Preparing for preventive clinical trials: the Predict-HD study.

Full 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).

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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Author information

Author/s: Paulsen, Jane S (JS); Hayden, Michael (M); Stout, Julie C (JC); Langbehn, Douglas R (DR); Aylward, Elizabeth (E); Ross, Christopher A (CA); Guttman, Mark (M); Nance, Martha (M); Kieburtz, Karl (K); Oakes, David (D); Shoulson, Ira (I); Kayson, Elise (E); Johnson, Shannon (S); Penziner, Elizabeth (E); Predict-HD Investigators of the Huntington Study Group;

Affiliation: Department of Psychiatry, University of Iowa, Iowa City 52242-1000, USA. jane-paulsen(-atsign-)uiowa.edu

Grants: 00059 (Agency:PHS HHS) ; 01579 (Agency:PHS HHS) ; 16375 (Agency:PHS HHS) ; 40068 (Agency:PHS HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Archives of neurology (Arch Neurol), published in United States. (Language: eng)

Reference: 2006-Jun; vol 63 (issue 6) : pp 883-90

Dates: Created 2006/06/13; Completed 2006/07/26; Revised 2007/11/14;

PMID: 16769871, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Age Factors
DNA Mutational Analysis
Female
Humans
Huntington Disease - diagnosis; genetics; physiopathology
International Cooperation
Longitudinal Studies

Longitudinal Studies
Magnetic Resonance Imaging - methods
Male
Middle Aged
Neurologic Examination
Neuropsychological Tests - statistics & numerical data
Probability
Trinucleotide Repeats - genetics

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