 |
|
Preparing for Preventive Clinical Trials
The Predict-HD Study
Jane S. Paulsen, PhD;
Michael Hayden, MD, PhD;
Julie C. Stout, PhD;
Douglas R. Langbehn, MD, PhD;
Elizabeth Aylward, PhD;
Christopher A. Ross, MD, PhD;
Mark Guttman, MD;
Martha Nance, MD;
Karl Kieburtz, MD;
David Oakes, PhD;
Ira Shoulson, MD;
Elise Kayson, MS;
Shannon Johnson, PhD;
Elizabeth Penziner, MA, MPH; and the Predict-HD Investigators of the Huntington Study Group
Arch Neurol. 2006;63:883-890.
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.
Author Affiliations: Departments of Psychiatry (Drs Paulsen and Langbehn and Ms Penziner), Neurology (Dr Paulsen), and Biostatistics (Dr Langbehn), University of Iowa, Iowa City; Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver (Dr Hayden); Department of Psychiatry, Indiana University, Bloomington (Drs Stout and Johnson); Department of Radiology, University of Washington, Seattle (Dr Aylward); Departments of Neurobiology and Psychiatry, Johns Hopkins University, Baltimore, Md (Dr Ross); Center for Addiction and Mental Health, Toronto, Ontario (Dr Guttman); Department of Neurology, University of Minnesota, St Louis Park (Dr Nance); and Center for Molecular Therapeutics, Departments of Neurology (Drs Kieburtz and Shoulson and Ms Kayson), Community and Preventive Medicine (Dr Kieburtz), Biostatistics (Dr Oakes), and Pharmacology and Medicine (Dr Shoulson), University of Rochester, Rochester, NY.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
White matter connections reflect changes in voluntary-guided saccades in pre-symptomatic Huntington's disease
Kloppel et al.
Brain 2008;131:196-204.
ABSTRACT
| FULL TEXT
Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load
Milnerwood and Raymond
J. Physiol. 2007;585:817-831.
ABSTRACT
| FULL TEXT
Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood
Runne et al.
Proc. Natl. Acad. Sci. USA 2007;104:14424-14429.
ABSTRACT
| FULL TEXT
Beyond disgust: impaired recognition of negative emotions prior to diagnosis in Huntington's disease
Johnson et al.
Brain 2007;130:1732-1744.
ABSTRACT
| FULL TEXT
Microglial activation in presymptomatic Huntington's disease gene carriers
Tai et al.
Brain 2007;130:1759-1766.
ABSTRACT
| FULL TEXT
Juvenile-Onset Huntington Disease: A Matter of Perspective
Biglan and Shoulson
Arch Neurol 2007;64:783-784.
FULL TEXT
Predictors of diagnosis in Huntington disease
Langbehn et al.
Neurology 2007;68:1710-1717.
ABSTRACT
| FULL TEXT
Genetic testing in Parkinson disease: promises and pitfalls.
Tan and Jankovic
Arch Neurol 2006;63:1232-1237.
FULL TEXT
The eyes as a window into disease prevention
Biglan and Halmagyi
Neurology 2006;67:376-377.
FULL TEXT
|
