Spironolactone Versus Prednisolone in DMD

Summary

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).

Timeline

Start

2018-12-05

Primary completion

2021-09-27

Completion

2021-11-30

Publications

• Background Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003725. doi: 10.1002/14651858.CD003725.pub3.
• Background Buck ML. Clinical experience with spironolactone in pediatrics. Ann Pharmacother. 2005 May;39(5):823-8. doi: 10.1345/aph.1E618. Epub 2005 Apr 5.
• Background Rafael-Fortney JA, Chimanji NS, Schill KE, Martin CD, Murray JD, Ganguly R, Stangland JE, Tran T, Xu Y, Canan BD, Mays TA, Delfin DA, Janssen PM, Raman SV. Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in Duchenne muscular dystrophy mice. Circulation. 2011 Aug 2;124(5):582-8. doi: 10.1161/CIRCULATIONAHA.111.031716. Epub 2011 Jul 18.
• Background Janssen PM, Murray JD, Schill KE, Rastogi N, Schultz EJ, Tran T, Raman SV, Rafael-Fortney JA. Prednisolone attenuates improvement of cardiac and skeletal contractile function and histopathology by lisinopril and spironolactone in the mdx mouse model of Duchenne muscular dystrophy. PLoS One. 2014 Feb 13;9(2):e88360. doi: 10.1371/journal.pone.0088360. eCollection 2014.
• Background Lowe J, Floyd KT, Rastogi N, Schultz EJ, Chadwick JA, Swager SA, Zins JG, Kadakia FK, Smart S, Gomez-Sanchez EP, Gomez-Sanchez CE, Raman SV, Janssen PM, Rafael-Fortney JA. Similar efficacy from specific and non-specific mineralocorticoid receptor antagonist treatment of muscular dystrophy mice. J Neuromuscul Dis. 2016;3(3):395-404. doi: 10.3233/JND-160173.
• Background Chadwick JA, Hauck JS, Lowe J, Shaw JJ, Guttridge DC, Gomez-Sanchez CE, Gomez-Sanchez EP, Rafael-Fortney JA. Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target. FASEB J. 2015 Nov;29(11):4544-54. doi: 10.1096/fj.15-276782. Epub 2015 Jul 15.
• Background Chadwick JA, Swager SA, Lowe J, Welc SS, Tidball JG, Gomez-Sanchez CE, Gomez-Sanchez EP, Rafael-Fortney JA. Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy. Hum Mol Genet. 2016 Dec 1;25(23):5167-5177. doi: 10.1093/hmg/ddw331.
• Background Alfano LN, Miller NF, Berry KM, Yin H, Rolf KE, Flanigan KM, Mendell JR, Lowes LP. The 100-meter timed test: Normative data in healthy males and comparative pilot outcome data for use in Duchenne muscular dystrophy clinical trials. Neuromuscul Disord. 2017 May;27(5):452-457. doi: 10.1016/j.nmd.2017.02.007. Epub 2017 Feb 17.

Drugs

Indications