Ranolazine in ALS: Safety, and Effect on Cramps, Function and Quality of Life.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 13
- 主要终点
- Safety Lab Alanine Transaminase (ALT)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Participants receive Ranolazine placebo orally twice daily for 24 weeks.
干预措施: Placebo (Drug)
Ranolazine low dose
Participants receive Ranolazine 500mg orally twice daily for 24 weeks.
干预措施: Ranolazine (Drug)
Ranolazine high dose
Participants receive Ranolazine 1000mg orally twice daily for 24 weeks.
干预措施: Ranolazine (Drug)
结局指标
主要结局
Safety Lab Alanine Transaminase (ALT)
时间窗: Up to 28 weeks
Patient safety measured with lab value ALT in IU/L.
Safety Lab Total Bilirubin
时间窗: Up to 28 weeks
Patient safety measured with lab value total bilirubin in mg/dL.
Safety Lab Cystatin C
时间窗: Up to 28 weeks
Patient safety measured with lab value Cystatin C in mg/L.
Tolerability of treatment assignment
时间窗: 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 severity
时间窗: 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 Estimated Glomerular Filtration Rate (eGFR)
时间窗: Up to 28 weeks
Patient safety measured with lab value eGFR in mL/min/1.73.
Safety Lab Aspartate Transferase (AST)
时间窗: Up to 28 weeks
Patient safety measured with lab value AST in IU/L.
Frequency of Treatment-Emergent Adverse Events
时间窗: 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 cramp frequency
时间窗: 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 cramps impact on quality of life
时间窗: 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)
时间窗: Up to 28 weeks
Patient safety measured with lab value ALP in IU/L.
次要结局
- Muscle strength(Up to 28 weeks)
- Serum neurofilament light(Up to 28 weeks)
- Forced Vital Capacity (FVC)(Up to 28 weeks)
- Lymphocyte Mitochondrial Function(Up to 28 weeks)
- ALS Functional Rating Scale-Revised (ALSFRS-R)(Up to 28 weeks)
研究者
Swathy Chandrashekhar, MBBS
Principal Investigator
University of California, San Francisco