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

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

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).

Study Overview

• Status: Terminated
• Conditions: Vestibular Schwannoma
• Intervention / Treatment: Dietary supplement: Omega-3; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omega-3 Group; 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; One capsule orally twice daily beginning 3 days prior to clinical care surgical intervention and continuing 6 weeks post-operative
Placebo Comparator: Placebo Group; 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; One cellulose capsule orally twice daily beginning 3 days prior to clinical care surgical intervention and continuing 6 weeks post-operative

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael Link, MD, Mayo Clinic; Study Director: Lucas P Carlstrom, MD, PhD, Mayo Clinic; Study Chair: Matthew L Carlson, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): August 2, 2023
• Study Completion (Actual): August 2, 2023

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Neuroprotection; Omega-3; Facial nerve outcomes; Vestibular schwannoma resection; Acoustic neuroma; Nerve regeneration
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Otorhinolaryngologic Neoplasms; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ear Diseases; Nervous System Neoplasms; Cranial Nerve Diseases; Neuroendocrine Tumors; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Neoplasms; Neuroma; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neurilemmoma; Neuroma, Acoustic
• Other Study ID Numbers: 21-007120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: May be available on specific requests for collaboration.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes