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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 : June 16, 2020
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Peggy C Nopoulos, University of Iowa

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.


Condition or disease
Huntington's Disease

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Growth and Development of Striatal-Cerebellum Circuitry in Subjects at Risk for Huntington's Disease
Study Start Date : July 2005
Estimated Primary Completion Date : August 31, 2024
Estimated Study Completion Date : August 31, 2024


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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.

  2. 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.


Biospecimen Retention:   Samples With DNA

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.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
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)

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): NCT01860339


Contacts
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Contact: Study Staff 866-514-0858 kids-hd@uiowa.edu
Contact: Sonia K Slevinski, MS 319-353-8529 sonia-slevinski@uiowa.edu

Locations
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United States, California
University of California Davis Recruiting
Sacramento, California, United States, 95817
Contact: Talia Hamm, BA    916-734-6114    tghamm@ucdavis.edu   
Principal Investigator: Alexandra Duffy, DO         
United States, Iowa
University of Iowa Hospitals and Clinics, Department of Psychiatry Recruiting
Iowa City, Iowa, United States, 52242
Contact: Salomi Aladia, MA    866-514-0858    change-hd@uiowa.edu   
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10027
Contact: Jennifer Oscherician       jmo2169@cumc.columbia.edu   
Principal Investigator: Hiral Shah, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia with the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19146
Contact: Jillian Lebus, MA    267-425-1136 ext 51136    azorlosaj@email.chop.edu   
Principal Investigator: Timothy Roberts, PhD         
United States, Texas
University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Jamie Sims, BS    713-500-7763    jamie.sims@uth.tmc.edu   
Principal Investigator: Erin Furr Stimming, MD         
Sponsors and Collaborators
Peggy C Nopoulos
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Peggy C Nopoulos, MD University of Iowa
Additional Information:
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Responsible Party: Peggy C Nopoulos, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01860339    
Other Study ID Numbers: 200507759
2U01NS055903-10 ( U.S. NIH Grant/Contract )
First Posted: May 22, 2013    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: January 2020
Individual Participant Data (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.
Keywords provided by Peggy C Nopoulos, University of Iowa:
Huntington's Disease
HD
Huntington Disease
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