Safety and Efficacy of Ranolazine for the Treatment of Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
The purpose of this research study is to evaluate the safety and effectiveness of Ranolazine, and how well it is tolerated in patients with Amyotrophic Lateral Sclerosis (ALS). Ranolazine is an FDA approved drug that is used for decreasing chest pain.
详细描述
Amyotrophic Lateral Sclerosis (ALS) is a progressive debilitating and fatal neurodegenerative disease involving the motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord with 5,000 newly diagnosed patients per year in the USA. There is a pressing need for additional therapies, as the only two FDA-approved drugs for ALS, riluzole and edaravone, showed prolongation of median survival of only two to three months and only a modest benefit in daily functioning, respectively. The ability to identify FDA approved drugs which can be repurposed to ALS, and which may slow disease progression, alleviate symptoms, or prolong survival will have an immediate positive impact of the lives of patients with ALS and their family members. Hypothesis: Ranolazine, an FDA approved drug for angina which inhibits the late Na+ current and intracellular Ca2+ accumulation may be neuroprotective in ALS by reducing neuronal hyperexcitability, may slow disease progression and reduce cramp frequency.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients with clinically definite, probable, laboratory supported probable, or possible ALS per revised El Escorial criteria
- •Cramp frequency greater than 4 cramps per week during 2 week run in
- •ALS functional rating scale-revised (ALSFRS-R) score of greater than 24
- •Able to lie on back for study procedures
排除标准
- •Tracheostomy invasive ventilation, or use of non-invasive ventilation greater than 12 hours per day
- •Pregnant or lactating
- •Participation in a prior experimental drug trial less than 30 days prior to screening
- •Patients taking ranolazine
- •Patients taking medications which are contraindicated for use with ranolazine such as strong CYP3 inhibitors (ketoconazole, clarithromycin, nelfinavir), and CYP3 inducers (rifampin, phenobarbital)
- •Patients with clinically significant medical comorbidities (hepatic, renal, cardiac, etc)
- •Patients with baseline QT interval prolongation on Electrocardiography (ECG)
- •Patients pre-disposed to secondary QT prolongation for other health conditions like family history of congenital long QT syndrome, heart failure, bradycardia, or cardiomyopathies
研究组 & 干预措施
Ranolazine 500mg
Participants will take Ranolazine 500mg twice daily for up to 4 weeks.
干预措施: Ranolazine 500 MG (Drug)
Ranolazine 1000mg
Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.
干预措施: Ranolazine 1000 MG (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: Up to Week 12
Measured as any drug-related serious adverse event, or drug-related adverse event necessitating study withdrawal. If a dose has less than 33% DLTs it will be considered tolerable.
次要结局
- Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline(Weekly for 12 weeks)
- Percent Change in Cramp Frequency(Weekly for 12 weeks)
- Percentage Change in Average Weekly Cramp Severity(Weekly for 12 weeks)
- Muscle Fasciculations Count(Up to week 12)
研究者
Jeffrey Statland
Assistant Professor
University of Kansas Medical Center