Neurobiological Predictors of Huntington's Disease (PREDICT-HD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by University of Iowa
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jane S. Paulsen, University of Iowa
ClinicalTrials.gov Identifier:
NCT00051324
First received: January 8, 2003
Last updated: December 4, 2014
Last verified: December 2014
  Purpose

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.


Condition
Huntington Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neurobiological Predictors of Huntington's Disease Trial

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • 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.



Other Outcome Measures:
  • 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.


Estimated Enrollment: 1500
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)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

People at risk for HD, who have been tested for the HD gene mutation, and who have not been diagnosed with symptoms of HD.

Criteria

Inclusion Criteria:

  • men and women at risk for HD, who have been tested for the HD gene mutation, and who have not been diagnosed with symptoms of HD (CAG ≥36 for CAG-expanded group or CAG <36 for CAG-norm group).

Exclusion Criteria:

  • diagnosis of manifest HD (at least 50% confidence by neurologist that symptoms are present);
  • clinical evidence of unstable medical or psychiatric illness (including substance abuse);
  • history of sever learning disability or mental retardation;
  • history of other CNS disease or event (e.g., seizures or head trauma);
  • current treatment with antipsychotic medications, including the traditional neuroleptics such as haloperidol as well as the atypical antipsychotics risperidone, clozapine, quetiapine, and olanzapine;
  • treatment with phenothiazine-derivative antiemetic medications such as prochlorperazine, metoclopramide, promethazine, and Inapsine on a regular basis (greater than 3 times per month);

Specific exclusion criteria for the lumbar puncture:

  • Current use of anti-coagulants
  • Current use of anti-platelets
  • Unable to provide consent for him/herself
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00051324

Contacts
Contact: Sean Thompson 319-353-4307 predict-hd@uiowa.edu

  Show 27 Study Locations
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: Jane S. Paulsen, Ph.D. University of Iowa
  More Information

Additional Information:
No publications provided

Responsible Party: Jane S. Paulsen, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT00051324     History of Changes
Other Study ID Numbers: R01NS040068, R01NS040068
Study First Received: January 8, 2003
Last Updated: December 4, 2014
Health Authority: United States: Federal Government

Keywords provided by University of Iowa:
Huntington's disease
Huntington disease
HD

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Chorea
Dementia
Dyskinesias

ClinicalTrials.gov processed this record on August 27, 2015