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
Trial record 1 of 1 for:    Frameshift Peptides of Children with Neurofibromatosis Type 1
Previous Study | Return to List | Next Study

Frameshift Peptides of Children With NF1

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: NCT04212351
Recruitment Status : Recruiting
First Posted : December 27, 2019
Last Update Posted : August 4, 2020
Sponsor:
Collaborators:
University of Texas Southwestern Medical Center
Arizona State University
Information provided by (Responsible Party):
Roger Packer, Children's National Research Institute

Brief Summary:
The objective of this study is to determine if children and young adults with Neurofibromatosis Type 1 (NF1) and either Low Grade Gliomas (LGGs) or Plexiform Neurofibromas (PNs) have a specific frameshift peptide protein profile and whether a disease specific vaccine created to address these frameshift mutations and variants can be developed. Three study populations will be analyzed; patients with NF1 and active LGGs, NF1 and active PNs, and NF1 and no evidence of active LGGs or PNs. Participation involves a onetime blood draw.

Condition or disease Intervention/treatment
Neurofibromatosis Type 1 Genetic: Frameshift Array blood sample test

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Frameshift Peptides of Children With Neurofibromatosis Type 1 (NF1) and Either Low-Grade Gliomas or Plexiform Neurofibromas
Actual Study Start Date : April 11, 2019
Estimated Primary Completion Date : April 11, 2021
Estimated Study Completion Date : April 11, 2022


Group/Cohort Intervention/treatment
Patients with NF1 and active LGGs
Patients with Neurofibromatosis Type 1 with clinical or radiographic evidence of low grade glioma but no clinical or radiographic evidence of plexiform neurofibroma.
Genetic: Frameshift Array blood sample test
Patient blood test samples will be collected and evaluated for frameshift peptide mutations.

Patients with NF1 and active PNs
Patients with Neurofibromatosis Type 1 with clinical or radiographic evidence of plexiform neurofibroma but no clinical or radiographic evidence of low grade glioma.
Genetic: Frameshift Array blood sample test
Patient blood test samples will be collected and evaluated for frameshift peptide mutations.

Patients with NF1 with no active LGGs or PNs
Patients with Neurofibromatosis Type 1 with no clinical or radiographic evidence of both active plexiform neurofibroma and active low grade glioma.
Genetic: Frameshift Array blood sample test
Patient blood test samples will be collected and evaluated for frameshift peptide mutations.




Primary Outcome Measures :
  1. Measure mean florescent intensity of serum/plasma samples for each cohort by assaying the study samples on frameshift peptide arrays consisting of peptides representing the ~220,000 frameshifts tumors can make in RNA processing. [ Time Frame: 2 years ]
    All samples will be assayed on the FSP arrays consisting of peptides representing the frameshifts tumors can make in RNA processing. The amount of IgG bound to each feature will be determined as florescent intensity generated by bound secondary antibody. The mean intensity across the 20 subjects for each peptide for each of the 3 groups will be determined. All peptides in the NF1+LGG group with mean intensities greater than 3 SD higher than the mean of the NF1-LGG/PN group will be determined. Those that meet this criterion in more than 3 of the 20 samples will be chosen. The 20 peptides with the highest prevalence across the 20 samples of NF1+LGG will be chosen for the vaccine. If two peptides have the same prevalence, the one with the highest average florescence will be chosen. The same procedure will be applied to determine the 20 peptide components for the NF1+PN vaccine.

  2. Use a feature counting method to establish a mean distinguishable frameshift peptide protein profile for early detection of tumors in patients with NF1. [ Time Frame: 2 years ]
    The same data as generated in Outcome 1 will be analyzed for the ability to distinguish NF1+LGG and NF1+PN samples from the NF1-LGG/PN samples. Since the antibody reactions to frameshift peptides are stochastic, a feature counting method is employed. A mean is established for each of the NF1-LGG/PN peptides. Any peptide in the NF1+LGG and NF1+PN samples that scores 3 SD higher than NF1-LGG/PN mean is scored as a positive. The total number of positives in the NF1+LGG and NF1+PN pool will be compared to that in the NF1-LGG/PN set. The number of samples that are distinguished by these counts will determine a first pass accuracy estimate of this diagnostic approach as a preamble to an expanded study.

