A Randomized Open Label Trial of Spironolactone Versus Prednisolone in Corticosteroid-naïve Boys With DMD
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 4
- 主要终点
- Efficacy: Change in Time to Complete a 100 Meter Timed Test.
研究概览
简要总结
This is a randomized, open-label, pilot clinical trial of spironolactone suspension versus oral prednisolone for use in Duchenne muscular dystrophy. The goals are to determine the safety of 6 months of treatment with spironolactone treatment int he steroid-naive DMD population as well as to determine if either spironolactone or a standard clinical dose of corticosteroids results in equivalent improvement in time to complete the 100 meter timed test (100M).
详细描述
Until recently, the only treatment shown to improve strength and preserve ambulation in DMD patients was the use of glucocorticoids, which are accompanied by significant side effects including obesity, cushingoid features, osteoporosis, and behavioral disturbances. Spironolactone is an aldosterone antagonist primarily used as a potassium sparing diuretic that is widely used in the pediatric population, with limited side-effects including gynecomastia and hyperkalemia. Recent studies by Dr. Rafael-Fortney have evaluated the effect of spironolactone treatment in several different mouse models of DMD. Her results show that treatment of these mice demonstrates increased muscle membrane stabilization while reducing the negative side-effects typically associated with standard of care glucocorticoids. This pilot study is designed to determine whether this commonly used medication, spironolactone, may have similar beneficial effects with a lower side effect profile and be applicable to a wider population of DMD patients.
The hypothesis for this controlled pilot trial is that spironolactone and prednisolone are of equal efficacy in improving skeletal muscle function over a 6-month period, and that spironolactone will be well tolerated in this patient population.
One outcome is that both drugs demonstrate equal efficacy in motor function. This would then serve as pilot data for a longer term study.
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
- None
入排标准
- 年龄范围
- 4 Years 至 7 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Duchenne muscular dystrophy (DMD) patients ≥4 to ≤7 years of age
- •Clinical features of DMD that include proximal predominant weakness and/or gait disturbance
- •Presence of a truncating mutation of the DMD gene in the patient or an affected male relative OR a muscle biopsy that demonstrates <5% dystrophin in the patient or an affected male relative
- •Normal left ventricular ejection fraction by screening echocardiogram
- •Ability to cooperate for testing
- •No prior treatment with glucocorticoids or vamorolone
- •No concomitant experimental therapies
排除标准
- •Subject amenable to or currently being treated with eteplirsen, casimersen, or viltolarsen
- •Hyperkalemia at screening
- •History of or ongoing renal failure (elevated creatinine, oliguria, anuria)
- •Hypersensitivity to spironolactone (rash, respiratory distress, arrhythmia, numbness or tingling of extremities)
- •Current treatment with an ACEi
- •Severe peptic ulcer disease or recent gastrointestinal perforations
研究组 & 干预措施
Spironolactone
An anticipated twelve subjects will be prescribed a standard clinical dose of spironolactone of 1 mg/kg/day. The spironolactone will be provided as suspension.
干预措施: Spironolactone (Drug)
Prednisolone
An anticipated twelve subjects will be prescribed a standard clinical dose of prednisolone of 0.75 mg/kg/day or weekend dosing per sites standard of care. The prednisolone will be provided will be provided as suspension.
干预措施: Prednisolone (Drug)
结局指标
主要结局
Efficacy: Change in Time to Complete a 100 Meter Timed Test.
时间窗: 6 months
The determination of whether spironolactone has similar efficacy to glucocorticoids in improving muscle strength in steroid naïve DMD patients. This will be determined by measuring the time to complete a 100 meter timed test (100M).
Safety Will be Monitored Through Regular Review of Electrolytes.
时间窗: 6 months
Electrolytes (Sodium, Potassium, Cloride and Carbon dioxide, mmol/L) will be measured on a monthly basis following initiation of either spironolactone or prednisolone.
次要结局
- Efficacy: Dynamometry Score(6 months)
研究者
Kevin Flanigan
Professor of Neurology
Nationwide Children's Hospital