Weekly Steroids in Muscular Dystrophy

NCT04054375 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STU00208443
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Limb-girdle Muscular Dystrophy; Becker Muscular Dystrophy

Keywords

Steroids, Prednisone

Outcome Measures

Primary Outcomes (5)

• Fasting Glucose

  mg/dL, 0-unlimited, higher score indicates worse outcome

  Baseline and 6 months (Final Visit)

• HbgA1c

  % , 0-100, higher score indicates worse outcome

  Baseline and 6 months (Final Visit)

• Fasting Lipid Profile

  cholesterol levels - mg/dL, higher levels indicate worse outcomes

  Baseline and 6 months (Final Visit)

• Creatine Kinase

  units/L, 0-unlimited, higher scores indicate worse outcome

  Baseline and 6 months (Final Visit)

• Respiratory Changes

  Force Vital Capacity (% of predicted value), decrease in FVC indicates declining respiratory function.

  Baseline, 6 months

Secondary Outcomes (10)

• Functional Assessments - NSAD Change

  Baseline, Month 6

• 6 Minute Walk Test

  Baseline, Month 6

• 10 Meter Run Timed

  Baseline, Month 6

• Brooke Scale Score

  Baseline, Month 6

• Vignos Scale Score

  Baseline, Month 6

Study Arms (1)

Weekly Steroid

EXPERIMENTAL

Subjects will be asked to take weekly GC oral prednisone dosed based on weight (1mg/kg for patients who weigh less than or equal to 70 kg and 0.75 mg/kg for patients who weigh more than 70 kg). Subjects will also be instructed to take their weekly prednisone on Mondays after their last meal between 7 and 9 PM

Drug: Prednisone

Interventions

Prednisone DRUG

Subjects will be asked to take weekly GC oral prednisone dosed based on weight (1mg/kg for patients who weigh less than or equal to 70 kg and 0.75 mg/kg for patients who weigh more than 70 kg). Subjects will also be instructed to take their weekly prednisone on Mondays after their last meal between 7 and 9 PM

Also known as: Prednisolone

Weekly Steroid

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Ages 18-65 years
• EKG without evidence of prior infarct or atrial fibrillation done within 2 months of study initiation.
• Echocardiogram with LVEF \>25% done within 6 months of study initiation.
• Stable medications (same medication and dose) for the previous 3 months
• Stable pulmonary status for the previous 6 months (No change in FVC by more than 20% in the past 6-months)

You may not qualify if:

• Diabetes
• BMI\>35 kg/m2
• Cardiac transplantation
• Myocardia Infarct in the past 2-years from screening
• Any history of tuberculosis
• Untreated or uncontrolled (medication and/or dose change in previous month from screening) hypertension
• A diagnosis of congestive heart failure
• A diagnosis of chronic kidney disease
• A diagnosis of untreated hypothyroidism
• The patient is believed to be at high risk of osteoporosis by the primary investigator
• Inability to provide consent
• Full time ventilator dependency
• Heart failure symptoms or LVEF \<25%
• Orthopedic surgery within the prior year or upcoming elective orthopedic surgery within the 6-months from Day 0.
• Inability to complete MRI (claustrophobia, metal implants)

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (6)

• 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.

  PMID: 29395989 BACKGROUND

• 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.

  PMID: 21753160 BACKGROUND

• Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy [RETIRED]: 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.

  PMID: 26833937 BACKGROUND

• 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.

  PMID: 28481224 BACKGROUND

• 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.

  PMID: 28823869 BACKGROUND

• Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Muller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmuller H. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26.

  PMID: 23406536 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Duchenne

Interventions

Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Limitations and Caveats

Some patients were not able to complete the study visits at end of the study due to COVID-19 and fearing safely coming to our site for visits. This is why many metrics do not have 20 data points. All patients completed the 24 weeks of steroid dosing and adverse event check-in. No participants left the study early.

Results Point of Contact

• Title: Dr. Senda Ajroud-Driss
• Organization: Northwestern University School of Medicine

s-ajroud@northwestern.edu

(312) 944-0063

Study Officials

• Senda Ajroud-Driss, MD

  Associate Professor of Neurology (Neuromuscular Disease)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology (Neuromuscular Disease)

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 13, 2019
• Study Start: July 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: March 1, 2022
• Last Updated: September 21, 2023
• Results First Posted: July 8, 2021

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)