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

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

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Drug: placebo; Drug: idebenone

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • Children's Hospital, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: idebenone; idebenone 450 mg/day (150 mg three times a day)
Placebo Comparator: 2	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF)	1 year
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)	1 year
Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG.	1 year

Collaborators and Investigators

• Sponsor: Santhera Pharmaceuticals
• Investigators: Principal Investigator: Gunnar Buyse, MD PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Buyse GM, Goemans N, van den Hauwe M, Thijs D, de Groot IJ, Schara U, Ceulemans B, Meier T, Mertens L. Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial. Neuromuscul Disord. 2011 Jun;21(6):396-405. doi: 10.1016/j.nmd.2011.02.016. Epub 2011 Mar 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: April 3, 2008
• First Submitted That Met QC Criteria: April 3, 2008
• First Posted (Estimate): April 9, 2008

Study Record Updates

• Last Update Posted (Estimate): August 1, 2011
• Last Update Submitted That Met QC Criteria: July 29, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; DMD; Duchenne
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Idebenone
• Other Study ID Numbers: SNT-II-001