Neurobiological Predictors of Huntington's Disease (PREDICT-HD)
The purpose of this trial is to study early brain and behavioral changes in people who have the gene expansion for Huntington's disease, but are currently healthy and have no symptoms.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Neurobiological Predictors of Huntington's Disease Trial|
- Refine the prediction of disease diagnosis (motor conversion) using longitudinal measures of plasma, imaging, cognitive performance, motor ratings, psychiatric and functional measures [ Time Frame: One year ] [ Designated as safety issue: No ]HD diagnosis will be better predicted by adding longitudinal change to the baseline measures of striatal and white matter volumes, tone-paced and speeded tapping score, tower moves, stroop interference and motor score.
- Improve markers of disease progression that become abnormal prior to the clinical diagnosis and to characterize their natural history. [ Time Frame: One year ] [ Designated as safety issue: No ]
Predictive models for HD diagnosis will be further improved (resulting in greater power and lower clinical trial sample size) by adding additional, sensitive measures to the PREDICT-HD exam (e.g., behavioral: companion frontal rating, cognitive: Maze test score, imaging: DTI fractional anisotropy, plasma marker: 8OHDG).
Comparisons of change rates across time will suggest measures best suited to clinical trials by large effect sizes and low variability.
- Establish the validity and reliability of disease measures identified in Outcomes 1 and 2. [ Time Frame: One year ] [ Designated as safety issue: No ]
This will require that we continuously analyze recently collected data, remove items that are insensitive, and add new items to be tested throughout the course of the study. The power and sensitivity of future multi-site trials and studies depend on accurate measures of marker validity.
HD diagnosis will be better predicted by UHDRS total motor score following new standardized reliability training and by the tapping task under modified more challenging, conditions. Psychiatric and functional ratings will be improved with item response analyses and dynamic piloting of item edits to establish the most psychometrically sound items for clinical trials.
- Cerebral spinal fluid containing unique biomarker signatures (protein and/or RNA) that are measurable prior to onset of HD clinical symptoms. [ Time Frame: One year ] [ Designated as safety issue: No ]
- Cerebral spinal fluid biomarker changes correlating with HD progression. [ Time Frame: One year ] [ Designated as safety issue: No ]
- Changes in HD cerebral spinal fluid biomarker signatures correlating with response to treatment. [ Time Frame: One year ] [ Designated as safety issue: No ]
- Levels of cerebral spinal fluid protein oxidation measured higher in HD patients prior to diagnosis, and these levels increase with neurodegeneration. [ Time Frame: One year ] [ Designated as safety issue: No ]
- Cerebral spinal fluid microRNA miR-34b expression increased in presymptomatic HD patients, and decreased in later stages of the illness. [ Time Frame: One year ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Cerebral spinal fluid acquired and retained since 2012.
Plasma retained from 2000-2007. Urine, plasma and cell lines to be acquired and retained 2008-2013.
|Study Start Date:||August 2002|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Huntington's Disease (HD) is an inherited disease that causes changes in a person's ability to control movements, thinking, and feelings. The intent of this study is to learn more about the beginning changes in thinking skills, emotional regulation, and brain structure and function as a person begins the transition from health to HD.
Preliminary studies indicate that people with HD may have marked decline before an actual diagnosis. This study will help reveal the earliest indicators of the disease and what factors influence the age at which a person carrying the gene develops the disease. It is necessary to get information on the early stages of HD in order to develop drugs that can slow or postpone the onset of HD. The investigators hope this study will provide essential information for future trials of experimental drugs for HD.
During this study, participants will undergo several detailed tests, including MRI scans of the brain, cognitive assessments, physical exams, bio specimen (blood, urine, cerebral spinal fluid) collection and neurological and psychiatric testing.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00051324
|Contact: Sean Thompsonfirstname.lastname@example.org|
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|Principal Investigator:||Jane S. Paulsen, Ph.D.||University of Iowa|