Clinical trials are underway to slow disease progression in patients with Huntington disease (HD) with manifest disease. It is conceivable, therefore, that treatments could be instituted that would delay the development of symptoms. Two crucial clinical questions must be answered before trials of preventive therapies can begin: When should treatment begin? How can treatment efficacy be measured? Preliminary studies suggest that magnetic resonance (MR) imaging and neuropsychological measures show significant decline before the diagnosis of HD. The identification of markers for HD onset would advance the design of clinical trials to delay onset or slow progression in presymptomatic HD in the following ways: (1) Marker data will be available for establishing reliable, valid, and practical measures of efficacy for experimental therapeutics. (2) Target samples will be smaller and better refined, allowing more robust hypothesis testing and minimization of therapeutic risk vs benefit ratios. This study, the Neurobiological Predictors in Huntington's Disease (PREDICT-HD) study, will follow up 600 individuals at risk for HD at 20 research sites in North America. Every visit will involve standardized ratings of motor, cognitive, functional, and psychiatric signs in HD. A more comprehensive evaluation at baseline and 24 and 48 months will involve MR imaging and neuropsychological assessment. All subjects will be aged 30 to 55 years and without symptoms of manifest HD or other significant medical or psychiatric illness. Imaging analyses will emphasize measures of basal ganglia. Neuropsychological measures will emphasize tasks sensitive to basal ganglia circuitry. Analyses will compare rates of change in MR imaging volume and cognitive performances between at-risk persons with and without CAG expansion. Survival analyses will assess the utility of MR imaging and neuropsychological variables as predictors of clinical HD diagnosis. Their interrelationships with CAG length and potential confounders such as education will be controlled for and characterized. A detailed quantitative description of prediagnostic and peridiagnostic decline on these measures will be the subject of the secondary analyses.
Shoulson I. PREDICT-HD: Markers Identifying Individuals at Risk for Huntington Disease. Arch Neurol. 2001;58(8):1317. doi: