Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease

NCT01860339 | Completed

• 3 other identifiers: 2005077592U01NS055903-105U01NS055903-14
• Study Type: observational
• Target: 488
• Locations: 1 country
• Sites: 6

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.

Conditions

Huntington's Disease

Keywords

Huntington's Disease; HD; Huntington Disease

Outcome Measures

Primary Outcomes (1)

• Volume of brain structures as measured by Magnetic Resonance Imaging (MRI)

  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 Outcomes (1)

• Quantitative assessment of cognitive skills and behavioral factors

  4 hours out of 6-7 hour testing day, 3-4 annual visits

Other Outcomes (2)

• Quantitative assessment of motor performance

  1 hour out of 6-7 hour testing day, 3-4 annual visits

• Quantification of Neurofilament Light

  10 minutes for blood draw out of 6-7 hour testing day, 3-4 annual visits

Study Arms (2)

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

Eligibility Criteria

• Age: 6 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• 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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Peggy C Nopoulos: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (6)

University of California Davis

Sacramento, California, 95817, United States

Location

University of Iowa Hospitals and Clinics, Department of Psychiatry

Iowa City, Iowa, 52242, United States

Location

Columbia University Medical Center

New York, New York, 10027, United States

Location

Children's Hospital of Philadelphia with the University of Pennsylvania

Philadelphia, Pennsylvania, 19146, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Links

• Previous study site
• Facebook page
• Twitter account

Biospecimen

Retention: SAMPLES WITH DNA

Bio-specimens are collected and retained for all participants for genetic testing purposes and future research. Specimens are a single sample of 3-4 teaspoons of blood drawn from the arm. Optional saliva sample collection will be offered if unable to collect sufficient blood sample. 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.

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Peggy C Nopoulos, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 22, 2013
• Study Start: July 1, 2005
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)