title: Preparing for preventive clinical trials: the Predict-HD study.
abstract: BACKGROUND
  The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown.
  
  
  OBJECTIVE
  To examine measures that may be associated with disease in the largest cohort ever recruited of prediagnosed individuals carrying the gene expansion for Huntington disease (HD).
  
  
  METHODS
  The Predict-HD study is a multicenter observational research study in progress at 17 sites in the United States, 4 in Canada, and 3 in Australia.
  
  
  METHODS
  Genetics and HD outpatient clinics.
  
  
  METHODS
  Five hundred five at-risk individuals who had previously undergone elective DNA analyses for the CAG expansion in the HD gene (predictive testing) and did not currently have a clinical diagnosis of HD.
  
  
  METHODS
  Basal ganglia volumes on magnetic resonance images, estimated probability of diagnosis (based on CAG repeat length), performances on 21 standardized cognitive tasks, total scores on 3 scales of psychiatric distress, and motor diagnosis based on the Unified Huntington's Disease Rating Scale.
  
  
  RESULTS
  Several variables showed progressive decline as the diagnostic ratings advanced toward manifest disease. Estimated probability of diagnosis was associated with Unified Huntington's Disease Rating Scale prediagnostic stages and varied from 15% in persons with no motor abnormalities to nearly 40% in those with abnormalities suggestive of probable disease. Striatal volumes, cognitive performances, and even psychiatric ratings declined significantly with motor manifestations of disease.
  
  
  CONCLUSIONS
  The documentation of biological and refined clinical markers suggests several clinical end points for preventive clinical trials. Longitudinal study is critical to further validate possible markers for prediagnosed HD.
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City 52242-1000, USA. jane-paulsen@uiowa.edu
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.forename: Michael
authors.initials: M
authors.lastname: Hayden
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Langbehn
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Aylward
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Mark
authors.initials: M
authors.lastname: Guttman
authors.forename: Martha
authors.initials: M
authors.lastname: Nance
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.forename: David
authors.initials: D
authors.lastname: Oakes
authors.forename: Ira
authors.initials: I
authors.lastname: Shoulson
authors.forename: Elise
authors.initials: E
authors.lastname: Kayson
authors.forename: Shannon
authors.initials: S
authors.lastname: Johnson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Penziner
mesh_terms: D000328:Adult; D000367:Age Factors; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D007391:International Cooperation; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011336:Probability; D018911:Trinucleotide Repeats / Q000235:genetics*