welcome to DuchenneXchange- a positively charged Duchenne muscular dystrophy community.
- join today!
Spironolactone Versus Prednisolone in DMD
study id #: NCT03777319
condition: Muscular Dystrophy, Duchenne
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).
intervention: Spironolactone, Prednisolone
mechanism of action: Aldosterone-blocking diuretic to delay decline in muscle strength and prevent cardiovascular strain
last updated: December 04, 2019
start date: December 5, 2018
estimated completion: December 2021
phase of development: Phase 1
size / enrollment: 24
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.
- Efficacy: Change in time to complete a 100 meter timed test. [ Time Frame: 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. [ Time Frame: 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.
- Efficacy: Dynamometry score [ Time Frame: 6 months ]
Secondary outcome measures will be Dynamometry score, which is a summation of maximum voluntary isometric contraction test values for knee flexion, knee extension, elbow flexion, and elbow extension; 4-stair climb; North Star Ambulatory Assessment (NSAA); and time to arise from the floor.
• 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 OR a muscle biopsy that demonstrates <5% dystrophin in the patient or an affected relative
• Normal left ventricular ejection fraction by screening echocardiogram
• Ability to cooperate for testing
• No prior glucocorticoid treatment
• No concomitant experimental therapies
• Subject amenable to or currently being treated with eteplirsen
• 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
Longitudinal Pulmonary Function Testing Outcome Measures in Duchenne Muscular Dystrophy: Long-term Natural History w...We describe changes in pulmonary functio...
Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular DystrophyThe study is to demonstrate non-inferior...
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled t...Background: Cardiomyopathy is a leading...
Historically Controlled Trial of Corticosteroids in Young Boys With Duchenne Muscular DystrophyWhile it has been known for many years t...
Eplerenone for Subclinical Cardiomyopathy in Duchenne Muscular DystrophyDuchenne muscular dystrophy (DMD), the m...
Growth Hormone Increases Bone Toughness and Decreases Muscle Inflammation in Glucocorticoid-Treated Mdx Mice, Model ...The absence of functional dystrophin wit...
CureDuchenne Invests in ZappRx Platform to Streamline Specialty Prescribing for Patients Suffering from Duchenne Mus...ZappRx, Inc., a digital health company t...
Developing standardized corticosteroid treatment for Duchenne muscular dystrophyDespite corticosteroids being the only t...