A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor:
Collaborator:
Children's Research Institute
Information provided by (Responsible Party):
Nancy Kuntz, MD, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier:
NCT02036463
First received: January 6, 2014
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease for which no curative treatment has yet been identified, making it important to slow progression and improve the quality of life among affected boys and young men. Treatment with corticosteroids is standard of care for patients with DMD five years old and older, due to the robust observation that this intervention lengthens the interval prior to loss of ambulation but is associated with many side effects. This clinical trial will be conducted in the youngest age group able to receive corticosteroids orally and on whom study outcomes are measurable, ages 3 to 7 years. This is a randomized, double blinded, double masked, placebo-controlled clinical trial that will explore whether better synchronization of corticosteroid administration with the circadian rhythm will provide improved tolerability and at least comparable efficacy to current standards in which corticosteroids are always given in the morning. Furthermore, the trial provides a unique opportunity to rigorously evaluate corticosteroid effects in the young DMD patient, both for efficacy as compared to placebo and as a study of the impact of corticosteroid chronotherapy, or delayed release, on increased tolerability over standard therapy. The main hypothesis is that synchronization of the timing of corticosteroid dosing will improve medication tolerability in children, while maintaining (non-inferiority) the efficacy of corticosteroid. The study also offers a unique opportunity to measure several biomarkers as well as novel genetic modifiers that may further impact the response to corticosteroid in DMD.


Condition Intervention Phase
Duchenne Muscular Dystrophy (DMD)
Drug: Prednisone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: CINRG0513: A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Ann & Robert H Lurie Children's Hospital of Chicago:

Primary Outcome Measures:
  • Safety [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    The primary outcome will measure safety and tolerability by tabulating number of adverse events occuring in patients in each treatment group. Adverse events are specified in the protocol and relate to excess weight gain, inadequate linear growth, elevated blood pressure, worsening scores on behavior scales, declining heart rate variability and abnormalities of circadian rhythm of sympathetic tone.


Secondary Outcome Measures:
  • Time to walk/run 50 meters [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    This test will measure the time it will take to run/walk 50 meters. It has not been typically used in clinical trials as a timed test measure, however, may be a more sensitive test measure in the very young cohort to assess functional strength as it measures a longer distance to run compared to the 10 meter walk. Preliminary analysis in a small pilot cohort indicates that it is better correlated with other functional assessments such as the North Star Ambulatory Assessment.

  • North Star Ambulatory Assessment (NSAA) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The NSAA is a clinician rated 17-item functional scale originally designed for ambulant boys with DMD who are able to ambulate at least 10 meters. This evaluation tool assesses functional activities including standing, getting up from the floor, negotiating steps, hopping, and running. The assessment is based on a 3-point rating scale of 2= ability to perform the test normally, 1= modified method or assistance to perform test, 0=unable to perform the test. Thus, total score can range from 0 (completely non-ambulant) to 34 (no impairment) on these assessments. NSAA has shown good reliability and validity in multi-center studies as well as good clinical validity demonstrated with Rasch analysis.


Estimated Enrollment: 60
Study Start Date: November 2014
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Immediate Release Prednisone
During the entire 18 months of the protocol, these subjects will receive immediate release prednisone as a morning dose. All observations and measurements are performed the same as the other study groups.
Drug: Prednisone
Experimental: Delayed Release Prednisone
During the entire 18 months of the protocol, these subjects will receive delayed release prednisone as an evening dose. All observations and measurements are performed the same as the other study groups.
Drug: Prednisone
Placebo Comparator: Placebo-Delayed Release Prednisone
During the first 6 months of the protocol, these subjects will receive placebo. After 6 months, this half of the placebo group was re-randomized to receive the delayed release prednisone medication. All observations and measurements are performed the same as the other study groups.
Drug: Prednisone Drug: Placebo
Placebo Comparator: Placebo-Immediate Release Prednisone
During the first 6 months of the protocol, these subjects will receive placebo. After 6 months, this half of the placebo group was re-randomized to receive the immediate release corticosteroid medication. All observations and measurements are performed the same as the other study groups.
Drug: Prednisone Drug: Placebo

  Eligibility

Ages Eligible for Study:   3 Years to 6 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Genetically confirmed dystrophin mutation compatible with DMD phenotype. Specifically, gene deletion test positive (missing one or more exons) in the central rod domain (exons 25-60) of dystrophin, where reading frame can be predicted as 'out-of-frame' OR showing complete absence of dystrophin by muscle biopsy.
  • Ages between 3 years and < 7 years
  • Steroid-naïve
  • Signed informed consent

Exclusion Criteria:

  • Treatment with CoenzymeQ10, creatine, amino acid supplements within 3 months of study entry
  • Treatment with cardiac medications: beta-blockers, digoxin, and carvedilol
  • Existing medical condition or physical disability that would alter subject's motor development
  • Existing medical condition that precludes the use of corticosteroids
  • Inability to swallow sample tablet in bite of soft food*
  • Investigator assessment that participant or family will not be compliant with treatment or study procedures
  • Been on investigational DMD medication for the past 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02036463

Contacts
Contact: Lauren Hache, MS lhache@childrensnational.org
Contact: Lisa Hunegs, MSW MPH lhunegs@childrensnational.org

Locations
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Nancy Kuntz, MD       nkuntz@luriechildrens.org   
Contact: Lauren Webb       lwebb@luriechildrens.org   
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Children's Research Institute
Investigators
Study Chair: Nancy Kuntz, MD Ann & Robert H Lurie Children's Hospital of Chicago
  More Information

No publications provided

Responsible Party: Nancy Kuntz, MD, Associate Professor of Neurology, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier: NCT02036463     History of Changes
Other Study ID Numbers: CINRG0513, IND #121239
Study First Received: January 6, 2014
Last Updated: January 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ann & Robert H Lurie Children's Hospital of Chicago:
Duchenne Muscular Dystrophy
Corticosteroids

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 18, 2014