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Natural History Study of Patients With Neurofibromatosis Type 2

Recruiting
Conditions
Neurofibromatosis
Registration Number
NCT00598351
Lead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Brief Summary

Objective

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.

Study Population

A total of 269 participants, ages 8-75, with a clinical or genetic diagnosis of NF2 will participate in this study.

Design

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

Outcome measures

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.

Detailed Description

Objective

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.

Study Population

A total of 269 participants, ages 8-75, with a clinical or genetic diagnosis of NF2 will participate in this study.

Design

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

Outcome measures

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
269
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To determine the natural history (clinical and radiographic) of nervous system tumors in NF2annual 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

Secondary Outcome Measures
NameTimeMethod
To identify the underlying causes, and patterns of progression of speech and swallowing problems in patients with NF2Annual 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 NF2Annual 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 NF2Annual 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 progressionAnnual for up to 10 years

determination of serum biomarker status and suspected biologic markers of disease progression using quantitative immunoassay or newer proteomic approaches

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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