  3. Use a feature counting method to establish a mean distinguishable frameshift peptide protein profile for patient who develop LGGs versus patients who develop PNs. [ Time Frame: 2 years ]
    The same array data generated in Outcome 1 will be used. The feature counting method used in Outcome 2 will be used to compare the NF1+LGG features to the NF1+PN features. The investigators will determine if there are a set of features that can distinguish the 20 NF1+LGG from the 20 NF1+PN samples. The number of NF1+LGG and NF1+PN samples that can be distinguished will provide a first estimate of accuracy and whether an expanded study is merited.


Secondary Outcome Measures :
  1. Correlate age, gender, family history of NF, disease state (stable, progressive, or improving), and disease history with frameshift peptide profiles, in children and young adults with NF1 and LGGs or PNs. [ Time Frame: 2 years ]
    Correlate age, gender, family history of NF, disease state (stable, progressive, or improving), and disease history with frameshift peptide profiles, in children and young adults with NF1 and LGGs or PNs.


Biospecimen Retention:   Samples With DNA
A frameshift peptide profile will be determined from patient blood samples


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:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
There will be a total of 60 patients enrolled in the study. Cohort 1 will consist of 20 subjects with NF1 and active LGG. Cohort 2 will consist of 20 subjects with NF1 and active PN. Cohort 3 will consist of 20 subjects with NF1 and no active LGG or active PN.
Criteria

Inclusion Criteria:

  1. Subjects must be between 1 day and 30 years of age, inclusive
  2. Subjects must either meet clinical criteria for NF1 or have molecular genetic germ line evidence of NF1
  3. Subject is able to have his/her blood sample drawn within a reasonable period of time after signing consent
  4. Subjects must either have:

    1. Active* LGGs, no active PNs (Cohort 1)
    2. Active* PNs, no active LGGs (Cohort 2)
    3. No active* LGGs or PNs (Cohort 3) *Active is defined as any LGG or PN that has shown growth (determined by MRI) in the past 12 months or is causing ongoing symptomatic visual, neurologic, or organ dysfunction or disfigurement as determined by the site investigator.

Exclusion Criteria:

1. Patients with NF1 with evidence of both LGG and PN


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): NCT04212351


Contacts
Layout table for location contacts
Contact: Bergen I. Kassoff, BA 2024764481 bkassoff@childrensnational.org
Contact: Roger J. Packer, MD 2024765973 RPacker@childrensnational.org

Locations
Layout table for location information
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Bergen I. Kassoff, BA    202-476-4481    bkassoff@childrensnational.org   
Principal Investigator: Roger J. Packer, MD         
Sub-Investigator: Miriam Bornhorst, MD         
United States, Texas
The University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9020
Contact: Laura Klesse, MD       Laura.Klesse@UTSouthwestern.edu   
Contact: Brittany Glass-Thomas    214-456-6439    Brittany.Glass-Thomas@childrens.com   
Principal Investigator: Laura Klesse, MD         
Sponsors and Collaborators
Children's National Research Institute
University of Texas Southwestern Medical Center
Arizona State University
Investigators
Layout table for investigator information
Principal Investigator: Roger J. Packer, MD Children's National Research Institute
Layout table for additonal information
Responsible Party: Roger Packer, Senior Vice President of Neurology and Behavorial Medicine, Children's National Research Institute
ClinicalTrials.gov Identifier: NCT04212351    
Other Study ID Numbers: Pro00011544
First Posted: December 27, 2019    Key Record Dates
Last Update Posted: August 4, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to make individual participant data available to other researchers outside of Children's National Medical Center.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Neoplasms by Histologic Type
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
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