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

NCT04818060 | Completed

• 6 other identifiers: 2020-1175A535100SMPH/NEUROLOGY/NEUROLOGYProtocol Version 7/17/20247U01NS1055097U01NS103475
• Study Type: observational
• Target: 258
• Locations: 1 country
• Sites: 1

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 in the study for up to 2 years.

Conditions

Huntington Disease

Keywords

biomarkers; premanifest HD; early diagnosis; motor impairment

Outcome Measures

Primary Outcomes (9)

• Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Level

  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.

  baseline

• Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Level

  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.

  1 years

• Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Level

  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 years

• Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score

  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.

  baseline

• Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score

  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.

  1 year

• Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score

  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.

  2 years

• Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity

  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.

  baseline

• Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity

  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.

  1 year

• Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity

  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.

  2 years

Secondary Outcomes (4)

• CANTAB composite score

  baseline, 1 year, 2 years

• Cognitive Assessment Battery (CAB) Composite Score

  baseline, 1 year, 2 years

• Tablet Cognitive Assessment Total (TabCat) Score

  baseline, 1 year, 2 years

• Problem Behavior Assessment - short form (PBA) Score

  baseline, 1 year, 2 years

Other Outcomes (2)

• Exploratory Measure: Cerebral Spinal Fluid Biomarker (BM) Assessment

  baseline, 1 year, 2 years

• Imaging BM measured via MRI

  baseline, 1 year, 2 years

Study Arms (4)

Low Risk of Motor Diagnosis

Approximately 52 participants who have a low probability of motor diagnosis based on the multivariate risk score.

Other: Clinical Assessments; Diagnostic Test: MRI Scan; Diagnostic Test: Lumber Puncture (LP)

High Risk of Motor Diagnosis

Approximately 102 participants who have a high probability of motor diagnosis based on the multivariate risk score.

Other: Clinical Assessments; Diagnostic Test: MRI Scan; Diagnostic Test: Lumber Puncture (LP)

Stage I or II Huntington's Disease

Approximately 52 participants who are living with diagnosed stage I or stage II Huntington's Disease.

Other: Clinical Assessments; Diagnostic Test: MRI Scan; Diagnostic Test: Lumber Puncture (LP)

Healthy Controls

Approximately 52 participants who are age-, ethnicity-, and education-matched healthy controls.

Other: Clinical Assessments; Diagnostic Test: MRI Scan; Diagnostic Test: Lumber Puncture (LP)

Interventions

Clinical Assessments OTHER

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.

Healthy Controls; High Risk of Motor Diagnosis; Low Risk of Motor Diagnosis; Stage I or II Huntington's Disease

MRI Scan DIAGNOSTIC_TEST

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.

Healthy Controls; High Risk of Motor Diagnosis; Low Risk of Motor Diagnosis; Stage I or II Huntington's Disease

Lumber Puncture (LP) DIAGNOSTIC_TEST

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; High Risk of Motor Diagnosis; Low Risk of Motor Diagnosis; Stage I or II Huntington's Disease

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Estimated at low or high probability of motor diagnosis based on the multivariate risk score (MRS)
• Willing to commit to two in-person assessment visits (baseline and 2-year follow-up) and remote assessments as needed
• 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)
• If previously measured, CAG results must be 36 or above (previous CAG is not a requirement, but this threshold will be upheld for those participants who have their CAG scores and/or have them in their medical record).
• Willing to commit to two in-person assessment visits (baseline and 2-year follow-up) and remote assessments as needed
• In generally good health
• IQ \> 70
• Able to undergo an MRI scan

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Cerebral spinal fluid (22mL) and blood samples (two tubes, 20mL each).

MeSH Terms

Conditions

Huntington Disease; Disease

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Jane S Paulsen, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 26, 2021
• Study Start: September 13, 2021
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: conclusion of study
• Access Criteria: institutional certificate of professional degree

Locations

US (1)