A Phase 1 interventional study of Spironolactone and Prednisolone in Muscular Dystrophy, Duchenne, sponsored by Kevin Flanigan. Terminated at 4 sites in United States. Open to male participants aged 4 Years to 7 Years. Per ClinicalTrials.gov, last updated 2023-10-23.
Sponsored by Kevin Flanigan · Phase 1, Interventional, and Treatment
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).
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.
548 studies on the registry are indexed under Muscular Dystrophies; 89 are open to participants now.
This study's enrollment of 2 is below the median of 24 across 344 interventional studies indexed under Muscular Dystrophies.
Browse Muscular Dystrophies studies →Kevin Flanigan is the lead sponsor of 4 studies on the registry; none are open to participants now.
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Exclusion Criteria:
An anticipated 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
An anticipated 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
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.
Prednisolone will be prescribed for 6 months as the clinical standard of care.
Efficacy: Change in Time to Complete a 100 Meter Timed Test.
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).
Time frame: 6 months
Safety Will be Monitored Through Regular Review of Electrolytes.
Electrolytes (Sodium, Potassium, Cloride and Carbon dioxide, mmol/L) will be measured on a monthly basis following initiation of either spironolactone or prednisolone.
Time frame: 6 months
Efficacy: Dynamometry Score
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
Time frame: 6 months
| Milestone | Spironolactone | Prednisolone |
|---|---|---|
| Started | 1 | 1 |
| Completed | 1 | 1 |
| Not completed | 0 | 0 |
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).
| sec | Spironolactone | Prednisolone |
|---|---|---|
| Efficacy: Change in Time to Complete a 100 Meter Timed Test. | -0.6 | -5.3 |
Electrolytes (Sodium, Potassium, Cloride and Carbon dioxide, mmol/L) will be measured on a monthly basis following initiation of either spironolactone or prednisolone.
| mmol/L | Spironolactone | Prednisolone |
|---|---|---|
| Sodium-Baseline | 142 | 140 |
| Sodium-Month 1 | 142 | 140 |
| Sodium-Month 2 | 141 | 139 |
| Sodium-Month 3 | 142 | 141 |
| Sodium-Month 4 | 139 | 139 |
| Sodium-Month 5 | 139 | 139 |
| Sodium-Month 6 | 140 | 143 |
| Potassium-Baseline | 4.5 | 3.8 |
| Potassium-Month 1 | 4.7 | 4 |
| Potassium-Month 2 | 4.2 | 4.5 |
| Potassium-Month 3 | 4.1 | 3.9 |
| Potassium-Month 4 | 4.5 | 4.6 |
| Potassium-Month 5 | 4.5 | 4.2 |
| Potassium-Month 6 | 4.3 | 3.9 |
| Chloride-Baseline | 103 | 105 |
| Chloride-Month 1 | 109 | 105 |
| Chloride-Month 2 | 107 | 104 |
| Chloride-Month 3 | 103 | 105 |
| Chloride-Month 4 | 103 | 105 |
| Chloride-Month 5 | 103 | 106 |
| Chloride-Month 6 | 101 | 105 |
| CO2-Baseline | 29 | 22 |
| CO2-Month 1 | 22 | 24 |
| CO2-Month 2 | 25 | 24 |
| CO2-Month 3 | 27 | 24 |
| CO2-Month 4 | 28 | 25 |
| CO2-Month 5 | 28 | 26 |
| CO2-Month 6 | 26 | 26 |
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
| kg | Spironolactone | Prednisolone |
|---|---|---|
| Elbow Flexion (Right)-Baseline | 0 | 3.6 |
| Elbow Flexion (Left)-Baseline | 0 | 4.1 |
| Elbow Extension (Right)-Baseline | 0 | 5.3 |
| Elbow Extension (Left)-Baseline | 0 | 4.1 |
| Knee Flexion (Right)-Baseline | 4.1 | 3.3 |
| Knee Flexion (Left)-Baseline | 2.8 | 3.4 |
| Knee Extension (Right)-Baseline | 3.8 | 4.8 |
| Knee Extension (Left)-Baseline | 5.9 | 5.2 |
| Elbow Flexion (Right)-Month 6 | 3.1 | 2.9 |
| Elbow Flexion (Left)-Month 6 | 3.5 | 3.4 |
| Elbow Extension (Right)-Month 6 | 2.4 | 4.3 |
| Elbow Extension (Left)-Month 6 | 2.5 | 3.8 |
| Knee Flexion (Right)-Month 6 | 4.3 | 4.1 |
| Knee Flexion (Left)-Month 6 | 4.1 | 3.9 |
| Knee Extension (Right)-Month 6 | 7.2 | 6 |
| Knee Extension (Left)-Month 6 | 8.3 | 5.1 |
Collected over Data was collected for each participant over a 7 month duration.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Spironolactone | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Prednisolone | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Event | Spironolactone | Prednisolone |
|---|---|---|
| Viral IllnessGastrointestinal disorders | 1/1 | 0/1 |
| Loose StoolGastrointestinal disorders | 1/1 | 0/1 |
| Muscle CrampsMusculoskeletal and connective tissue disorders | 0/1 | 1/1 |
| Dental CavityGastrointestinal disorders | 0/1 | 1/1 |
| Age, Categorical(Participants) | Spironolactone | Prednisolone | Total |
|---|---|---|---|
| <=18 years | 1 | 1 | 2 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Spironolactone | Prednisolone | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 1 | 1 | 2 |
| Ethnicity (NIH/OMB)(Participants) | Spironolactone | Prednisolone | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 1 | 1 | 2 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Spironolactone | Prednisolone | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 1 | 1 | 2 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Spironolactone | Prednisolone | Total |
|---|---|---|---|
| United States | 1 | 1 | 2 |
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Kevin Flanigan