Clinical trial NCT01860339: Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease
Official title: Growth and Development of Striatal-Cerebellum Circuitry in Subjects At Risk for Huntington's Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Huntington's Disease
Keywords: Huntington's Disease
HD
Huntington Disease
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2013-05-22
Enrollment: 400
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Young people ages 6-30 years old who have a parent or grandparent that has been diagnosed with 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 6-30) 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, behavioral assessment, and physical and neurologic evaluation. Subjects that are gene-expanded (GE) will be compared to subjects who are gene non-expanded (GNE). Changes in brain structure and/or function in the GE group compared to the GNE group would lend support to the notion that this disease has an important developmental component.


Eligibility criteria: Inclusion Criteria:

* Family history of Huntington's Disease
* Age 6-30 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)

Primary outcomes:
measure: Volume of brain structures as measured by Magnetic Resonance Imaging (MRI)
timeFrame: 1 hour out of 6-7 hour testing day, 3-4 annual visits
Secondary outcomes:
measure: Quantitative assessment of cognitive skills and behavioral factors
timeFrame: 4 hours out of 6-7 hour testing day, 3-4 annual visits
Other outcomes:
measure: Quantitative assessment of motor performance
timeFrame: 1 hour out of 6-7 hour testing day, 3-4 annual visits
measure: Quantification of Neurofilament Light
timeFrame: 10 minutes for blood draw out of 6-7 hour testing day, 3-4 annual visits
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: