Spironolactone Versus Prednisolone in DMD
Nøgleord
Abstrakt
Beskrivelse
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.
Datoer
| Sidst bekræftet: | 01/31/2020 |
| Først indsendt: | 12/09/2018 |
| Anslået tilmelding indsendt: | 12/12/2018 |
| Først indsendt: | 12/16/2018 |
| Sidste opdatering indsendt: | 02/17/2020 |
| Sidste opdatering indsendt: | 02/19/2020 |
| Faktisk startdato for undersøgelsen: | 12/04/2018 |
| Anslået primær afslutningsdato: | 11/30/2021 |
| Anslået afslutningsdato for undersøgelsen: | 11/30/2021 |
Tilstand eller sygdom
Intervention / behandling
Drug: Spironolactone
Drug: Prednisolone
Fase
Armgrupper
| Arm | Intervention / behandling |
|---|---|
| Experimental: Spironolactone Twelve subjects will be prescribed a standard clinical dose of spironolactone of 1 mg/kg/day. The spironolactone will be provided as suspension. | Drug: Spironolactone Spironolactone will be prescribed for 6 months, after which the family and primary care physician will determine to either remain on spironolactone or transfer to prednisolone. |
| Active Comparator: Prednisolone Twelve subjects will be prescribed a standard clinical dose of prednisolone of 0.75 mg/kg/day or weekend dosing of 5 mg/kg/day as per sites standard of care. The prednisolone will be provided will be provided as suspension. | Drug: Prednisolone Prednisolone will be prescribed for 6 months as the clinical standard of care. |
Kriterier for støtteberettigelse
| Alder berettiget til undersøgelse | 4 Years Til 4 Years |
| Køn, der er berettiget til undersøgelse | Male |
| Accepterer sunde frivillige | Ja |
| Kriterier | Inclusion Criteria: - 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 Exclusion Criteria: - 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 |
Resultat
Primære resultatforanstaltninger
1. Efficacy: Change in time to complete a 100 meter timed test. [6 months]
2. Safety will be monitored through regular review of electrolytes. [6 months]
Sekundære resultatforanstaltninger
1. Efficacy: Dynamometry score [6 months]
