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

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ClinicalTrials.gov Identifier: NCT01860339
Recruitment Status : Recruiting
First Posted : May 22, 2013
Last Update Posted : February 18, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Peggy C Nopoulos, University of Iowa

Tracking Information
First Submitted Date May 16, 2013
First Posted Date May 22, 2013
Last Update Posted Date February 18, 2021
Actual Study Start Date July 2005
Estimated Primary Completion Date August 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 19, 2019)
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.
Original Primary Outcome Measures
 (submitted: May 20, 2013)
Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Participant age of 6-18 years ]
Assessments of brain structure and function during developmental years will be evaluated for comparative differences between the GE group, the GNE group, and the healthy control group.
Change History
Current Secondary Outcome Measures
 (submitted: December 19, 2019)
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.
Original Secondary Outcome Measures
 (submitted: May 20, 2013)
Quantitative assessment of cognitive skills and motor skills [ Time Frame: Participant age 6-18 years ]
Subject undergo a cognitive battery which will quantify skills such as attention, learning, memory. In addition, motor skill (both fine and gross) will be assessed and quantified.
Current Other Pre-specified Outcome Measures
 (submitted: December 19, 2019)
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease
Official Title Growth and Development of Striatal-Cerebellum Circuitry in Subjects at Risk for Huntington's Disease
Brief Summary

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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:

Bio-specimens are collected and retained for all participants for genetic testing purposes and future research. Specimens are either a single sample of 3-4 teaspoons of blood drawn from the arm.

Biospecimens will be tested for the number of CAG repeats in the Huntingtin Gene. Each sample obtained will be coded with a randomly assigned number and never linked with personal identifiers. The results from the genetic analysis will be sent directly to the data manager on the project, who is the ONLY research member with access to this data. This person has no direct contact with study participants.

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
Condition Huntington's Disease
Intervention Not Provided
Study Groups/Cohorts
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 20, 2013)
400
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 31, 2024
Estimated Primary Completion Date August 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria

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)
Sex/Gender
Sexes Eligible for Study: All
Ages 6 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Study Staff 866-514-0858 kids-hd@uiowa.edu
Contact: Sonia K Slevinski, MS 319-353-8529 sonia-slevinski@uiowa.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01860339
Other Study ID Numbers 200507759
2U01NS055903-10 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: Aggregate, de-identified data may be shared with approved collaborators, but individual participant data will not be shared.
Responsible Party Peggy C Nopoulos, University of Iowa
Study Sponsor Peggy C Nopoulos
Collaborators National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Peggy C Nopoulos, MD University of Iowa
PRS Account University of Iowa
Verification Date February 2021