Spironolactone Versus Prednisolone in DMD
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| ClinicalTrials.gov Identifier: NCT03777319 |
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Recruitment Status :
Terminated
(Inability to recruit participants.)
First Posted : December 17, 2018
Last Update Posted : January 20, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Muscular Dystrophy, Duchenne | Drug: Spironolactone Drug: Prednisolone | Phase 1 |
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.
| 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 |
|---|---|
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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.
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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. |
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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.
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Drug: Prednisolone
Prednisolone will be prescribed for 6 months as the clinical standard of care. |
- 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.
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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
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 ClinicalTrials.gov identifier (NCT number): NCT03777319
| 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 | |
| Principal Investigator: | Kevin Flanigan, MD | Nationwide Children's Hospital | |
| Principal Investigator: | Megan Waldrop, MD | Nationwide Children's Hospital |
| Responsible Party: | Kevin Flanigan, Professor of Neurology, Nationwide Children's Hospital |
| ClinicalTrials.gov 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 |
| 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 |
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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 Prednisolone Spironolactone Anti-Inflammatory Agents |
Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Mineralocorticoid Receptor Antagonists Hormone Antagonists Diuretics, Potassium Sparing Diuretics Natriuretic Agents |