Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease
- Conditions
- Huntington's Disease
- Registration Number
- NCT01860339
- Lead Sponsor
- Peggy C Nopoulos
- 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 available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
- Family history of Huntington's Disease
- Age 6-30 years
- Age-appropriate knowledge of HD and personal risk
- Metal in body, including braces
- History of head trauma, brain tumor, seizures, epilepsy
- History of major surgery and/or significant ongoing medical issue(s)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) 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
Name Time Method Quantitative assessment of cognitive skills and behavioral factors 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.
Trial Locations
- Locations (6)
University of California Davis
🇺🇸Sacramento, California, United States
University of Iowa Hospitals and Clinics, Department of Psychiatry
🇺🇸Iowa City, Iowa, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Children's Hospital of Philadelphia with the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States