Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease

Huntington's Disease Clinical Trial

— ChANGE HD  

Official title:

Growth and Development of Striatal-Cerebellum Circuitry in Subjects at Risk for Huntington's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01860339
• Other study ID #: 200507759
• Secondary ID: 2U01NS055903-10
• Status: Recruiting
• Start date: July 2005
• Est. completion date: August 31, 2026

Study information

• Verified date: November 2023
• Source: University of Iowa
• Contact: Study Staff
• Phone: 866-514-0858
• Email: change-hd[@]uiowa.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: August 31, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 30 Years

Eligibility

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)

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Locations

Country	Name	City	State
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Iowa Hospitals and Clinics, Department of Psychiatry	Iowa City	Iowa
United States	Vanderbilt University Medical Center	Nashville	Tennessee
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	University of California Davis	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
Peggy C Nopoulos	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quantitative assessment of motor performance	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.	1 hour out of 6-7 hour testing day, 3-4 annual visits
Other	Quantification of Neurofilament Light	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.	10 minutes for blood draw out of 6-7 hour testing day, 3-4 annual visits
Primary	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	Quantitative assessment of cognitive skills and behavioral factors	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.	4 hours out of 6-7 hour testing day, 3-4 annual visits

External Links

•   Current study site
•   Facebook page
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•   Twitter account