Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA)

Am Heart J. 2011 Mar;161(3):639-645.e1. doi: 10.1016/j.ahj.2010.10.038. Epub 2011 Jan 31.

Abstract

Background: Friedreich ataxia (FRDA) is commonly associated with hypertrophic cardiomyopathy, but little is known about its frequency, severity, or treatment. In this 6-month randomized, double-blind, controlled study, we sought to determine whether idebenone improves cardiac measures in FRDA.

Methods: Seventy pediatric subjects were treated either with idebenone (450/900 mg/d or 1,350/2,250 mg/d) or with placebo. Electrocardiograms (ECGs) were assessed at each visit, and echocardiograms, at baseline and week 24.

Results: We found ECG abnormalities in 90% of the subjects. On echocardiogram, 81.4% of the total cohort had left ventricular (LV) hypertrophy, as measured by increased LV mass index-Dubois, and the mean ejection fraction (EF) was 56.9%. In linear regression models, longer PR intervals at baseline were marginally associated with longer GAA repeat length (P = .011). Similarly, GAA repeat length did not clearly predict baseline EF (P = .086) and LV mass by M-mode (P = .045). Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group.

Conclusions: Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA. The present study does not provide evidence of benefit in this cohort over a 6-month treatment period.

Trial registration: ClinicalTrials.gov NCT00537680.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Cardiomyopathy, Hypertrophic / complications
  • Cardiomyopathy, Hypertrophic / diagnostic imaging
  • Cardiomyopathy, Hypertrophic / drug therapy*
  • Cardiomyopathy, Hypertrophic / physiopathology
  • Child
  • Clinical Trials, Phase III as Topic
  • Double-Blind Method
  • Echocardiography, Doppler
  • Electrocardiography
  • Female
  • Friedreich Ataxia / complications
  • Friedreich Ataxia / drug therapy*
  • Friedreich Ataxia / physiopathology
  • Humans
  • Hypertrophy, Left Ventricular / drug therapy
  • Male
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology
  • Ubiquinone / therapeutic use
  • Ventricular Function / drug effects

Substances

  • Antioxidants
  • Ubiquinone
  • idebenone

Associated data

  • ClinicalTrials.gov/NCT00537680