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

Sponsor

University of Iowa (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05707663

Collaborator

Columbia University (Other), University of California, Davis (Other), The University of Texas Health Science Center, Houston (Other), Children's Hospital of Philadelphia (Other), George-Huntington-Institut GmbH (Other), UCL Queen Square Institute of Neurology (Other)

Enrollment

Locations

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Huntington Disease Juvenile-Onset Huntington Disease

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Aug 31, 2025

Anticipated Study Completion Date :

Aug 31, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [60-90 minutes out of 7-8 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.

Secondary Outcome Measures

Quantitative assessment of cognitive skills and behavioral factors [5 hours out of 7-8 hour testing day]
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.

Other Outcome Measures

Quantitative assessment of motor performance [1 hour out of 7-8 hour testing day]
Motor skill (both fine and gross) will be assessed and quantified via standard UHDRS motor exam and Q-Motor/Q-Cog equipment suite.
Quantification of Neurofilament Light [10 minutes for blood draw out of 7-8 hour testing day]
Plasma samples will be sent for each visit to University College of London for analysis of NfL, an indicator of neuronal damage determine viability as a biomarker for Huntington's Disease.
Demographic and Physiological Data [10 minutes for vitals collection out of 7-8 hour testing day]
Analyses will control for age, sex and height/weight. Age will be recorded in whole months. Sex will be recorded as gender assigned at birth with current gender identity noted. Height will be measured in centimeters, and weight will be measured in kilograms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis	Sacramento	California	United States	95817
2	University of Iowa Hospitals and Clinics, Department of Psychiatry	Iowa City	Iowa	United States	52242
3	Columbia University Medical Center	New York	New York	United States	10027
4	Children's Hospital of Philadelphia with the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19146
5	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030