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RASopathy Biorepository

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ClinicalTrials.gov Identifier: NCT04395495
Recruitment Status : Recruiting
First Posted : May 20, 2020
Last Update Posted : March 11, 2022
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Study Description
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The RASopathies are a group of developmental disorders caused by genetic changes in the genes that compose the Ras/mitogen activated protein kinase (MAPK) pathway. New RASopathies are being diagnosed frequently. This pathway is essential in the regulation of the cell cycle and the determination of cell function. Thus, appropriate function of this pathway is critical to normal development. Each syndrome in this group of disorders has unique phenotypic features, but there are many overlapping features including facial features, heart defects, cutaneous abnormalities, cognitive delays, and a predisposition to malignancies. This research study proposes to collect and store human bio-specimens from patients with suspected or diagnosed RASopathies. Once obtained, blood and/or tissue samples will be processed for: metabolic function studies, biomarkers, genetic studies, and/or the establishment of immortalized cell lines. In addition, data from the medical record (including neuropsychological evaluations) and surveys will be stored to create a longitudinal database for research conducted at CCHMC or at other research institutions.

Condition or disease
RAS Mutation Neurofibromatosis 1 Noonan Syndrome Noonan Syndrome With Multiple Lentigines Noonan Neurofibromatosis Syndrome Cardiofaciocutaneous Syndrome Costello Syndrome Legius Syndrome Smith-Kingsmore Syndrome MTOR Gene Mutation GATOR-1 Gene Mutation SYNGAP1-Related Intellectual Disability DLG4 MAPK1 Gene Mutation

Detailed Description:

Patients who are being evaluated for a RASopathy may have overlapping features, but the disorders individually can be exceedingly rare and many are not yet well characterized. Additionally, available clinical testing is not always diagnostic in this group of patients. The investigators propose to study disorders across the RAS/MAPK pathway, identifying both commonalities and differences, under one unified ongoing research protocol. The investigators propose:

  1. To investigate the metabolic and molecular basis of established and suspected RASopathies.
  2. Collect specimens derived from blood, buccal cells, sputum, urine, bone marrow, tumor tissue and residual specimens, including but not limited to pleural fluid, ascetic fluid, chyle, skin, lung, lymphatic or renal tissue and/or bronchoalveolar lavage fluid, tissue specimens, and/or cells that are left over from clinical procedures from enrolled patients for research purposes only.
  3. Non-invasive or minimally invasive procedures to collect tissues for research purposes only, such as saliva, skin, or blood samples are also allowed. The collection of all samples from minor subjects will be done only if it is safe for the participant. Clinical studies will take precedence over research procedures.
  4. Collect demographic information, medical history, and clinical test results to create a longitudinal research database of participants with suspected or diagnosed RASopathies. Participants will also complete surveys to be included in the research database (see "Research Database" section for details).
  5. Provide a facility for long-term storage of bio-specimens and clinical data from participants with suspected or diagnosed RASopathies and their unaffected relatives.
Study Design
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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 50 Years
Official Title: Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies.
Actual Study Start Date : June 27, 2017
Estimated Primary Completion Date : December 2065
Estimated Study Completion Date : December 2065

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
Neurofibromatosis 1 (NF1)
Individuals with a confirmed or suspected diagnosis of Neurofibromatosis Type 1 (NF1). Diagnosis may be made clinically and/or confirmed through genetic testing. Clinical (non-genetic) diagnosis requires that individuals meet the National Institute of Health's (NIH) clinical diagnostic criteria for NF1.
Noonan Syndrome
Individuals with a confirmed or suspected diagnosis of Noonan Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.
Noonan Syndrome with Multiple Lentigines
Individuals with a confirmed or suspected diagnosis of Noonan Syndrome with Multiple Lentigines. Diagnosis may be made clinically and/or confirmed through genetic testing.
Noonan Neurofibromatosis Syndrome
Individuals with a confirmed or suspected diagnosis of Noonan Neurofibromatosis Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.
Cardiofaciocutaneous Syndrome
Individuals with a confirmed or suspected diagnosis of Cardiofaciocutaneous Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.
Costello Syndrome
Individuals with a confirmed or suspected diagnosis of Costello Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.
Legius Syndrome
Individuals with a confirmed or suspected diagnosis of Legius Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.
Smith-Kingsmore Syndrome
Individuals with a confirmed or suspected diagnosis of Smith-Kingsmore Syndrome. Diagnosis may be made clinically and/or confirmed through genetic testing.
GATOR-1 Mutation
Individuals with a suspected or known mutation of GATOR-1.
SYNGAP1-Related Intellectual Disability
Individuals with a suspected or known mutation of SYNGAP1.
DLG4 Mutation
Individuals with a suspected or known mutation of DLG4.
MAPK1 Gene Mutation
Individuals with a suspected or known mutation of MAPK1.
MTOR Gene Mutation
  1. Individuals with a suspected or known mutation of a gene associated with the MTOR cellular pathway. Diagnosis may be made clinically and/or confirmed through genetic testing.
  2. Unaffected relatives of individuals with a suspected or known mutation of a gene associated with the MTOR cellular pathway.
RAS Mutation
  1. Individuals with a suspected or known mutation of a gene associated with the RAS/MAPK cellular pathway. Diagnosis may be made clinically and/or confirmed through genetic testing.
  2. Unaffected relatives of individuals with a suspected or known mutation of a gene associated with the RAS/MAPK cellular pathway.


