Longitudinal Assessment of Brain Structure and Function in Juvenile-onset Huntington's Disease

Study Overview
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Brief Summary
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The goal of this observational study is to learn about brain development in Juvenile-onset Huntington's Disease (JoHD). The main questions it aims to answer are: Is brain development different in JoHD than Adult-onset Huntington's Disease (AoHD)? Can reliable biomarkers for JoHD be found in brain structure and function? Participants will be asked to complete cognitive tests, behavioral assessments, physical and neurologic evaluation, and MRI. Data collected will be compared to populations who are at-risk for HD and who have been diagnosed with HD as adults.

Detailed Description
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Huntington's disease (HD) is a genetic neurodegenerative disorder caused by an abnormal expansion of a trinucleotide CAG repeat region of the huntingtin gene (HTT). The majority of patients with HD do not present with symptoms until the age of 40-50 years old, on average, which is referred to as Adult-onset HD (AoHD). A much smaller percentage of patients with HD receive a motor diagnosis prior to the age of 21, which is referred to as Juvenile-onset HD (JoHD). Although patients with JoHD have the same core triad of cognitive, behavior, and motor symptoms, there are unique clinical characteristics that are distinct from AoHD. Specifically, patients with JoHD have less chorea compared to patients with AoHD, often presenting with rigidity and bradykinesia. However, due to the rarity, there is a lack of data regarding symptom characterization, neurobiology and progression of JoHD. Large-scale observational studies have been performed in AoHD, which have broadened our understanding of HD and opened the doors for the development and conduct of clinical trials. Patients with JoHD have been excluded from clinical trials, leaving patients and their families feeling hopeless and abandoned by the scientific community. Large-scale, longitudinal studies in patients with JoHD are critical to bettering our understanding of this devastating disease and providing hope to patients who have felt left behind as therapeutic strategies advance in AoHD. 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 have been diagnosed with JoHD. 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. This study will test the hypothesis that comprehensive and longitudinal assessments of brain function and brain structure may produce reliable biomarkers of disease progression in JoHD.

Official Title
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Longitudinal Assessment of Brain Structure and Function in Juvenile Onset Huntington's Disease (JoHD)

Conditions
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Juvenile Huntington Disease, Juvenile-Onset Huntington Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of JoHD Aged 6-30 Exclusion Criteria: Metal in body History of head trauma, brain tumor, seizures or epilepsy unrelated to JoHD History of major surgery or serious chronic medical conditions other than JoHD

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| JoHD<br>Children adolescents and young adults ages 6-30 who have been clinically diagnosed with Juvenile-onset Huntington's Disease | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 60-90 minutes out of 7-8 hour testing day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 hours out of 7-8 hour testing day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JoHD, JHD, Juvenile Huntington Disease, Juvenile Huntington's Disease, Juvenile-onset Huntington Disease