A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

February 13, 2015 updated by: Nancy Kuntz, MD, Ann & Robert H Lurie Children's Hospital of Chicago

CINRG0513: A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann and Robert H. Lurie Children's Hospital of Chicago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 6 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: Placebo
Drug: Prednisone
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: Placebo
Drug: Prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 18 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to walk/run 50 meters
Time Frame: 18 months
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.
18 months
North Star Ambulatory Assessment (NSAA)
Time Frame: 18 months
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.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborators

Children's National Research Institute

Investigators

  • Study Chair: Nancy Kuntz, MD, Ann & Robert H Lurie Children's Hospital of Chicago

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

January 6, 2014

First Submitted That Met QC Criteria

January 13, 2014

First Posted (Estimate)

January 15, 2014

Study Record Updates

Last Update Posted (Estimate)

February 18, 2015

Last Update Submitted That Met QC Criteria

February 13, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CINRG0513
  • IND #121239 (Other Identifier: (FDA) IND Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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