Child to Adult Neurodevelopment in Gene Expanded Huntington's Disease (ChANGE HD)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01860339|
Recruitment Status : Recruiting
First Posted : May 22, 2013
Last Update Posted : June 16, 2020
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.
|Condition or disease|
|Study Type :||Observational|
|Estimated Enrollment :||400 participants|
|Official Title:||Growth and Development of Striatal-Cerebellum Circuitry in Subjects at Risk for Huntington's Disease|
|Study Start Date :||July 2005|
|Estimated Primary Completion Date :||August 31, 2024|
|Estimated Study Completion Date :||August 31, 2024|
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
- Volume of brain structures as measured by Magnetic Resonance Imaging (MRI) [ Time Frame: 1 hour out of 6-7 hour testing day, 3-4 annual visits ]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 and the GNE 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.
- Quantitative assessment of cognitive skills and behavioral factors [ Time Frame: 4 hours out of 6-7 hour testing day, 3-4 annual visits ]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. Results will be analyzed for comparative differences between the GE group and the GNE 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.
- Quantitative assessment of motor performance [ Time Frame: 1 hour out of 6-7 hour testing day, 3-4 annual visits ]Motor skill (both fine and gross) will be assessed and quantified via standard UHDRS motor exam and Q-Motor/Q-Cog equipment suite. Results will be analyzed for comparative differences between the GE group and the GNE 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.
- Quantification of Neurofilament Light [ Time Frame: 10 minutes for blood draw out of 6-7 hour testing day, 3-4 annual visits ]Plasma samples will be sent for each visit to University College of London for analysis of NfL, an indicator of neuronal damage, to determine viability as a biomarker for Huntington's Disease.
Biospecimen Retention: Samples With DNA
Bio-specimens are collected and retained for all participants for genetic testing purposes and future research. Specimens are either a single sample of 3-4 teaspoons of blood drawn from the arm.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01860339
|Contact: Study Stafffirstname.lastname@example.org|
|Contact: Sonia K Slevinski, MSemail@example.com|
|United States, California|
|University of California Davis||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Talia Hamm, BA 916-734-6114 firstname.lastname@example.org|
|Principal Investigator: Alexandra Duffy, DO|
|United States, Iowa|
|University of Iowa Hospitals and Clinics, Department of Psychiatry||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Salomi Aladia, MA 866-514-0858 email@example.com|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10027|
|Contact: Jennifer Oscherician firstname.lastname@example.org|
|Principal Investigator: Hiral Shah, MD|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia with the University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19146|
|Contact: Jillian Lebus, MA 267-425-1136 ext 51136 email@example.com|
|Principal Investigator: Timothy Roberts, PhD|
|United States, Texas|
|University of Texas Health Science Center at Houston||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Jamie Sims, BS 713-500-7763 firstname.lastname@example.org|
|Principal Investigator: Erin Furr Stimming, MD|
|Principal Investigator:||Peggy C Nopoulos, MD||University of Iowa|