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Preparing for Prevention of Huntington's Disease (PREVENT-HD) (PREVENT-HD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04818060
Recruitment Status : Not yet recruiting
First Posted : March 26, 2021
Last Update Posted : May 5, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
This is a prospective investigation which aims to address key challenges to the design of clinical trials to prevent the onset of Huntington's disease (HD). The project will provide necessary psychometric data for clinical outcome assessments (COAs) and biomarkers (BMs) in the cerebral spinal fluid (CSF) to address questions of central importance to the success of these measures for premanifest clinical trials. Of the 258 participants: 52 will be low risk of motor diagnosis, 102 high risk of motor diagnosis, 52 with diagnosed HD (stages I or II), and 52 healthy controls. Participants can expect to be on study for up to 2 years.

Condition or disease Intervention/treatment
Huntington Disease Other: Clinical Assessments Diagnostic Test: MRI Scan Diagnostic Test: Lumber Puncture (LP)

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Study Type : Observational
Estimated Enrollment : 258 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Preparing for Prevention of Huntington's Disease (PREVENT-HD)
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : February 2026
Estimated Study Completion Date : February 2026

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Low Risk of Motor Diagnosis Other: Clinical Assessments
A neurological evaluation will be administered to all participants at baseline, 1 year and 2 year follow-up visits. Motor exams and premorbid IQ assessments will be video-recorded for rater reliability assessments conducted randomly throughout the research project.

Diagnostic Test: MRI Scan
At baseline and 2 year follow-up all participants will undergo a 60-minute 3T MRI scanning session which will consist of measures of the volume of brain tissue and cerebral spinal fluid, as well as connections in the brain measuring water pathways and pictures of the brain active and at rest.

Diagnostic Test: Lumber Puncture (LP)
Participants will be asked to complete a LP at both onsite study visits (baseline and 2 year follow-up). Blood collection following the procedure will consist of about 80mL and will be stored at a repository for biomarker analysis.

High Risk of Motor Diagnosis Other: Clinical Assessments
A neurological evaluation will be administered to all participants at baseline, 1 year and 2 year follow-up visits. Motor exams and premorbid IQ assessments will be video-recorded for rater reliability assessments conducted randomly throughout the research project.

Diagnostic Test: MRI Scan
At baseline and 2 year follow-up all participants will undergo a 60-minute 3T MRI scanning session which will consist of measures of the volume of brain tissue and cerebral spinal fluid, as well as connections in the brain measuring water pathways and pictures of the brain active and at rest.

Diagnostic Test: Lumber Puncture (LP)
Participants will be asked to complete a LP at both onsite study visits (baseline and 2 year follow-up). Blood collection following the procedure will consist of about 80mL and will be stored at a repository for biomarker analysis.

Stage I or II Huntington's Disease Other: Clinical Assessments
A neurological evaluation will be administered to all participants at baseline, 1 year and 2 year follow-up visits. Motor exams and premorbid IQ assessments will be video-recorded for rater reliability assessments conducted randomly throughout the research project.

Diagnostic Test: MRI Scan
At baseline and 2 year follow-up all participants will undergo a 60-minute 3T MRI scanning session which will consist of measures of the volume of brain tissue and cerebral spinal fluid, as well as connections in the brain measuring water pathways and pictures of the brain active and at rest.

Diagnostic Test: Lumber Puncture (LP)
Participants will be asked to complete a LP at both onsite study visits (baseline and 2 year follow-up). Blood collection following the procedure will consist of about 80mL and will be stored at a repository for biomarker analysis.

Healthy Controls Other: Clinical Assessments
A neurological evaluation will be administered to all participants at baseline, 1 year and 2 year follow-up visits. Motor exams and premorbid IQ assessments will be video-recorded for rater reliability assessments conducted randomly throughout the research project.

Diagnostic Test: MRI Scan
At baseline and 2 year follow-up all participants will undergo a 60-minute 3T MRI scanning session which will consist of measures of the volume of brain tissue and cerebral spinal fluid, as well as connections in the brain measuring water pathways and pictures of the brain active and at rest.

Diagnostic Test: Lumber Puncture (LP)
Participants will be asked to complete a LP at both onsite study visits (baseline and 2 year follow-up). Blood collection following the procedure will consist of about 80mL and will be stored at a repository for biomarker analysis.




Primary Outcome Measures :
  1. Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Level [ Time Frame: baseline ]
    UHDRS Motor Diagnosis of HD Diagnostic Confidence Level is a clinical rating of how confident the movement disorder specialist is that the person has manifest HD with over 99% confidence; scale is 0-4 where 0 is 'normal' and 4 is the highest motor dysfunction.

  2. Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Level [ Time Frame: 1 years ]
    UHDRS Motor Diagnosis of HD Diagnostic Confidence Level is a clinical rating of how confident the movement disorder specialist is that the person has manifest HD with over 99% confidence; scale is 0-4 where 0 is 'normal' and 4 is the highest motor dysfunction.

  3. Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Level [ Time Frame: 2 years ]
    UHDRS Motor Diagnosis of HD Diagnostic Confidence Level is a clinical rating of how confident the movement disorder specialist is that the person has manifest HD with over 99% confidence; scale is 0-4 where 0 is 'normal' and 4 is the highest motor dysfunction.

  4. Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score [ Time Frame: baseline ]
    UHDRS Total Motor Score is a 31-item instrument each item scored on a scale of 0-4 where 0 is 'normal' and 4 is the highest motor dysfunction. Total possible range of scores is 0-124.

  5. Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score [ Time Frame: 1 year ]
    UHDRS Total Motor Score is a 31-item instrument each item scored on a scale of 0-4 where 0 is 'normal' and 4 is the highest motor dysfunction. Total possible range of scores is 0-124.

