Measuring the rate of progression in Friedreich ataxia: implications for clinical trial design

Mov Disord. 2010 Mar 15;25(4):426-32. doi: 10.1002/mds.22912.

Abstract

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, and arreflexia. A variety of measures are currently used to quantify disease progression, including the Friedreich Ataxia Rating Scale, examiner-rated functional disability scales, self-reported activities of daily living and performance measures such as the timed 25-foot walk, 9-hole pegboard test, PATA speech test, and low-contrast letter acuity vision charts. This study examines the rate of disease progression over one and two years in a cohort of 236 Friedreich ataxia patients using these scales and performance measure composites. The Friedreich Ataxia Rating Scale and performance-measure composites captured disease progression, with a greater sensitivity to change over 2 years than over 1 year. The measures differed in their sensitivity to change and in possible bias. These results help to establish norms for progression in FRDA that can be useful in measuring the long-term success of therapeutic agents and defining sample-size calculations for double-blind clinical trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Adult
  • Aged
  • Clinical Trials as Topic
  • DNA, Mitochondrial / genetics
  • Disease Progression
  • Double-Blind Method
  • Female
  • Friedreich Ataxia / diagnosis*
  • Friedreich Ataxia / genetics
  • Friedreich Ataxia / physiopathology*
  • Humans
  • Iron-Binding Proteins / genetics
  • Male
  • Middle Aged
  • Neurologic Examination
  • Point Mutation / genetics
  • Severity of Illness Index
  • Speech Disorders / diagnosis
  • Trinucleotide Repeats / genetics
  • Walking
  • Young Adult

Substances

  • DNA, Mitochondrial
  • Iron-Binding Proteins
  • frataxin