Natural History Study of Patients With Neurofibromatosis Type I

NCT00924196 | Active Not Recruiting

• 2 other identifiers: 08007908-C-0079
• Study Type: observational
• Target: 259
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Neurofibromatosis Type 1 (NF1) is a genetic disorder in which patients are at increased risk of developing tumors (usually non-cancerous) of the central and peripheral nervous system. The disease affects essentially every organ system. The natural course of NFI over time is poorly understood. For most patients the only treatment option is surgery. A better understanding of NF1 may be helpful for the design of future treatment studies. Objectives: To evaluate people with NF1 over 10 years in order to better understand the natural history of the disease. To characterize the patient population and to examine how NFI affects patients quality of life and function. Eligibility: Children, adolescents, and adults with NF1. Design: Participants have a comprehensive baseline evaluation including genetic testing, tumor imaging, pain and quality-of-life assessments, and neuropsychological, motor and endocrine evaluations. Patients are monitored every 6 months to every 3 years, depending on their individual findings at the baseline study. Tests may include the following, as appropriate:

• Medical history, physical examination and blood tests.
• Whole body and face photography to monitor visible deformities.
• Neuropsychological testing, quality-of-life evaluations, motor function tests, endocrinologic evaluations, heart and lung function tests, hearing tests, bone density scans and other bone evaluations.
• MRI and PET scans to detect and assess plexiform neurofibromas (tumors that arise from nerves and can cause serious problems), paraspinal neurofibromas (tumors that arise from nerves around the spine and can cause problems by compressing the spinal cord), and malignant peripheral nerve sheath tumors (a type of cancer that arises from a peripheral nerve or involves the sheath covering the nerve).
• Eye exams, MRI scans and PET scans to evaluate optic pathway gliomas (tumors arising from the vision nerves or the brain areas for vision) and the chemicals within the tumor and brain.
• Eye exams and photographs to evaluate the development of Lisch nodules (non-cancerous tumors on the eye).
• Photographs of dermal neurofibromas (tumors of the skin), cafe-au-lait spots (dark or pigmented areas on the skin that are often the first signs of NF1) and other skin problems.
• Pain evaluations to monitor the different types of pain patients experience, causes of the pain, how often the pain occurs, effect of the pain on quality of life, and what pain medications and alternative treatments, such as acupuncture, are effective.

Conditions

Plexiform Neurofibroma; Optic Glioma; Neurofibroma; Neurofibromatosis Type 1; Malignant Peripheral Nerve Sheath Tumor

Keywords

Plexiform Neurofibroma; Optic Pathway Tumor; Neurofibroma; Malignant Peripheral Nerve Sheath Tumor; Volumetric MRI; Natural History; Neurofibromatosis Type 1; NF1; Optic Glioma

Outcome Measures

Primary Outcomes (1)

• To serve as an umbrella protocol for the ongoing NF1 clinical trials program to longitudinally characterize and analyze NF1 related tumor and non-tumor manifestations, and to develop a better understanding of the biology of NF1 related manifesta...

  Characterized features will be described and presented.

  throughout the study

Study Arms (3)

Biologic parents of children and adults with NFI

Biologic parents of children and adults with NFI will be evaluated at one time point, using a Neuropsychological Test Battery and QOL Assessment. Closed to enrollment

Children and adults with NFI

Children and adults with NFI whose tumor and non tumor related manifestations will be longitudinally evaluated. Closed to enrollment

Unaffected siblings of children and adults with NFI

Unaffected siblings of children and adults with NFI will be evaluated at one time point using a Neuropsychological Test Battery and QOL Assessment. Closed to enrollment

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with a confirmed clinical diagnosis of NF1 or a confirmed NF1 mutation; unaffected siblings and biologic parents of the individuals with NFI who enroll in the study.

You may qualify if:

• Age:
• Less than or equal to 35 years of age for new patients evaluated at NIH.
• No upper age limit for patients previously enrolled on clinical trials at NIH or for patients diagnosed with MPNST, or with clinical concern for MPNST, or with infrequent or unusual NF1 related manifestations.
• Diagnosis: Patients who are diagnosed with NF1 using the NIH Consensus Conference criteria or have a confirmed NF1 mutation with analysis performed in a CLIA-certified laboratory. NF1 mutation testing to confirm eligibility will not be performed on this protocol, but as part of a separate screening study. Histologic confirmation of NF1 related benign tumors is not necessary in the presence of consistent clinical and radiographic findings, but is required for individuals with MPNST who enroll on this study.
• For the clinical diagnosis of NF1 all study subjects must have at least two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):
• Six or more cafe-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects).
• Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma.
• Freckling in the axilla or groin.
• Optic glioma.
• Two or more Lisch nodules.
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex).
• A first-degree relative with NF1.
• Prior and current therapy: For NF1 related benign tumor manifestations there is no standard effective medical treatment, and surgery is the only standard treatment. Chemotherapy and radiation therapy are additional treatment options for malignant NF1 related tumors. For the purpose of this study, subjects who have not previously received medical or surgical treatment, patients, who have previously received medical or surgical treatment, and patients who are currently receiving medical treatment and/or radiation for a NF1 related manifestation will be eligible. Prior and current treatment for NF1 related manifestations will be recorded at trial entry and throughout the study.
• Performance Status: ECOG less than or equal to 3. Subjects who are wheelchair bound because of paralysis will be considered ambulatory when they are up in their wheelchair. Subjects have to be able to travel to the NIH for evaluations.
• Informed Consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions.

You may not qualify if:

• In the opinion of the investigator the patient is not able to return for follow-up visits or obtain required follow-up studies.
• In the opinion of the investigator the patient is not able to obtain an MRI scan.
• Individuals who are pregnant or breast feeding or who become pregnant while enrolled on this trial will not be excluded from participation, but will not undergo radiographic evaluations or MRI scans requested for research purposes, or other studies which might negatively impact on the pregnancy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (7)

• Ferner RE. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol. 2007 Apr;6(4):340-51. doi: 10.1016/S1474-4422(07)70075-3.

  PMID: 17362838 BACKGROUND

• Korf BR. Clinical features and pathobiology of neurofibromatosis 1. J Child Neurol. 2002 Aug;17(8):573-7; discussion 602-4, 646-51. doi: 10.1177/088307380201700806.

  PMID: 12403555 BACKGROUND

• Kim A, Gillespie A, Dombi E, Goodwin A, Goodspeed W, Fox E, Balis FM, Widemann BC. Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas. Neurology. 2009 Oct 20;73(16):1273-9. doi: 10.1212/WNL.0b013e3181bd1326.

  PMID: 19841379 BACKGROUND

• Al Ghriwati N, Little P, Martin S, Tamula MA, Widemann BC, Wolters PL. Parent-child discrepancies in reports of child psychosocial functioning in neurofibromatosis type 1. J Fam Psychol. 2025 Feb;39(1):99-106. doi: 10.1037/fam0001256. Epub 2024 Oct 17.

  PMID: 39418437 DERIVED

• Curry BP, Alvarez R, Widemann BC, Johnson M, Agarwal PK, Lehky T, Valera V, Chittiboina P. Robotic Nerve Sheath Tumor Resection With Intraoperative Neuromonitoring: Case Series and Systematic Review. Oper Neurosurg. 2022 Feb 1;22(2):44-50. doi: 10.1227/ONS.0000000000000051.

  PMID: 35007270 DERIVED

• Akshintala S, Baldwin A, Liewehr DJ, Goodwin A, Blakeley JO, Gross AM, Steinberg SM, Dombi E, Widemann BC. Longitudinal evaluation of peripheral nerve sheath tumors in neurofibromatosis type 1: growth analysis of plexiform neurofibromas and distinct nodular lesions. Neuro Oncol. 2020 Sep 29;22(9):1368-1378. doi: 10.1093/neuonc/noaa053.

  PMID: 32152628 DERIVED

• Dagalakis U, Lodish M, Dombi E, Sinaii N, Sabo J, Baldwin A, Steinberg SM, Stratakis CA, Widemann BC. Puberty and plexiform neurofibroma tumor growth in patients with neurofibromatosis type I. J Pediatr. 2014 Mar;164(3):620-4. doi: 10.1016/j.jpeds.2013.10.081. Epub 2013 Dec 8.

  PMID: 24321536 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibromatosis 1; Neurofibrosarcoma; Neurofibroma, Plexiform; Optic Nerve Glioma; Neurofibroma

Condition Hierarchy (Ancestors)

Neurofibromatoses; 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; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Neoplasms by Site; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: February 25, 2008
• Last Updated: May 1, 2026

Record last verified: 2025-08-21

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)