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

Duchenne Muscular Dystrophy (DMD) Clinical Trial

— DELPHI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00654784
• Other study ID #: SNT-II-001
• Status: Completed
• Phase: Phase 2
• First received: April 3, 2008
• Last updated: July 29, 2011
• Start date: October 2005
• Est. completion date: August 2007

Study information

• Verified date: July 2011
• Source: Santhera Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 8 Years to 16 Years

Eligibility

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 (ß-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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy (DMD)
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• idebenone
idebenone 450 mg/day (150 mg three times a day)
• placebo

Locations

Country	Name	City	State
Belgium	Children's Hospital, University Hospital	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Santhera Pharmaceuticals

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF)		1 year	No
Secondary	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	No
Secondary	Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG.		1 year	Yes