Journal article
Utility of the Huntington's Disease Prognostic Index Score for a Perimanifest Clinical Trial
Movement disorders, Vol.37(5), pp.1040-1046
02/16/2022
DOI: 10.1002/mds.28944
PMCID: PMC9306552
PMID: 35170086
Abstract
Subtle neurodegenerative motor and cognitive impairments accumulate over a prodromal period several years before clinical diagnosis of Huntington's disease (HD). The inclusion of prodromal individuals in therapeutic trials would facilitate testing of therapies early in the disease course and the development of treatments intended to prevent or delay disability.
We evaluate the normalized prognostic index (PIN) score as a tool to select participants for a perimanifest trial. We explore anticipated PIN-based inclusion rates from the preHD screening population and estimate sample-size requirements based on PIN threshold, trial duration, and outcome measure.
Individual participant data from ENROLL-HD were used to fit mixed effect linear models to assess longitudinal changes in clinical metrics for participants with early-manifest HD and PIN-stratified preHD subcohorts.
A PIN threshold of 0.0 was met by 40% of the preHD participants in ENROLL-HD; 39.4% and 55.2% progressed to new diagnoses of early-manifest HD within 2 and 3 years, respectively. Various PIN thresholds also enabled the selection of specified ratios of prodromal preHD to early manifest HD participants for a perimanifest trial. Estimated sample sizes for a trial enrolling prodromal preHD (PIN > 0.0) and stage 1 and 2 motor-diagnosed participants varied depending on the composition of the screening pool, the length of follow-up (1, 2, or 3 years), and outcome measure.
The composition of a perimanifest clinical trial population can be defined using preselected PIN thresholds, facilitating the assessment of potential disease-modifying therapies in HD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Details
- Title: Subtitle
- Utility of the Huntington's Disease Prognostic Index Score for a Perimanifest Clinical Trial
- Creators
- Douglas R Langbehn - Department of Psychiatry, University of Iowa Carver College of Medicine, Psychiatry Research, Iowa City, Iowa, USAElisabeth M Fine - Voyager Therapeutics, Inc., Cambridge, Massachusetts, USAAndreas Meier - Voyager Therapeutics, Inc., Cambridge, Massachusetts, USASteven Hersch - Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Resource Type
- Journal article
- Publication Details
- Movement disorders, Vol.37(5), pp.1040-1046
- DOI
- 10.1002/mds.28944
- PMID
- 35170086
- PMCID
- PMC9306552
- NLM abbreviation
- Mov Disord
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Language
- English
- Date published
- 02/16/2022
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984216743002771
Metrics
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