Clinical trial NCT05707663: Longitudinal Assessment of Brain Structure and Function in Juvenile-onset Huntington's Disease
Official title: Longitudinal Assessment of Brain Structure and Function in Juvenile Onset Huntington's Disease (JoHD)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Juvenile Huntington Disease
Juvenile-Onset Huntington Disease
Keywords: JoHD
JHD
Juvenile Huntington Disease
Juvenile Huntington's Disease
Juvenile-onset Huntington Disease
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Columbia University
name: University of California, Davis
name: The University of Texas Health Science Center, Houston
name: Children's Hospital of Philadelphia
name: George-Huntington-Institut GmbH
name: UCL Queen Square Institute of Neurology
First posted: 2023-02-01
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children, adolescents and young adults ages 6-30 who have been clinically diagnosed with Juvenile-onset Huntington's Disease

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Volume of brain structures as measured by Magnetic Resonance Imaging (MRI)
timeFrame: 60-90 minutes out of 7-8 hour testing day
Secondary outcomes:
measure: Quantitative assessment of cognitive skills and behavioral factors
timeFrame: 5 hours out of 7-8 hour testing day
Other outcomes:
measure: Quantitative assessment of motor performance
timeFrame: 1 hour out of 7-8 hour testing day
measure: Quantification of Neurofilament Light
timeFrame: 10 minutes for blood draw out of 7-8 hour testing day
measure: Demographic and Physiological Data
timeFrame: 10 minutes for vitals collection out of 7-8 hour testing day
Locations:
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics, Department of Psychiatry
state: Iowa
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia with the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: University of Iowa
name: Peggy C Nopoulos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nopoulos PC. Special Issue: Juvenile Onset Huntington's Disease. Brain Sci. 2020 Sep 20;10(9):652. doi: 10.3390/brainsci10090652.