Becker Muscular Dystrophy Clinical Trial
— WSiMDOfficial title:
Open Label Safety and Efficacy of Once Weekly Steroid in Patients With LGMD and Becker Muscular Dystrophy
Verified date | September 2023 |
Source | Northwestern University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to evaluate the safety and efficacy of oral weekly glucocorticoid steroids in patients with Becker Muscular Dystrophy (BMD), an inherited disorder in which patients experience weakness of the legs and pelvis, and Limb Girdle Muscular Dystrophy (LGMD), an inherited disorder in which patients experience progressive muscular weakness predominately in their hip and shoulders. The primary objective is safety which we the investigators will measure using laboratory testing and forced vital capacity (FVC), a breathing test that measures the strength of your lungs. The secondary objective is efficacy which will be measured by a change in MRI muscle mass, improved muscle performance, and quality of life. The investigators hypothesize that patients who receive oral weekly glucocorticoid steroids will have improviements in strength and quality of life compared to their baseline. Furthermore, the investigators anticipate that oral weekly glucocorticoid steroids will not have significant adverse impact on patients.
Status | Completed |
Enrollment | 20 |
Est. completion date | March 1, 2022 |
Est. primary completion date | June 1, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: 1. Patients with Becker muscular dystrophy or LGMD2A (CAPN3), LGMD 2B (DYSF), LGMD 2C (SGCG), LGMD2E (SGCB), LGMD2F (SGCD), LGMD 2I (FKRP), LGMD (ANO5). Genetic mutation or muscle biopsy staining required to confirm genetic subtype 2. Ages 18-65 years 3. EKG without evidence of prior infarct or atrial fibrillation done within 2 months of study initiation. 4. Echocardiogram with LVEF >25% done within 6 months of study initiation. 5. Stable medications (same medication and dose) for the previous 3 months 6. Stable pulmonary status for the previous 6 months (No change in FVC by more than 20% in the past 6-months) Exclusion Criteria: 1. Diabetes 2. BMI>35 kg/m2 3. Cardiac transplantation 4. Myocardia Infarct in the past 2-years from screening 5. Any history of tuberculosis 6. Untreated or uncontrolled (medication and/or dose change in previous month from screening) hypertension 7. A diagnosis of congestive heart failure 8. A diagnosis of chronic kidney disease 9. A diagnosis of untreated hypothyroidism 10. The patient is believed to be at high risk of osteoporosis by the primary investigator 11. Inability to provide consent 12. Full time ventilator dependency 13. Heart failure symptoms or LVEF <25% 14. Orthopedic surgery within the prior year or upcoming elective orthopedic surgery within the 6-months from Day 0. 15. Inability to complete MRI (claustrophobia, metal implants) 16. Pregnant women at screening, women seeking to become pregnant, or men seeking to father a child within 6-months from Day 0 should not participate in this study. |
Country | Name | City | State |
---|---|---|---|
United States | Northwestern University | Chicago | Illinois |
Lead Sponsor | Collaborator |
---|---|
Northwestern University |
United States,
Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, Case LE, Clemens PR, Hadjiyannakis S, Pandya S, Street N, Tomezsko J, Wagner KR, Ward LM, Weber DR; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018 Mar;17(3):251-267. doi: 10.1016/S1474-4422(18)30024-3. Epub 2018 Feb 3. Erratum In: Lancet Neurol. 2018 Apr 4;: — View Citation
Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kornberg AJ, Bertorini TE, Nevo Y, Lotze T, Pestronk A, Ryan MM, Monasterio E, Day JW, Zimmerman A, Arrieta A, Henricson E, Mayhew J, Florence J, Hu F, Connolly AM. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011 Aug 2;77(5):444-52. doi: 10.1212/WNL.0b013e318227b164. Epub 2011 Jul 13. — View Citation
Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 Feb 2;86(5):465-72. doi: 10.1212/WNL.0000000000002337. — View Citation
Quattrocelli M, Barefield DY, Warner JL, Vo AH, Hadhazy M, Earley JU, Demonbreun AR, McNally EM. Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy. J Clin Invest. 2017 Jun 1;127(6):2418-2432. doi: 10.1172/JCI91445. Epub 2017 May 8. — View Citation
Quattrocelli M, Salamone IM, Page PG, Warner JL, Demonbreun AR, McNally EM. Intermittent Glucocorticoid Dosing Improves Muscle Repair and Function in Mice with Limb-Girdle Muscular Dystrophy. Am J Pathol. 2017 Nov;187(11):2520-2535. doi: 10.1016/j.ajpath.2017.07.017. Epub 2017 Aug 18. Erratum In: Am J Pathol. 2021 Nov;191(11):2039. — View Citation
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Fasting Glucose | mg/dL, 0-unlimited, higher score indicates worse outcome | Baseline and 6 months (Final Visit) | |
Primary | HbgA1c | % , 0-100, higher score indicates worse outcome | Baseline and 6 months (Final Visit) | |
Primary | Fasting Lipid Profile | cholesterol levels - mg/dL, higher levels indicate worse outcomes | Baseline and 6 months (Final Visit) | |
Primary | Creatine Kinase | units/L, 0-unlimited, higher scores indicate worse outcome | Baseline and 6 months (Final Visit) | |
Primary | Respiratory Changes | Force Vital Capacity (% of predicted value), decrease in FVC indicates declining respiratory function. | Baseline, 6 months | |
Secondary | Functional Assessments - NSAD Change | Northstar Assessment for Dysferlinopathy
- score out of 58, range from 0 to 58, higher score indicates greater functional ability. |
Baseline, Month 6 | |
Secondary | 6 Minute Walk Test | number of meters walked in 6 minute period. Higher values indicate more motor function. | Baseline, Month 6 | |
Secondary | 10 Meter Run Timed | time in seconds to walk/run 10 meters , less time to run indicates greater motor function | Baseline, Month 6 | |
Secondary | Brooke Scale Score | upper extremity assessment, scoring between 1- 6, lower score indicates more upper extremity function | Baseline, Month 6 | |
Secondary | Vignos Scale Score | Lower extremity assessment, score from 1-10, lower score indicates more function. | Baseline, Month 6 | |
Secondary | Muscle Imaging | MRI of leg muscles to measure changes in muscle fat percentage. The data point was collected by taking fat percentage at 6 months minus fat percentage at baseline with the following equation: (([final fat percentage - initial fat percentage]/initial fat percentage) * 100%)). All participants were included, both ambulatory and nonambulatory, with all genetic subtypes included. Five participants didn't have an MRI scan at 6 months and therefore were not included. Muscles imaged were analyzed for muscle fat changes from baseline to 6 months. Data is limited in interpretation due to various muscle groups in both ambulatory and non-ambulatory patients. | Baseline, 6 months | |
Secondary | Bone Density | whole dexa body scan to assess bone density with Z scores (more negative z score indicates increased risk for fractures).
Z-score of 0 represents the population mean, and is the average bone density. Positive scores indicate greater bone density and negative scores indicate decreased bone density, which could be clinically correlated with osteoporosis. |
Baseline, 6 months | |
Secondary | Lean Mass % | whole body dexa scans to assess lean mass % (0- 100 %). Increase lean mass % is the desired outcome. | Baseline, 6 months | |
Secondary | Functional Assessments - Upper Limb Strength | Grip strength of the total force (Newtons) in both hands.
Participants attempted 3 trials in the right hand that was then averaged to create a right-hand average force score. Then, the participants attempted 3 trials in the left hand that was then averaged to create a left-hand average force score. The right-hand average force score was added to the left-hand average force score to create a total grip strength score. |
Baseline and 6 months | |
Secondary | Muscle Strength Test | Manual motor testing of the right knee flexion muscle group. | baseline, 6 months |
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