Enhancing Facial Nerve Function With Omega-3 After Resection of Vestibular Schwannoma

Study Overview
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Brief Summary
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The purpose of this research is to develop a therapeutic agent to help improve facial nerve outcomes and ultimately improve long-term quality-of-life following surgical resection of vestibular schwannomas. It is possible the therapeutic agent may impact tumor control rates as well, and this will also be studied. Using rigorous scientific methods, we will assess whether these factors are impacted by the treatment agent (Omega-3) versus placebo control (cellulose).

Detailed Description
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Vestibular schwannomas (VS) are common, often-benign intracranial neoplasms, however surgical resection carries high risk of causing neurologic impairments that may severely impact patient quality-of-life. The most morbid common postoperative deficit is facial weakness due to the close anatomic proximity of VS with the facial nerve, which is frequently stretched and attenuated by the tumor itself, and subject to additional mechanical stress during surgery. In addition to disfiguring cosmesis, facial weakness carries the secondary effects of abnormal speech, ocular morbidity from inadequate eye closure and corneal lubrication, and dysfunctional swallowing mechanics. Some patients may eventually recover partial facial nerve function; however, this is an unreliable process that proceeds slowly over months to years, if at all. At present, no pharmacologic avenue exists for promoting facial nerve neuroprotection or regeneration. Correspondingly, the development of a therapeutic agent to stimulate improved facial nerve outcomes would markedly enhance patient outcomes and quality-of-life. In the anterior skull base, loss of olfaction is a common sequela of following endoscopic surgical resection due to direct nerve manipulation, impacting approximately 25% of patients who undergo endoscopic endonasal tumor resection. In a recent randomized clinical trial, postoperative supplementation with omega-3 yielded a significant, sustained 1-2-point improvements on the University of Pennsylvania Smell Identification Test as assessed at six weeks, three months, and six months post-operatively. Although mechanistic understanding of the relationship between omega-3 supplementation and olfactory function preservation is incompletely understood, preliminary data support the hypothesis of direct neural regeneration and/or neuro-protective effects through anti-demyelination effects. More specifically, polyunsaturated fatty acids have been shown to modulate neural plasticity and provide a protective role in maintaining functional neuronal cell membranes thought to be critical for maintaining nerve connectivity and function. It is also possible that omega-3, a known anti-inflammatory agent through reducing local IL-6, TNF, NFkB, impacts the innate immune system to mitigate demyelination and other destructive post-treatment inflammatory injuries to cranial nerves and surrounding support cells. Given the highly interrelated mechanisms-of-injury resulting in olfactory deficit after anterior skull base surgery and facial weakness after VS resection, application of omega-3 fatty acids may provide similar benefits with respect to facial nerve protection and/or rehabilitation. As a fascinating aside, new pre-clinic animal model evidence also suggests that omega-3 fatty acid supplementation may result in delayed progression in a neuroblastoma xenograft model. These effects are attributed to anti-inflammatory and anti-angiogenic effects via anti-VEGF and other anti-proliferative growth factors; factors also implicated in VS pathophysiology, suggesting that omega-3 may also impact early tumor control as well. We hypothesize that post-operative omega-3 supplementation will improve facial nerve function following resection of vestibular schwannomas and enhance early tumor control rates.

Official Title
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Enhancing Facial Nerve Neuroprotection and Regeneration Through Omega-3 Supplementation Following Vestibular Schwannoma Resection

Conditions
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Vestibular Schwannoma

Intervention / Treatment
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* Dietary Supplement: Omega-3
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: VS on final pathology report Surgical intervention (RS, MF, TL, other) Primary and revision cases included, including prior radiation Exclusion Criteria: History of liver disease or abnormal liver function tests Diabetic patients with specific contraindication to omega-3 supplementation History of bleeding disorder, or recommended use of anticoagulation (not including anti-platelets or NSAIDs) during the treatment period Neurofibromatosis 1 or 2, or schwanomatosis disorders Non-VS pathology Patients already taking fish oil/omega-3 supplementation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blinded, placebo-controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omega-3 Group<br>Subjects will receive omega-3 supplementation (Nature's Bounty Fish Oil 1400 mg, containing 980 mg Omega-3 per capsule), to begin taking 3 days prior to surgical resection of their vestibular schwannoma. Subjects will continue to take the omega-3 supplementation for 6 weeks post-operatively. | Dietary Supplement: Omega-3<br>* One capsule orally twice daily beginning 3 days prior to clinical care surgical intervention and continuing 6 weeks post-operative<br>|
| Placebo Comparator: Placebo Group<br>Subjects will receive a placebo to begin taking 3 days prior to clinical care of surgical resection of vestibular schwannoma. Subjects will continue to take the placebo for 6 weeks post-operatively. | Dietary Supplement: Placebo<br>* One cellulose capsule orally twice daily beginning 3 days prior to clinical care surgical intervention and continuing 6 weeks post-operative<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in facial nerve function | Subjects will receive independent examination by at least three expert clinical assessors using the standardized, and clinically validated, House-Brackmann facial function score to characterize the severity of facial paralysis. Score is determined by measurements (in cm) of subjects movements of facial reference points on a scale of 0-8 which translate to grading system of grade I (normal) - Grade VI (no facial motion) | Baseline, 3 and 12 months post-operative | 
| Tumor Control | Number of subjects to have tumor recurrence or progression of vestibular schwannoma as assessed by post-operative radiography (MRI) imaging | 12 months post-operative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Facial nerve outcomes, Vestibular schwannoma resection, Acoustic neuroma, Omega-3, Nerve regeneration, Neuroprotection