Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease (ChANGE HD)

November 9, 2023 updated by: Peggy C Nopoulos

Growth and Development of Striatal-Cerebellum Circuitry in Subjects at Risk for Huntington's Disease

Huntington's Disease (HD) is an autosomal dominant disease manifested in a triad of cognitive, psychiatric, and motor signs and symptoms. HD is caused by a triplet repeat (CAG)expansion in the gene Huntingtin (HTT). This disease has classically been conceptualized as a neurodegenerative disease. However, recent evidence suggests that abnormal brain development may play an important role in the etiology of HD. Huntingtin (HTT)is expressed during development and through life. In animal studies, the HTT gene has been shown to be vital for brain development. This suggests that a mutant form of HTT (gene-expanded or CAG repeats of 40 and above) would affect normal brain development. In addition, studies in adults who are gene-expanded for HD, but have not yet manifested the illness, (pre-HD subjects) have significant changes in the structure of their brain, even up to 20 years before onset of clinical diagnosis. How far back these changes are evident is unknown. One possibility is that these brain changes are present throughout life, due to changes in brain development,though initially associated with only subtle functional abnormalities.

In an effort to better understand the developmental aspects of this brain disease, the current study proposes to evaluate brain structure and function in children, adolescents, and young adults (ages 6-30) who are at risk for developing HD - those who have a parent or grandparent with HD. Brain structure will be evaluating using Magnetic Resonance Imaging (MRI) with quantitative measures of the entire brain, cerebral cortex, as well as white matter integrity via Diffusion Tensor Imaging. Brain function will be assessed by cognitive tests, behavioral assessment, and physical and neurologic evaluation. Subjects that are gene-expanded (GE) will be compared to subjects who are gene non-expanded (GNE). Changes in brain structure and/or function in the GE group compared to the GNE group would lend support to the notion that this disease has an important developmental component.

Study Overview

Status

Recruiting

Study Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • California
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California Davis
        • Principal Investigator:
          • Alexandra Duffy, DO
        • Contact:
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals and Clinics, Department of Psychiatry
        • Contact:
        • Contact:
        • Principal Investigator:
          • Peggy C Nopoulos, MD
    • New York
      • New York, New York, United States, 10027
        • Recruiting
        • Columbia University Medical Center
        • Principal Investigator:
          • Ashwini Rao, EdD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19146
        • Recruiting
        • Children's Hospital of Philadelphia with the University of Pennsylvania
        • Principal Investigator:
          • Timothy Roberts, PhD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States
        • Recruiting
        • Vanderbilt University Medical Center
        • Principal Investigator:
          • Daniel Claassen, MD
        • Contact:
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas Health Science Center at Houston
        • Principal Investigator:
          • Erin Furr Stimming, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Young people ages 6-30 years old who have a parent or grandparent that has been diagnosed with Huntington's Disease

Description

Inclusion Criteria:

  • Family history of Huntington's Disease
  • Age 6-30 years
  • Age-appropriate knowledge of HD and personal risk

Exclusion Criteria:

  • Metal in body, including braces
  • History of head trauma, brain tumor, seizures, epilepsy
  • History of major surgery and/or significant ongoing medical issue(s)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Gene-expanded (GE)
Children at risk for HD who have a CAG repeat length of 40 and above.
Gene Non-Expanded (GNE)
Children at risk for HD who have a CAG repeat length of 39 or less

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volume of brain structures as measured by Magnetic Resonance Imaging (MRI)
Time Frame: 1 hour out of 6-7 hour testing day, 3-4 annual visits
Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data will be analyzed to assess brain structure based upon variables including global volume, total cerebral spinal fluid, subregion volumes, cortical surface anatomy including cortical depth, surface area and gyral shape, and symmetry between brain hemispheres, all in consideration of age, gender, and height. Results will be evaluated for comparative differences between the GE group and the GNE group. In addition, these measures of brain structure will be paired with corresponding measures of brain function to evaluate brain development based upon growth and performance.
1 hour out of 6-7 hour testing day, 3-4 annual visits

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative assessment of cognitive skills and behavioral factors
Time Frame: 4 hours out of 6-7 hour testing day, 3-4 annual visits
Participants undergo a cognitive battery which will quantify skills such as attention, learning, memory. In addition, behavioral measures will be administered in both self and proxy report formats. Results will be analyzed for comparative differences between the GE group and the GNE group. In addition, these measures of brain function will be paired with appropriate measures of brain structure to evaluate brain development based upon growth and performance.
4 hours out of 6-7 hour testing day, 3-4 annual visits

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative assessment of motor performance
Time Frame: 1 hour out of 6-7 hour testing day, 3-4 annual visits
Motor skill (both fine and gross) will be assessed and quantified via standard UHDRS motor exam and Q-Motor/Q-Cog equipment suite. Results will be analyzed for comparative differences between the GE group and the GNE group. In addition, these measures of brain function will be paired with appropriate measures of brain structure to evaluate brain development based upon growth and performance.
1 hour out of 6-7 hour testing day, 3-4 annual visits
Quantification of Neurofilament Light
Time Frame: 10 minutes for blood draw out of 6-7 hour testing day, 3-4 annual visits
Plasma samples will be sent for each visit to University College of London for analysis of NfL, an indicator of neuronal damage, to determine viability as a biomarker for Huntington's Disease.
10 minutes for blood draw out of 6-7 hour testing day, 3-4 annual visits

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Peggy C Nopoulos, MD, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2005

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

August 31, 2026

Study Registration Dates

First Submitted

May 16, 2013

First Submitted That Met QC Criteria

May 20, 2013

First Posted (Estimated)

May 22, 2013

Study Record Updates

Last Update Posted (Estimated)

November 13, 2023

Last Update Submitted That Met QC Criteria

November 9, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Aggregate, de-identified data may be shared with approved collaborators, but individual participant data will not be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Huntington's Disease

3
Subscribe