spironolactone and Becker Muscular Dystrophy studies

Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
spironolactone : A steroid lactone that is 17alpha-pregn-4-ene-21,17-carbolactone substituted by an oxo group at position 3 and an alpha-acetylsulfanyl group at position 7.

Research Excerpts

Excerpt	Relevance	Reference
"In boys with Duchenne muscular dystrophy and preserved ejection fraction, addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function."	2.80	Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. ( Cripe, LH; Halnon, NJ; He, X; Hor, KN; Jefferies, JL; Kissel, JT; Lowe, J; Mazur, W; McCarthy, B; Rafael-Fortney, JA; Raman, SV; Roble, SL; Smart, S; Taylor, MD; Tran, T, 2015)
"Eplerenone treatment alone decreased a number of important muscle-specific genes."	1.46	Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle. ( Chadwick, JA; Gomez-Sanchez, CE; Gomez-Sanchez, EP; Hauck, JS; Rafael-Fortney, JA, 2017)
"As life expectancy of patients with Duchenne muscular dystrophy (DMD) has increased to the 5th decade, in part due to improved ventilatory support, cardiomyopathy is projected to increase as a cause of death."	1.40	Cardiac management of ventilator-assisted individuals with Duchenne muscular dystrophy. ( Evans, RA; Goldstein, RS; O'Brien, L; Varadi, R, 2014)
"Severe muscle fibrosis is the endpoint of many chronic myopathies."	1.39	Duchenne muscular dystrophy fibroblast nodules: a cell-based assay for screening anti-fibrotic agents. ( Gibertini, S; Mantegazza, R; Mora, M; Savadori, P; Zanotti, S, 2013)
"Nearly universal cardiomyopathy in Duchenne muscular dystrophy (DMD) contributes to heart failure and death."	1.37	Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in Duchenne muscular dystrophy mice. ( Canan, BD; Chimanji, NS; Delfín, DA; Ganguly, R; Janssen, PM; Martin, CD; Mays, TA; Murray, JD; Rafael-Fortney, JA; Raman, SV; Schill, KE; Stangland, JE; Tran, T; Xu, Y, 2011)

Research

Studies (18)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Left Ventricular Strain

Efficacy: Change in Time to Complete a 100 Meter Timed Test.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (5.56)	29.6817
2010's	15 (83.33)	24.3611
2020's	2 (11.11)	2.80

Authors	Studies
Howard, ZM	1
Gomatam, CK	1
Rabolli, CP	1
Lowe, J	3
Piepho, AB	1
Bansal, SS	1
Accornero, F	2
Rafael-Fortney, JA	6
Raman, SV	5
Hor, KN	3
Mazur, W	3
Cardona, A	1
He, X	3
Halnon, N	1
Markham, L	1
Soslow, JH	1
Puchalski, MD	1
Auerbach, SR	1
Truong, U	1
Smart, S	3
McCarthy, B	3
Saeed, IM	1
Statland, JM	1
Kissel, JT	3
Cripe, LH	3
Birnkrant, DJ	1
Black, JB	1
Breitenbach, S	2
Lehmann-Horn, F	4
Jurkat-Rott, K	4
Chadwick, JA	1
Hauck, JS	2
Gomez-Sanchez, CE	1
Gomez-Sanchez, EP	1
Glemser, PA	1
Jaeger, H	1
Nagel, AM	3
Ziegler, AE	1
Simons, D	1
Schlemmer, HP	1
Weber, MA	3
Rastogi, N	2
McElhanon, KE	1
Petrosino, JM	1
Peczkowski, KK	1
Chadwick, AN	1
Zins, JG	1
Janssen, PML	1
Weisleder, NL	1
Zanotti, S	1
Gibertini, S	1
Savadori, P	1
Mantegazza, R	1
Mora, M	1
Janssen, PM	2
Murray, JD	2
Schill, KE	2
Schultz, EJ	1
Tran, T	3
O'Brien, L	1
Varadi, R	1
Goldstein, RS	1
Evans, RA	1
Angelini, C	1
Halnon, NJ	1
Taylor, MD	1
Jefferies, JL	1
Roble, SL	2
Barison, A	1
Aquaro, GD	1
Passino, C	1
Falorni, M	1
Balbarini, A	1
Lombardi, M	1
Pasquali, L	1
Emdin, M	1
Siciliano, G	1
Chimanji, NS	1
Martin, CD	1
Ganguly, R	1
Stangland, JE	1
Xu, Y	1
Canan, BD	1
Mays, TA	1
Delfín, DA	1
Fayssoil, A	1
Wolf, MB	1
Kauczor, HU	1
Semmler, W	1
Meinck, HM	1
Scharrer, J	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy[NCT02354352]	Phase 3	52 participants (Actual)	Interventional	2015-03-20	Completed
Effects of Myofascial Trigger Points Therapy in Migraine.[NCT05646160]		100 participants (Anticipated)	Interventional	2018-01-15	Recruiting
A Randomized Open Label Trial of Spironolactone Versus Prednisolone in Corticosteroid-naïve Boys With DMD[NCT03777319]	Phase 1	2 participants (Actual)	Interventional	2018-12-05	Terminated (stopped due to Inability to recruit participants.)
A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)[NCT03439670]	Phase 2	121 participants (Actual)	Interventional	2018-06-29	Completed
Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy[NCT01521546]		42 participants (Actual)	Interventional	2012-02-29	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	Percent change in circumference (Median)
Eplerenone	0.2
Spironolactone	0.4

