Growth and Development of the Striatum in Huntington's Disease (Kids-HD)

• Sponsor: Peggy C Nopoulos
• Collaborators: CHDI Foundation, Inc.; National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Peggy C Nopoulos, University of Iowa

Study Description

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 6-25) 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 or disease
Huntington's Disease

Study Design

• Study Type: Observational
• Estimated Enrollment: 700 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Growth and Development of the Striatum in Huntington's Disease
• Study Start Date: July 2005
• Estimated Primary Completion Date: June 30, 2019
• Estimated Study Completion Date: June 30, 2019

Groups and Cohorts

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
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

Outcome Measures

Primary Outcome Measures :

1. Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: 6-7 hour testing day ]
   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 :

1. Quantitative assessment of cognitive skills and motor skills [ Time Frame: 6-7 hour testing day ]
   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

Bio-specimens 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.

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Young people ages 6-25 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 6-25 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

Locations

United States, Iowa

University of Iowa Hospitals and Clinics, Department of Psychiatry

Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

Peggy C Nopoulos

CHDI Foundation, Inc.

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

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

More Information

Additional Information:

Study site 

• Responsible Party: Peggy C Nopoulos, Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT01860339 History of Changes
• Other Study ID Numbers: 200507759; 4R01NS055903-08 ( U.S. NIH Grant/Contract )
• First Posted: May 22, 2013
• Last Update Posted: June 20, 2018
• Last Verified: June 2018

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; Juvenile Huntington's Disease; JHD

Additional relevant MeSH terms:

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