A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

NCT02036463 | Withdrawn Phase 2 DMC

• 2 other identifiers: CINRG0513IND #121239
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Duchenne Muscular Dystrophy (DMD)

Keywords

Duchenne Muscular Dystrophy; Corticosteroids

Outcome Measures

Primary Outcomes (1)

• Safety

  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.

  18 months

Secondary Outcomes (2)

• Time to walk/run 50 meters

  18 months

• North Star Ambulatory Assessment (NSAA)

  18 months

Study Arms (4)

Immediate Release Prednisone

ACTIVE COMPARATOR

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

Delayed Release Prednisone

EXPERIMENTAL

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-Delayed Release Prednisone

PLACEBO COMPARATOR

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-Immediate Release Prednisone

PLACEBO COMPARATOR

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

Interventions

Prednisone DRUG

Delayed Release Prednisone; Immediate Release Prednisone; Placebo-Delayed Release Prednisone; Placebo-Immediate Release Prednisone

Placebo DRUG

Placebo-Delayed Release Prednisone; Placebo-Immediate Release Prednisone

Eligibility Criteria

• Age: 3 Years - 6 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead
• Children's National Research Institute: collaborator

Study Sites (1)

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nancy Kuntz, MD

  Ann & Robert H Lurie Children's Hospital of Chicago

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: January 6, 2014
• First Posted: January 15, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 18, 2015

Record last verified: 2015-02

Locations

US (1)