Outcome Measures
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Primary Outcome Measures :
  1. Collection of biospecimen [ Time Frame: 50 years ]
    Collect specimens derived from blood, buccal cells, sputum, urine, bone marrow, tumor tissue and residual specimens, including but not limited to pleural fluid, ascetic fluid, chyle, skin, lung, lymphatic or renal tissue and/or bronchoalveolar lavage fluid, tissue specimens, and/or cells that are left over from clinical procedures from enrolled patients for research purposes only.

  2. Collection of medical history [ Time Frame: 50 years ]
    Collect demographic information, medical history, and clinical test results to create a longitudinal research database of participants with suspected or diagnosed RASopathies. Participants will also complete surveys to be included in the research database (see "Research Database" section for details).


Secondary Outcome Measures :
  1. Release of Specimens and Clinical Data to Other Investigators for use in RASopathy Research [ Time Frame: 50 years ]
    Release of fresh or frozen specimens and clinical data to both CCHMC and external investigators. Applications for use of bio-specimen and/or data must be approved by the Repository Use Committee through the completion of a specimen request form. Among other data, the specimen request form will require information concerning: Principal Investigator, funding sources, a research synopsis, Institutional Review Board (IRB) approval of the research project, and details about the required samples. At the time a de-identified sample is requested, the requesting investigator may also request de-identified clinical data if needed.


Biospecimen Retention:   Samples With DNA
Specimens derived from blood, buccal cells, sputum, urine, bone marrow, tumor tissue and residual specimens, including but not limited to pleural fluid, ascetic fluid, chyle, skin, lung, lymphatic or renal tissue and/or bronchoalveolar lavage fluid, tissue specimens, and/or cells that are left over from clinical procedures from enrolled patients for research purposes only.

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The RASopathies are a group of developmental disorders caused by genetic changes in the genes that compose the Ras/mitogen activated protein kinase (MAPK) pathway. New RASopathies are being diagnosed frequently. This pathway is essential in the regulation of the cell cycle and the determination of cell function. Thus, appropriate function of this pathway is critical to normal development. Each syndrome in this group of disorders has unique phenotypic features, but there are many overlapping features including facial features, heart defects, cutaneous abnormalities, cognitive delays, and a predisposition to malignancies.
Criteria

Inclusion Criteria:

  • Patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies (e.g., Neurofibromatosis, Costello Syndrome, Noonan Syndrome). Diagnosis may be made clinically and/or confirmed through genetic testing.
  • Unaffected relatives of patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies.

Exclusion Criteria:

  • Individuals who do not have a suspected or definite diagnosis of a RASopathy.
  • Individuals who do not have a relative with a suspected or definite diagnosis of a RASopathy.
  • Patients who do not have the ability/capacity to undergo the informed consent process OR whose parent/legal guardian is unable to undergo the informed consent process.
Contacts and Locations
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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): NCT04395495


Contacts
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Contact: Lindsey Aschbacher-Smith, MS 513-803-0077 Lindsey.Aschbacher-Smith@cchmc.org
Contact: Laurie Bailey, MS 513-636-4507 Laurie.Bailey@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Lindsey Aschbacher-Smith, MS    513-803-0077    Lindsey.Aschbacher-Smith@cchmc.org   
Contact: Laurie Bailey, MS    (513) 636-4507    laurie.bailey@cchmc.org   
Principal Investigator: Carlos E Prada, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Kathryn N Weaver, MD Children's Hospital Medical Center, Cincinnati
  Study Documents (Full-Text)

Documents provided by Children's Hospital Medical Center, Cincinnati:
Study Protocol  [PDF] June 12, 2021
Informed Consent Form  [PDF] June 12, 2021

More Information
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Publications:

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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT04395495    
Other Study ID Numbers: 2016-7017
First Posted: May 20, 2020    Key Record Dates
Last Update Posted: March 11, 2022
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Noonan Syndrome
Costello Syndrome
LEOPARD Syndrome
Intellectual Disability
Lentigo
Syndrome
Disease
Pathologic Processes
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
 Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Neurobehavioral Manifestations
Neurologic Manifestations
Neurodevelopmental Disorders
Mental Disorders
Melanosis