TY - JOUR
T1 - Preparing for preventive clinical trials
T2 - The predict-HD study
AU - Paulsen, Jane S.
AU - Hayden, Michael
AU - Stout, Julie C.
AU - Langbehn, Douglas R.
AU - Aylward, Elizabeth
AU - Ross, Christopher A.
AU - Guttman, Mark
AU - Nance, Martha
AU - Kieburtz, Karl
AU - Oakes, David
AU - Shoulson, Ira
AU - Kayson, Elise
AU - Johnson, Shannon
AU - Penziner, Elizabeth
PY - 2006
Y1 - 2006
N2 - 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). Design: 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. Setting: Genetics and HD outpatient clinics. Participants: 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. Main Outcome Measures: 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.
AB - 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). Design: 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. Setting: Genetics and HD outpatient clinics. Participants: 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. Main Outcome Measures: 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.
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U2 - 10.1001/archneur.63.6.883
DO - 10.1001/archneur.63.6.883
M3 - Article
C2 - 16769871
AN - SCOPUS:33745110056
SN - 0003-9942
VL - 63
SP - 883
EP - 890
JO - Archives of Neurology
JF - Archives of Neurology
IS - 6
ER -