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). (NCT03777319)
Timeframe: 6 months

Efficacy: Dynamometry Score

Intervention	sec (Number)
Spironolactone	-0.6
Prednisolone	-5.3

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 (NCT03777319)
Timeframe: 6 months

Safety Will be Monitored Through Regular Review of Electrolytes.

Intervention	kg (Number)
	Elbow Flexion (Right)-Baseline	Elbow Flexion (Left)-Baseline	Elbow Extension (Right)-Baseline	Elbow Extension (Left)-Baseline	Knee Flexion (Right)-Baseline	Knee Flexion (Left)-Baseline	Knee Extension (Right)-Baseline	Knee Extension (Left)-Baseline	Elbow Flexion (Right)-Month 6	Elbow Flexion (Left)-Month 6	Elbow Extension (Right)-Month 6	Elbow Extension (Left)-Month 6	Knee Flexion (Right)-Month 6	Knee Flexion (Left)-Month 6	Knee Extension (Right)-Month 6	Knee Extension (Left)-Month 6
Prednisolone	3.6	4.1	5.3	4.1	3.3	3.4	4.8	5.2	2.9	3.4	4.3	3.8	4.1	3.9	6	5.1
Spironolactone	0	0	0	0	4.1	2.8	3.8	5.9	3.1	3.5	2.4	2.5	4.3	4.1	7.2	8.3

Electrolytes (Sodium, Potassium, Cloride and Carbon dioxide, mmol/L) will be measured on a monthly basis following initiation of either spironolactone or prednisolone. (NCT03777319)
Timeframe: 6 months

Efficacy Measured by Time to Stand Test (TTSTAND) Velocity in Rises/Second Change From Baseline

Intervention	mmol/L (Number)
	Sodium-Baseline	Sodium-Month 1	Sodium-Month 2	Sodium-Month 3	Sodium-Month 4	Sodium-Month 5	Sodium-Month 6	Potassium-Baseline	Potassium-Month 1	Potassium-Month 2	Potassium-Month 3	Potassium-Month 4	Potassium-Month 5	Potassium-Month 6	Chloride-Baseline	Chloride-Month 1	Chloride-Month 2	Chloride-Month 3	Chloride-Month 4	Chloride-Month 5	Chloride-Month 6	CO2-Baseline	CO2-Month 1	CO2-Month 2	CO2-Month 3	CO2-Month 4	CO2-Month 5	CO2-Month 6
Prednisolone	140	140	139	141	139	139	143	3.8	4	4.5	3.9	4.6	4.2	3.9	105	105	104	105	105	106	105	22	24	24	24	25	26	26
Spironolactone	142	142	141	142	139	139	140	4.5	4.7	4.2	4.1	4.5	4.5	4.3	103	109	107	103	103	103	101	29	22	25	27	28	28	26

Vamorolone at 6.0mg/kg/day vs. placebo group in change from baseline to the Week 24 assessment (NCT03439670)
Timeframe: 24 weeks

12-month Change in Myocardial Strain

Intervention	Rises/Seconds (Mean)
Treatment Group 1	-.007
Treatment Group 2	0.054

a sensitive measurement of heart function using cardiac MRI, change was 12 months minus baseline. (NCT01521546)
Timeframe: baseline and 12 months

