Growth and Development of the Striatum in Huntington's Disease (Kids-HD)

• Sponsor: Peggy C Nopoulos
• Collaborators: CHDI Foundation, Inc.; National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Peggy C Nopoulos, University of Iowa

Tracking Information

• First Submitted Date: May 16, 2013
• First Posted Date: May 22, 2013
• Last Update Posted Date: June 20, 2018
• Study Start Date: July 2005
• Estimated Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 24, 2013)

Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: 6-7 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, all in consideration of age, gender, and height. Results will be evaluated for comparative differences between the GE group, the GNE group, and the healthy control 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.

Original Primary Outcome Measures (submitted: May 20, 2013)

Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Participant age of 6-18 years ]

Assessments of brain structure and function during developmental years will be evaluated for comparative differences between the GE group, the GNE group, and the healthy control group.

• Change History: Complete list of historical versions of study NCT01860339 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 24, 2013)

Quantitative assessment of cognitive skills and motor skills [ Time Frame: 6-7 hour testing day ]

Participants undergo a cognitive battery which will quantify skills such as attention, learning, memory. In addition, motor skill (both fine and gross) will be assessed and quantified. Results will be analyzed for comparative differences between the GE group, the GNE group, and the healthy control 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.

Original Secondary Outcome Measures (submitted: May 20, 2013)

Quantitative assessment of cognitive skills and motor skills [ Time Frame: Participant age 6-18 years ]

Subject undergo a cognitive battery which will quantify skills such as attention, learning, memory. In addition, motor skill (both fine and gross) will be assessed and quantified.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Growth and Development of the Striatum in Huntington's Disease
• Official Title: Growth and Development of the Striatum in Huntington's Disease

Brief 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 6-25) 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, physical and neurologic evaluation, behavioral assessment, and quantitative craniofacial structure assessment. Subjects that are gene-expanded (GE) will be compared to subjects who are gene non-expanded (GNE) and as well to matched healthy controls. Changes in brain structure and/or function in the GE group, compared to both GNE and control groups, would lend support to the notion that this disease has an important developmental component.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Bio-specimens are collected and retained for both case and control participants for genetic testing purposes. Specimens are either a single sample of 1-2 teaspoons of blood drawn from the arm or 1 teaspoon of saliva via collection device.

Biospecimens will be tested for the number of CAG repeats in the Huntingtin Gene. Each sample obtained will be coded with a randomly assigned number and never linked with personal identifiers. The results from the genetic analysis will be sent directly to the data manager on the project, who is the ONLY research member with access to this data. This person has no direct contact with study participants.

• Sampling Method: Non-Probability Sample
• Study Population: Young people ages 6-25 years old who have a parent or grandparent that has been diagnosed with Huntington's Disease
• Condition: Huntington's Disease
• Intervention: Not Provided

Study Groups/Cohorts

• Gene-expanded (GE)
  Children at risk for HD who have a CAG repeat length of 40 and above.
• Gene Non-Expanded (GNE)
  Children at risk for HD who have a CAG repeat length of 39 or less
• Healthy Controls (HC)
  Healthy children with no medical or psychiatric disorder and no history of HD in their family
• Case Parent
  Parent of participant at risk for Huntington Disease
• Control Parent
  Parent of healthy control participant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: June 18, 2018): 700
• Original Estimated Enrollment (submitted: May 20, 2013): 400
• Estimated Study Completion Date: June 30, 2019
• Estimated Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Family history of Huntington's Disease
• Age 6-25 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01860339
• Other Study ID Numbers: 200507759; 4R01NS055903-08 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Aggregate, de-identified data may be shared with approved collaborators, but individual participant data will not be shared.

• Responsible Party: Peggy C Nopoulos, University of Iowa
• Study Sponsor: Peggy C Nopoulos

Collaborators

• CHDI Foundation, Inc.
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Peggy C Nopoulos, MD; University of Iowa

• PRS Account: University of Iowa
• Verification Date: June 2018