Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome

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: NCT02461420
Recruitment Status : Recruiting
First Posted : June 3, 2015
Last Update Posted : April 7, 2020
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Science (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Phelan-McDermid Syndrome Foundation
Information provided by (Responsible Party):
Mustafa Sahin, Boston Children’s Hospital

Brief Summary:
The purpose of this study is to comprehensively characterize PMS using standardized medical, cognitive, and behavioral measures and to track the natural history of the syndrome using repeated longitudinal assessments. In addition, this study will be aiming to identify biomarkers using neuroimaging, including diffusion tensor imaging and identify genetic factors which contribute to diverse phenotypes in patients with PMS.

Condition or disease
Phelan-McDermid Syndrome Autism Spectrum Disorder Intellectual Disability

Detailed Description:

Phelan-McDermid syndrome (PMS) or 22q13 Deletion syndrome, caused by a loss of one copy of the SHANK3 gene, is characterized by global developmental delay/intellectual disability, motor skills deficits, delayed or absent speech, and autism spectrum disorder. The goal of this study is to understand more about the PMS phenotype and the biological pathways associated with ID and ASD in the disorder, and to establish the foundation for future clinical trials in PMS and in other ID/ASD-associated disorders that share signaling pathways with PMS.

Individuals with PMS will be asked to participate in this study if they are 18 months or older with pathogenic deletions or mutations of the SHANK3 gene at time of enrollment, as well as healthy controls. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. Parents and unaffected siblings may also be asked to consent to have blood drawn for analysis.

The study involves 3 on site visits over 2 years. Study visits involve a physical exam, medical history questions, blood work and neuropsychological assessments. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 190 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
Study Start Date : May 2015
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025


Group/Cohort
Phelan-McDermid Syndrome
Phelan-McDermid Syndrome



Primary Outcome Measures :
  1. Change in global cognitive ability at 12 months [ Time Frame: 12 months ]
    Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability

  2. Change in adaptive behavior at 12 months [ Time Frame: 12 months ]
    Using Vineland Adaptive Behavior Scales to measure adaptive behavior

  3. Change in language abilities at 12 months [ Time Frame: 12 months ]
    Using composite of Mullen Subscales, Vineland Subscales and Macarthur Bates Communication Developmental Inventory to measure language

  4. Change in motor functioning at 12 months [ Time Frame: 12 months ]
    Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning

  5. Change in autism symptoms at 12 months [ Time Frame: 12 months ]
    Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism

  6. Change in global cognitive ability at 24 months [ Time Frame: 24 months ]
    Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability

  7. Change in adaptive behavior at 24 months [ Time Frame: 24 months ]
    Using Vineland Adaptive Behavior Scales to measure adaptive behavior

  8. Change is language abilities at 24 months [ Time Frame: 24 months ]
    Using composite of Mullen Subscales, Vineland Subscales and Macarthur Bates Communication Developmental Inventory to measure language

  9. Change in motor functioning at 24 months [ Time Frame: 24 months ]
    Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning

  10. Change in autism symptoms at 24 months [ Time Frame: 24 months ]
    Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism


Biospecimen Retention:   Samples With DNA
Blood draw for future correlative studies in the PMS Biorepository of the Developmental Synaptopathies Consortium


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
190 subjects with PMS will be enrolled across the 6 sites for this study
Criteria

Inclusion Criteria:

  • Individuals older than 18 months of age with pathogenic deletions or mutations of the SHANK3 gene
  • English speaking individuals

Exclusion Criteria:

  • Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
  • For subjects involved in imaging biomarker assessment: contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator
  • For subjects involved in EEG/ ERP biomarker assessment: contraindications to EEG/ERP, such as uncooperative or destructive behaviors preventing lead placement or capture by ERP/VEP equipment. Under age 2 or over age 11 at the time of enrollment.
  • Unwilling or unable to comply with study procedures and assessments

Information from the National Library of Medicine

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): NCT02461420


Contacts
Layout table for location contacts
Contact: Rajna Filip-Dhima, MS 617-919-7068 Rajna.Filip-Dhima@childrens.harvard.edu

Locations
Layout table for location information
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Elijah Kravets    650-724-1881    ekravets@stanford.edu   
Principal Investigator: Jon Bernstein, MD, PHD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Madison Printen    312-563-3352    Madison_T_Printen@rush.edu   
Principal Investigator: Elizabeth Berry-Kravis, MD, PhD         
Principal Investigator: Latha Soorya, PhD         
United States, Maryland
National Institutes of Health Recruiting
Bethesda, Maryland, United States, 20892
Contact: Margaret Pekar    301-402-1084    pekarm@mail.nih.gov   
Principal Investigator: Audrey Thurm, PhD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Amy Mason    617-919-3499    Amy.Mason@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD, PhD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Hannah Walker    212-241-3692    hannah.walker@mssm.edu   
Principal Investigator: Alexander Kolevzon, MD         
Sponsors and Collaborators
Boston Children’s Hospital
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Science (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Phelan-McDermid Syndrome Foundation
Investigators
Layout table for investigator information
Study Chair: Alexander Kolevzon, MD Icahn School of Medicine at Mount Sinai

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Mustafa Sahin, Assistant in Neurology, Associate Professor of Neurology, Harvard Medical School, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02461420    
Other Study ID Numbers: P00013300
1U54NS092090 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2015    Key Record Dates
Last Update Posted: April 7, 2020
Last Verified: April 2020
Keywords provided by Mustafa Sahin, Boston Children’s Hospital:
Phelan-McDermid Syndrome
PMS
Genotype
Phenotype
Natural History
Mapping
22q13 Deletion Syndrome
SHANK3
Autism Spectrum Disorder
ASD
Intellectual Disability
ID
EEG
Additional relevant MeSH terms:
Layout table for MeSH terms
Intellectual Disability
Chromosome Disorders
Syndrome
Chromosome Deletion
Autism Spectrum Disorder
Disease
Pathologic Processes
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Monosomy
Aneuploidy
Chromosome Aberrations
Congenital Abnormalities
Genetic Diseases, Inborn