Article	Year
Stabilization of Early Duchenne Cardiomyopathy With Aldosterone Inhibition: Results of the Multicenter AIDMD Trial. Journal of the American Heart Association, 2019, Volume: 8, Issue:19 Topics: Adolescent; Cardiomyopathies; Child; Double-Blind Method; Eplerenone; Humans; Magnetic Resonance Ima	2019
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. The Lancet. Neurology, 2015, Volume: 14, Issue:2 Topics: Adolescent; Cardiomyopathies; Child; Cohort Studies; Double-Blind Method; Early Diagnosis; Eplerenon	2015
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. The Lancet. Neurology, 2015, Volume: 14, Issue:2 Topics: Adolescent; Cardiomyopathies; Child; Cohort Studies; Double-Blind Method; Early Diagnosis; Eplerenon	2015
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. The Lancet. Neurology, 2015, Volume: 14, Issue:2 Topics: Adolescent; Cardiomyopathies; Child; Cohort Studies; Double-Blind Method; Early Diagnosis; Eplerenon	2015
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. The Lancet. Neurology, 2015, Volume: 14, Issue:2 Topics: Adolescent; Cardiomyopathies; Child; Cohort Studies; Double-Blind Method; Early Diagnosis; Eplerenon	2015
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial. Orphanet journal of rare diseases, 2017, 02-20, Volume: 12, Issue:1 Topics: Adolescent; Adult; Cardiomyopathies; Child; Double-Blind Method; Eplerenone; Humans; Male; Mineraloc	2017

Article	Year
Mineralocorticoid receptor antagonists and glucocorticoids differentially affect skeletal muscle inflammation and pathology in muscular dystrophy. JCI insight, 2022, 10-10, Volume: 7, Issue:19 Topics: Animals; Cytokines; Fibronectins; Glucocorticoids; Inflammation; Mice; Mice, Inbred mdx; Mineralocor	2022
Eplerenone repolarizes muscle membrane through Na,K-ATPase activation by Tyr10 dephosphorylation. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology, 2016, Volume: 35, Issue:2 Topics: Animals; Cell Line; Diaphragm; Enzyme Inhibitors; Eplerenone; Membrane Potentials; Mice; Mineralocor	2016
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle. Physiological genomics, 2017, Jun-01, Volume: 49, Issue:6 Topics: Adolescent; Adult; Aldosterone; Blotting, Western; Cells, Cultured; Eplerenone; Humans; Male; Muscle	2017
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology, 2017, Volume: 36, Issue:1 Topics: Adipose Tissue; Child; Diuretics; Edema; Elasticity; Eplerenone; Glucocorticoids; Humans; Hydrogen;	2017
Mineralocorticoid receptor antagonists improve membrane integrity independent of muscle force in muscular dystrophy. Human molecular genetics, 2019, 06-15, Volume: 28, Issue:12 Topics: Animals; Cell Membrane; Disease Models, Animal; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Mineralo	2019
Duchenne muscular dystrophy fibroblast nodules: a cell-based assay for screening anti-fibrotic agents. Cell and tissue research, 2013, Volume: 352, Issue:3 Topics: Biological Assay; Blotting, Western; Collagen; Decorin; Drug Evaluation, Preclinical; Enzyme-Linked	2013
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, Volume: 9, Issue:2 Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Diuretics; Dystrophin; Female; Gene Expression;	2014
Cardiac management of ventilator-assisted individuals with Duchenne muscular dystrophy. Chronic respiratory disease, 2014, Volume: 11, Issue:2 Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Diur	2014
Prevention of cardiomyopathy in Duchenne muscular dystrophy. The Lancet. Neurology, 2015, Volume: 14, Issue:2 Topics: Cardiomyopathies; Eplerenone; Humans; Male; Mineralocorticoid Receptor Antagonists; Muscular Dystrop	2015
Cardiac magnetic resonance imaging and management of dilated cardiomyopathy in a Duchenne muscular dystrophy manifesting carrier. Journal of neurology, 2009, Volume: 256, Issue:2 Topics: Adult; Biomarkers; Carbazoles; Cardiomyopathy, Dilated; Carvedilol; Child; Creatine Kinase; Disease	2009
Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in Duchenne muscular dystrophy mice. Circulation, 2011, Aug-02, Volume: 124, Issue:5 Topics: Animals; Cardiac Imaging Techniques; Cardiomyopathies; Cardiotonic Agents; Disease Models, Animal; D	2011
Letter by Fayssoil regarding article, "Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in Duchenne muscular dystrophy mice". Circulation, 2012, Mar-06, Volume: 125, Issue:9 Topics: Animals; Lisinopril; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Myocardium; Spironolactone	2012
Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration. Journal of neurology, 2012, Volume: 259, Issue:11 Topics: Adolescent; Child; Disease Progression; Edema; Eplerenone; Female; Follow-Up Studies; Humans; Male;	2012
Rationale for treating oedema in Duchenne muscular dystrophy with eplerenone. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology, 2012, Volume: 31, Issue:1 Topics: Adult; Animals; Diaphragm; Edema; Eplerenone; Female; Forearm; Humans; In Vitro Techniques; Leg; Mag	2012

spironolactone and Becker Muscular Dystrophy