Brain Structure and Function in Children at Risk for Huntington's Disease (Kids-HD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by University of Iowa
Sponsor:
Collaborators:
CHDI Foundation, Inc.
Information provided by (Responsible Party):
Nopoulos, Peggy C, University of Iowa
ClinicalTrials.gov Identifier:
NCT01860339
First received: May 16, 2013
Last updated: May 24, 2013
Last verified: May 2013
  Purpose

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 6-18) 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, physical and neurologic evaluation, behavioral assessment, and quantitative craniofacial structure assessment. Subjects that are gene-expanded (GE) will be compared to subjects who are gene non-expanded (GNE) and as well to matched healthy controls. Changes in brain structure and/or function in the GE group, compared to both GNE and control groups, would lend support to the notion that this disease has an important developmental component.


Condition
Huntington's Disease

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Brain Structure and Function in Children, Adolescents, and Young Adults at Risk for Huntington's Disease

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: 6-7 hour testing day ] [ Designated as safety issue: No ]
    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, the GNE group, and the healthy control 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:
  • Quantitative assessment of cognitive skills and motor skills [ Time Frame: 6-7 hour testing day ] [ Designated as safety issue: No ]
    Participants 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. Results will be analyzed for comparative differences between the GE group, the GNE group, and the healthy control 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.


Biospecimen Retention:   Samples With DNA

Biospecimens are collected and retained for both case and control participants for genetic testing purposes. Specimens are either a single sample of 1-2 teaspoons of blood drawn from the arm or 1 teaspoon of saliva via collection device.

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.


Estimated Enrollment: 400
Study Start Date: July 2005
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
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
Healthy Controls (HC)
Healthy children with no medical or psychiatric disorder and no history of HD in their family
Case Parent
Parent of participant at risk for Huntington Disease
Control Parent
Parent of healthy control participant

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Young people ages 6-18 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 6-18 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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01860339

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

Locations
United States, Iowa
University of Iowa Hospitals and Clinics, Department of Psychiatry Recruiting
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
University of Iowa
CHDI Foundation, Inc.
Investigators
Principal Investigator: Peggy C Nopoulos, MD University of Iowa
  More Information

Additional Information:
No publications provided

Responsible Party: Nopoulos, Peggy C, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01860339     History of Changes
Other Study ID Numbers: CHDI A-2920, R01NS055903
Study First Received: May 16, 2013
Last Updated: May 24, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Iowa:
Huntington's Disease
HD
Huntington Disease
Juvenile Huntington's Disease
JHD

Additional relevant MeSH terms:
Chorea
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Dyskinesias
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on October 23, 2014