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Spironolactone Versus Prednisolone in DMD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03777319
Recruitment Status : Terminated (Inability to recruit participants.)
First Posted : December 17, 2018
Last Update Posted : January 20, 2022
Muscular Dystrophy Association
Information provided by (Responsible Party):
Kevin Flanigan, Nationwide Children's Hospital

Brief 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).

Condition or disease Intervention/treatment Phase
Muscular Dystrophy, Duchenne Drug: Spironolactone Drug: Prednisolone Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomly assigned to either to the spironolactone treatment group or to the standard clinical dose of corticosteroids.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Open Label Trial of Spironolactone Versus Prednisolone in Corticosteroid-naïve Boys With DMD
Actual Study Start Date : December 5, 2018
Actual Primary Completion Date : September 27, 2021
Actual Study Completion Date : November 30, 2021

Arm Intervention/treatment
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 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.

Primary Outcome Measures :
  1. 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).

  2. 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.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 7 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03777319

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United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
Kevin Flanigan
Muscular Dystrophy Association
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Principal Investigator: Kevin Flanigan, MD Nationwide Children's Hospital
Principal Investigator: Megan Waldrop, MD Nationwide Children's Hospital

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Responsible Party: Kevin Flanigan, Professor of Neurology, Nationwide Children's Hospital Identifier: NCT03777319    
Other Study ID Numbers: IRB17-00240
First Posted: December 17, 2018    Key Record Dates
Last Update Posted: January 20, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Diuretics, Potassium Sparing
Natriuretic Agents