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

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

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.

Study Overview

• Status: Recruiting
• Conditions: 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 Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Study Staff; Phone Number: 866-514-0858; Email: kids-johd@uiowa.edu
• Study Contact Backup: Name: Sonia Slevinski, MS; Phone Number: 3193538529; Email: sonia-slevinski@uiowa.edu

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • Not yet recruiting
      • University of California Davis
      • Principal Investigator: Alexandra Duffy, DO
      • Contact: Raj Tsutsui, BS; Phone Number: 916-734-6278; Email: rajsin@ucdavis.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics, Department of Psychiatry
      • Principal Investigator: Peggy C Nopoulos, MD
      • Contact: Keara Turkington, BA; Phone Number: 866-514-0858; Email: kids-johd@uiowa.edu
  • New York
    • New York, New York, United States, 10027
      • Not yet recruiting
      • Columbia University Medical Center
      • Principal Investigator: Ashwini Rao, EdD
      • Contact: Mia Parker; Email: mnp2135@cumc.columbia.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Not yet recruiting
      • Children's Hospital of Philadelphia with the University of Pennsylvania
      • Principal Investigator: Timothy Roberts, PhD
      • Contact: Shana Ward, BS; Phone Number: 267-425-1136; Email: wardsh@chop.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Not yet recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Daniel Claassen, MD
      • Contact: Isabelle Taylor, BS; Phone Number: 615-875-1539; Email: Isabelle.taylor@vumc.org
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • University of Texas Health Science Center at Houston
      • Principal Investigator: Erin Furr Stimming, MD
      • Contact: Brittany Duncan, BS; Phone Number: 712-486-3134; Email: Brittany.J.Duncan@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
JoHD; Children adolescents and young adults ages 6-30 who have been clinically diagnosed with Juvenile-onset Huntington's Disease

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 hour out of 7-8 hour testing day
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 determine viability as a biomarker for Huntington's Disease.	10 minutes for blood draw out of 7-8 hour testing day
Demographic and Physiological Data	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.	10 minutes for vitals collection out of 7-8 hour testing day

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: The University of Texas Health Science Center, Houston; Children's Hospital of Philadelphia; Columbia University; University of California, Davis; UCL Queen Square Institute of Neurology; George-Huntington-Institut GmbH
• Investigators: Principal Investigator: Peggy C Nopoulos, MD, University of Iowa

Publications and helpful links

General Publications

• Nopoulos PC. Special Issue: Juvenile Onset Huntington's Disease. Brain Sci. 2020 Sep 20;10(9):652. doi: 10.3390/brainsci10090652.

Helpful Links

• Study site
• Study site
• Study site

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: January 21, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Juvenile Huntington's Disease; JoHD; JHD; Juvenile Huntington Disease; Juvenile-onset Huntington Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: 201109879

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregate, de-identified data may be shared with approved collaborators, but individual participant data will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No