  6. Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score [ Time Frame: 2 years ]
    UHDRS Total Motor Score is a 31-item instrument each item scored on a scale of 0-4 where 0 is 'normal' and 4 is the highest motor dysfunction. Total possible range of scores is 0-124.

  7. Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity [ Time Frame: baseline ]
    UHDRS Total Functional Capacity is a clinician-rating scale of independence in activities of daily living. 13 is fully functioning and any drop in points in noted during pre-diagnosed HD.

  8. Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity [ Time Frame: 1 year ]
    UHDRS Total Functional Capacity is a clinician-rating scale of independence in activities of daily living. 13 is fully functioning and any drop in points in noted during pre-diagnosed HD.

  9. Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity [ Time Frame: 2 years ]
    UHDRS Total Functional Capacity is a clinician-rating scale of independence in activities of daily living. 13 is fully functioning and any drop in points in noted during pre-diagnosed HD.


Secondary Outcome Measures :
  1. CANTAB composite score [ Time Frame: baseline, 1 year, 2 years ]
    The Cambridge automated neuropsychological test battery (CANTAB) has a range of scores and will be summed across tasks for a composite. Higher scores will indicate better cognitive processing.

  2. Cognitive Assessment Battery (CAB) Composite Score [ Time Frame: baseline, 1 year, 2 years ]
    The CAB has a range of scores with higher scores indicative of better cognitive functions and a summed composite of the battery will be used as an outcome.

  3. Tablet Cognitive Assessment Total (TabCat) Score [ Time Frame: baseline, 1 year, 2 years ]
    The TabCat scores range across multiple tasks and the outcome will be a summed composite score across all cognitive tasks. Higher scores will indicate better cognitive processing.

  4. Problem Behavior Assessment - short form (PBA) Score [ Time Frame: baseline, 1 year, 2 years ]
    The PBA is an 11-item semi-structured instrument to assess the frequency and severity of behavioral symptoms of HD. Higher scores indicate increased severity and frequency of symptoms.


Other Outcome Measures:
  1. Exploratory Measure: Cerebral Spinal Fluid Biomarker (BM) Assessment [ Time Frame: baseline, 1 year, 2 years ]
    CSF will be processed at external labs for potential biomarkers of abnormality. CSF will be analyzed for Neurofilament light and mutant HTT.

  2. Imaging BM measured via MRI [ Time Frame: baseline, 1 year, 2 years ]
    MRI Biomarker will be the standardized volume of the basal ganglia.


Biospecimen Retention:   Samples With DNA
Cerebral spinal fluid (22mL) and blood samples (two tubes, 20mL each).


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
At baseline 258 male and female participants between the ages of 18 and 80 years will be enrolled in the study. Of the 258: 52 will be low risk of motor diagnosis, 102 high risk of motor diagnosis, 52 with diagnosed HD (stages I or II), and 52 age-, ethnicity-, and education-matched healthy controls.
Criteria

Inclusion Criteria for HD Participants:

  • Estimated at low or high probability of motor diagnosis based the multivariate risk score (MRS)
  • Willing to commit to two in-person assessment visits (baseline and 2 year follow-up) and one remote assessment (1 year follow-up)
  • No active comorbidities (i.e. receiving stable treatment)
  • All medications will be allowed although the protocol will mandate documentation of medications and analyses will particularly assess potential impact of medications on outcomes (i.e., sedation of abnormal movements)
  • CAG results must be 36 and above as measured in genetic tests already completed

Inclusion Criteria for Healthy Controls (HC):

  • Willing to commit to two in-person assessment visits (baseline and 2 year follow-up) and one remote assessment (1 year follow-up)
  • In generally good health
  • IQ > 70
  • Able to undergo an MRI scan

Exclusion Criteria (for all Participants):

  • Evidence of unstable medical or psychiatric illness (including substance abuse)
  • History of severe learning disability, mental retardation, or other central nervous system (CNS) disease or event (e.g., seizures, head trauma, additional neurological diagnoses)
  • Treatment with phenothiazine-derivative antiemetic medications such as prochlorperazine, metoclopramide, promethazine and Inapsine greater than 3 times per month
  • History of serious alcohol or drug abuse within the past year
  • Unable (determined by patient's prescribing doctor) to not take tryptophan, leucine, niacin or niacinamide-containing dietary supplements, anti-inflammatory medications, anti-coagulants (such as warfarin and heparin) or anti-platelets (such as aspirin) in the past 14 days to assure safety during lumbar puncture
  • Unable to fast (no food or drink, only water) overnight before the lumbar puncture

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04818060


Contacts
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Contact: Dace Almane, MS (608) 265-4242 almane@neurology.wisc.edu
Contact: Jane S Paulsen, PhD 319-471-3292 paulsen@neurology.wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Contact: Dace Almane, MS    608-265-4242    almane@neurology.wisc.edu   
Principal Investigator: Jane S Paulsen, PhD         
Sponsors and Collaborators
University of Wisconsin, Madison
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Jane S Paulsen, PhD University of Wisconsin, Madison
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT04818060    
Other Study ID Numbers: 2020-1175
A535100 ( Other Identifier: UW Madison )
SMPH/NEUROLOGY/NEUROLOGY ( Other Identifier: UW Madison )
Protocol Version 3/16/2021 ( Other Identifier: UW Madison )
7U01NS105509 ( U.S. NIH Grant/Contract )
7U01NS103475 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2021    Key Record Dates
Last Update Posted: May 5, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Time Frame: conclusion of study
Access Criteria: institutional certificate of professional degree

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders