Natural History Study of Patients With Neurofibromatosis Type 2
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|ClinicalTrials.gov Identifier: NCT00598351|
Recruitment Status : Recruiting
First Posted : January 21, 2008
Last Update Posted : July 20, 2020
This study will examine over the long-term the progress of patients with neurofibromatosis Type 2 (NF2), a condition associated with tumors of the nerves, brain and spinal cord. It will study patients tumors to learn how fast they can grow and if certain factors might affect their growth. It will also examine the effects of the tumors on patients abilities to carry out activities of daily living.
People between 8 and 75 years of age with NF2 may be eligible for this study. Participants undergo the following procedures:
Initial evaluation, including hearing and balance testing, magnetic resonance imaging (MRI) scans of the brain/spine and right upper extremity, nverve conduction study and electromyography of the arms/legs, blood tests, questionnaires, and physical and neurological examinations.
MRI scans of the brain and spine every 12 months to follow the size and number of tumors.
Physical and neurological examinations, questionnaires and blood tests every 12 months.
Auditory tests every 12 months for hearing patients. These tests evaluate middle and inner ear function and the patient s ability to hear tones at different frequencies and to hear words at different volumes. The subject responds to tones and words that are delivered through earphones.
Vestibular testing if the patient experiences changes in balance or undergoes treatment for vestibular schwannoma (a tumor that develops on the hearing and balance nerves). These tests check the function of various components of the balance system (eyes, inner ear, or leg and body sensation and muscles). They include:
- Videoelectronystagmogram Tracks subjects eye movements while they follow moving red lights with their eyes.
- Vestibular evoked myogenic potential Assesses subjects neck muscle movements in response to noise.
- Posturography Determines which parts of the balance system the subject relies on most. Subjects stand on a platform and try to maintain their balance while changes are made to the platform and the environment.
- Rotary chair test Subjects eye movements are monitored as they follow red spots and strips of light with their eyes while seated in a rotary chair that turns side to side at several speeds.
Primary Outcome Measures :
1. To determine the natural history (clinical and radiographic) of nervous system tumors in NF2
Secondary Outcome Measures :
- To identify underlying causes, and patterns or progression of speech and swallowing problems in patients with NF2.
- To identify imaging biomarkers of hearing loss in patients with NF2.
- To identify the etiology of peripheral neuropathy in patients with NF2.
- To identify serum biomarkers of NF2 disease progression.
|Condition or disease|
With this prospective natural history study on neurofibromatosis type 2 (NF2) study, we hope to understand the factors leading to tumor progression and neurological disease burden in NF2.
A total of 269 participants, ages 8-75, with a clinical or genetic diagnosis of NF2 will participate in this study.
Study participants will be evaluated with a thorough physical and neurologic examination upon enrollment. This initial outpatient evaluation will include magnetic resonance imaging with contrast of brain and spine and blood collection for research use. Participants with measurable hearing will have audiology assessment performed during the initial visit. Participants with untreated vestibular schwannomas will have vestibular assessment performed during the initial visit. Genetic studies performed outside will be acceptable as confirmation of NF2 in enrolled patients. If needed to confirm NF2 with genetic studies, or for research purpose, whole genome/whole exome sequencing may be performed on blood obtained from subjects enrolled in this study. All participants will be evaluated by a speech language pathologist.
Subjects will be followed as outpatients for up to ten years, during which clinical, and radiologic evaluation will be performed annually. Auditory testing will be performed annually for participants with measurable hearing. Participants with initially untreated vestibular schwannomas will be followed annually with vestibular testing. Speech and swallowing reassessments will be repeated if worsening of speech or swallowing is reported. Blood will be collected at each visit for blood biomarker testing
We hope to understand the biologic basis for speech and swallowing dysfunction in patients with NF2. We will study and report the strength of association of MRI findings, clinical assessments cranial nerve deficits and speech/swallowing dysfunction. We hope to
identify imaging biomarkers of hearing loss in NF2. We will attempt to discover the mode of peripheral neuropathy in patients with NF2. Lastly, we will attempt to discover previously unknown serum biomarkers associated with high tumor burden in NF2.
|Study Type :||Observational|
|Estimated Enrollment :||269 participants|
|Official Title:||A Prospective Natural History Study of Patients With Neurofibromatosis Type 2 (NF2)|
|Actual Study Start Date :||March 21, 2008|
Patients must have the diagnosis of NF2 by established clinical criteria or genetic testing.
- To determine the natural history (clinical and radiographic) of nervous system tumors in NF2 [ Time Frame: annual for up to 10 years ]Clinical Variables (longitudinal: measured annually for each subject)a. Subjective speech and swallowing dysfunction (binary)b. Spinal cord function:Modified ASIA Motor Scalec. Ambulatory status:modified McCormick grading scaled. Overall function:Karnofsky Performance Statuse. NFTI-QOLf. Functional Independence Measure scale MRI Variables (longitudinal: measured annually for each subject):a. Tumor volume (continuous variable) for VS tumors, meningiomas, other schwannomas, ependymomas, and Total tumor burden (number and volume). Specific growth rates of tumors.b. FLAIR hyper-intensity MRI Variables (cross-sectional: measured at baseline and as needed for each subject):c. MRI of Right Upper and Lower Extremity Laboratory testing variables (longitudinal:measured annually for each subject):a. Audiometry Laboratory testing variables (cross-sectional:measured at baseline and as needed for each subject)b. EMG/NCV study valuesc. Vestibular testing Covariate variable:a. Ageb. Sex
- To identify the underlying causes, and patterns of progression of speech and swallowing problems in patients with NF2 [ Time Frame: Annual for up to 10 years ]Self-reported swallowing deficits (binary, yes vs no) based on the last Visit (cross-sectional data)
- To identify imaging biomarkers of hearing loss in patients with NF2 [ Time Frame: Annual for up to 10 years ]MRI Variables (longitudinal: measured annually for each subject):a. Tumor volume (continuous variable) for VS tumors, meningiomas, other schwannomas, ependymomas, and Total tumor burden(number and volume). Specific growth rates of tumors.b. FLAIR hyper-intensity MRI Variables (crosssectional: measured at baseline and as needed for each subject
- To identify the etiology of peripheral neuropathy in patients with NF2 [ Time Frame: Annual for up to 10 years ]MRI images of the Right upper extremity will be evaluated for the presence of peripheral nerve lesions at baseline. These imaging findings will be evaluated with respect to EMG/NCV results.
- To identify serum biomarkers of NF2 disease progression [ Time Frame: Annual for up to 10 years ]determination of serum biomarker status and suspected biologic markers of disease progression using quantitative immunoassay or newer proteomic approaches
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): NCT00598351
|Contact: Gretchen C Scott, R.N.||Not Listedfirstname.lastname@example.org|
|Contact: Prashant Chittiboina, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Prashant Chittiboina, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|