynamometry (HHD) in pounds. |
| 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. |
| Forced Vital Capacity (FVC) | Up to 28 weeks | Change in respiratory function as measured by Forced Vital Capacity (FVC) in liters. |
| 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. |
| 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 |
Countries
United States
Contacts
CONTACTKatie Lillig, BS
PRINCIPAL_INVESTIGATORJeffrey Statland, MD
University of Kansas Medical Center
Outcome results
None listed