Brief Title
Developing Biomarkers of Plexiform Tumor Burden in Patients With Neurofibromatosis-Type 1
Official Title
Developing Novel Biomarkers of Plexiform Neurofibroma Tumor Burden
Brief Summary
The purpose of this study is to identify tumor biomarkers in individuals with
Neurofibromatosis type 1 (NF1). Biomarkers are signals that the investigator can measure that
tell us about a process such as progress of a disease or treatment. Individuals with this
diagnosis are at an elevated risk of developing a type of tumor called a plexiform
neurofibroma. Currently, detecting the risk factors of these tumors in children is difficult
and requires whole body imaging. The NF1 team at Lurie Children's established a way of using
blood plasma in mice with neurofibromatosis type 1 to identify biomarkers that might signal
the presence of tumors in people with NF1.
This study is an effort to create biomarker profiles of patients with NF1 with known tumors.
The study team will utilize whole-body MRI and mass spectrometry (a method for identifying
unknown compounds and the properties of molecules). The ultimate goal of this study is to
better understand the tumor biomarkers in patients with NF1.
Detailed Description
Neurofibromatosis type 1 (NF1) is a common inherited human disorder, with a frequency of
approximately 1:2500 worldwide. A hallmark of NF1 is development of plexiform neurofibromas
(PNFs) in 30 to 50% of NF1 patients. Currently, there are no biomarkers of tumor burden and
whole-body magnetic resonance imaging (MRI) is expensive and limited to few centers. The
investigator established an unbiased pipeline to identify candidate biomarker signals of
tumor burden using plasma from neurofibroma-bearing DhhCre;Nf1fl/fl mice using untargeted
metabolomics. Our preliminary data show that glucosylceramide (GC) is the most significantly
deregulated compound in plasma from neurofibroma-bearing DhhCre;Nf1fl/fl mice. The
investigator developed a novel targeted mass spectrometry method to accurately quantify
multiple elevated GC and lactosylceramide (LC) species. In this proposal, the investigator
will combine the clinical infrastructure of the NF1 comprehensive program and advance imaging
at Ann & Robert H. Lurie Children's Hospital of Chicago with the mass spectrometry
capabilities at Cincinnati Children's Hospital Medical Center.
Taking advantage of our large, well-characterized, Lurie Children's NF1 population, the
investigator propose to perform analytical validation studies of candidate GC/LC biomarker
signature of tumor burden in plasma from NF1 patients with defined numbers of PNF (tumor
burden) by whole body MRI. The potential outcomes of our study are identification of
candidate biomarker of tumor burden that contribute to patient risk stratification, and
analytical validation of GC/LC biomarker signature (context of use). Collectively, this work
represents a synergistic approach for discovery and validation of biomarkers of tumor burden
in NF1.
Study Type
Observational [Patient Registry]
Primary Outcome
Determine if glucosylceramide (GC) and lactosylceramide (LC) species levels correlate with tumor burden in patients with NF1
Condition
Neurofibromatosis 1
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
200
Start Date
March 4, 2022
Completion Date
June 2026
Primary Completion Date
June 2024
Eligibility Criteria
Inclusion Criteria:
1. Individuals with known diagnosis of neurofibromatosis type 1 (NF1)
Exclusion Criteria:
1. Patient does not meet NF1 diagnostic criteria
2. Mosaic NF1 individuals
3. Pregnant at Screening
4. 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.
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Carlos Prada, MD, 312-227-4391, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05238909
Organization ID
2022-4928
Secondary IDs
1R61NS122094-01
Responsible Party
Principal Investigator
Study Sponsor
Ann & Robert H Lurie Children's Hospital of Chicago
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Study Sponsor
Carlos Prada, MD, Principal Investigator, Ann & Robert H Lurie Children's Hospital of Chicago
Verification Date
March 2022