Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy (DELPHI)

This study has been completed.
Sponsor:
Information provided by:
Santhera Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00654784
First received: April 3, 2008
Last updated: July 29, 2011
Last verified: July 2011
  Purpose

Idebenone is a synthetic analogue of coenzyme Q10 and is a powerful antioxidant and essential constituent of the process of energy production on the cellular level. It can protect mitochondria from oxidative damage and boost their impaired function. It is thought that this mechanism will slow decline in heart function that is part of the disease process of Duchenne Muscular Dystrophy (DMD). It is possible that patients may benefit in terms of muscle strength and respiratory function. This pilot trial is designed to investigate this.


Condition Intervention Phase
Duchenne Muscular Dystrophy (DMD)
Drug: idebenone
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIa Double Blind, Randomised, Placebo Controlled, Single Centre Study at the University of Leuven to Assess the Efficacy and Tolerability of Idebenone in 8 - 16 Year Old Males With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Santhera Pharmaceuticals:

Primary Outcome Measures:
  • The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI). [ Time Frame: baseline and Week 52 ] [ Designated as safety issue: No ]
    • Assessing the peak systolic radial strain of the left ventricle inferolateral wall is used to characterize the cardiac involvement in the DMD patients.
    • Color Doppler Myocardial Imaging technique is used to quantify regional myocardial function.

    The cardiac involvement in DMD is characterized by degeneration, atrophy and fibrosis of the myocardium, leading to dilated cardiomyopathy. The process begins in the posterolateral wall of the left ventricle, with septal involvement appearing at later stages.



Secondary Outcome Measures:
  • Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Skeletal Muscle Strength (Upper Limb, Right and Left): Hand Grip, Elbow Flexors and Elbow Extensors (Upper Limb Score) Timed Walking Test (10 Metres) (Ambulant Patients Only) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: October 2005
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: idebenone
idebenone 450 mg/day (150 mg three times a day)
Placebo Comparator: 2 Drug: placebo

  Eligibility

Ages Eligible for Study:   8 Years to 16 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 8 - 16 years of age at time of enrolment
  • Male
  • Presence of cardiac involvement/dysfunction, defined by abnormal peak systolic strain in left ventricle (LV) inferolateral wall
  • Confirmed diagnosis of DMD (out of frame dystrophin gene deletion OR absent/<5% dystrophin protein on muscle biopsy; clinical picture consistent of typical DMD)
  • If on chronic glucocorticosteroids treatment (deflazacort, prednisone) for DMD (or any other disease) (i.e. concomitant medication): dosage must be stable (unchanged) 6 months prior to inclusion
  • If on chronic medication for DMD associated cardiomyopathy (β-blocker, diuretics): dosage must be stable (unchanged) 3 months prior to inclusion
  • Ability to provide reproducible repeat quantitative muscle testing (QMT) upper limb score within 15% of first assessment score (at Visit1/Day 1 versus Screening Visit

Exclusion Criteria:

  • Symptomatic cardiomyopathy or heart failure
  • Asymptomatic but severe cardiac dysfunction on baseline (Screening) evaluation: Fractional shortening (FS) < 20% and/or Ejection fraction (EF) < 40%
  • Use of ACE-inhibitors
  • Previous history of ventricular arrhythmias (other than isolated ventricular extrasystole); ventricular arrhythmias presented at Screening
  • Previous (6 months or less) participation in any other therapeutic trial for DMD
  • Use of coenzymeQ10, idebenone, creatine, glutamine, oxatomide, or any herbal medicines within the last 6 months
  • History of significant concomitant illness or significant impairment of renal or hepatic function
  • Known individual hypersensitivity to idebenone
  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: NCT00654784

Locations
Belgium
Children's Hospital, University Hospital
Leuven, Belgium
Sponsors and Collaborators
Santhera Pharmaceuticals
Investigators
Principal Investigator: Gunnar Buyse, MD PhD Universitaire Ziekenhuizen Leuven
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00654784     History of Changes
Other Study ID Numbers: SNT-II-001
Study First Received: April 3, 2008
Results First Received: June 7, 2011
Last Updated: July 29, 2011
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Santhera Pharmaceuticals:
Duchenne Muscular Dystrophy
DMD
Duchenne

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Idebenone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014