Developing Biomarkers of Plexiform Tumor Burden in Patients With Neurofibromatosis-Type 1

August 26, 2025 updated by: Carlos Prada, MD, Ann & Robert H Lurie Children's Hospital of Chicago

Developing Novel Biomarkers of Plexiform Neurofibroma Tumor Burden

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.

Study Overview

Status

Enrolling by invitation

Conditions

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

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients from the NF1 Clinical Program at Lurie Children's Hospital of Chicago

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine if glucosylceramide (GC) and lactosylceramide (LC) species levels correlate with tumor burden in patients with NF1
Time Frame: 1 year
The investigator and team will collect blood samples from individuals with NF1 stratified plexiform tumor (PNF) burden (none, small, intermediate, and large) versus age and sex matched healthy control.
1 year
Test if tumor burden correlates with GC and LC signature in individuals with NF1 who are undergoing clinical treatment with MEK inhibitors
Time Frame: 1 year
The investigator and team will enroll 20 individuals with NF1 and inoperable PNFs in treatment with MEK inhibitors to correlate biomarker with tumor burden changes with therapy.
1 year
Assemble a longitudinal cohort of individuals with NF1 with plexiform neurofibromas (n=100) for deep phenotyping and tumor burden response to MEK inhibitors
Time Frame: 1 year
Whole-body MRI at baseline and at time of annual visit (9-to-18-month intervals) will be used to deeply phenotype individuals based on tumor burden and tumor volume. Individuals will undergo plasma collection and clinical history assessment (medications, diet log, supplements, and anthropometric measurements) at each visit. For patients undergoing treatment with MEK inhibitors, a sample prior to treatment will be collected during this study.
1 year
Determine if glucosylceramide (GC) and lactosylceramide (LC) signature correlates with plexiform neurofibroma burden change in longitudinal cohort of 100 individuals with PNFs
Time Frame: 1 year
The investigator and team will test GC/LC levels using validated mass spectrometry target method for quantification of these biomarkers.
1 year
Tumor volumetric analysis will be performed to correlate with GC/LC monitoring biomarker signature
Time Frame: 1 year
GC/LC biomarker thresholds (cut-off) will be refined to evaluate predictive ability to identify individuals with large tumor burden. Tumor burden will be measured from whole-body MRI analysis with post-imaging processing software.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)
Children's Hospital Medical Center, Cincinnati

Investigators

  • Principal Investigator: Carlos Prada, MD, Ann & Robert H Lurie Children's Hospital of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2022

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

January 19, 2022

First Submitted That Met QC Criteria

February 3, 2022

First Posted (Actual)

February 14, 2022

Study Record Updates

Last Update Posted (Estimated)

September 2, 2025

Last Update Submitted That Met QC Criteria

August 26, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-4928
  • 7R61NS122094-02 (U.S. NIH Grant/Contract)
  • 4R33NS122094-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neurofibromatosis 1

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe