Aspirin for Acoustic Neuroma

Recruiting at 6 trial locations

Overseen By Odeta Dyrmishi

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts Eye and Ear Infirmary

Must not be taking: Aspirin

Disqualifiers: Severe asthma, Hydrocephalus, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether aspirin can slow the growth of acoustic neuromas (a type of non-cancerous brain tumor) and improve or maintain hearing in affected individuals. Participants will receive either aspirin or a placebo (a pill without active medicine) to determine any differences in outcomes. Ideal participants are those diagnosed with vestibular schwannoma (a specific type of acoustic neuroma) and who can swallow tablets. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important medical advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have been using aspirin daily in the last two months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that aspirin is generally safe for use. Many individuals take it regularly to relieve pain or reduce swelling. In studies on vestibular schwannomas, non-cancerous brain tumors, aspirin appeared to slow tumor growth. Specifically, one study found that individuals who took aspirin were about half as likely to experience tumor growth compared to those who did not. This suggests that aspirin might help manage these tumors without causing serious side effects. However, like any medication, some individuals might experience mild side effects, such as an upset stomach or an increased risk of bleeding. These findings indicate that aspirin is relatively safe for most people when used as directed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acoustic neuroma, which usually involve surgery or radiation therapy, aspirin offers a non-invasive alternative. Researchers are excited about aspirin because it may reduce tumor growth by targeting inflammation, a mechanism that differs from the typical approaches. This could lead to a safer and more convenient option for patients, especially those who are not ideal candidates for surgery or prefer to avoid radiation.

What evidence suggests that aspirin might be an effective treatment for acoustic neuroma?

This trial will compare the effects of aspirin with a placebo in patients with acoustic neuromas. Studies have shown that aspirin might slow the growth of vestibular schwannomas, also known as acoustic neuromas. Research indicates that people who took aspirin experienced a lower chance of tumor growth, with their tumors growing at half the rate compared to those who didn't take aspirin. In animal studies, aspirin also slowed the growth of similar tumors. This suggests that aspirin could potentially help maintain or improve hearing by slowing tumor growth. While more research is needed, these findings offer hope that aspirin might be effective for this condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Konstantina Stankovic, MD, PhD

Principal Investigator

Stanford University

D. Bradley Welling, MD, PhD

Principal Investigator

Massachusetts Eye and Ear

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older with a type of benign brain tumor called vestibular schwannoma, which can affect hearing. Participants must be able to swallow tablets and give informed consent; children need parental consent as well. People using daily aspirin, those allergic to it, pregnant women, and patients with severe illnesses like asthma or conditions affecting MRI scans cannot join.

Inclusion Criteria

I am 12 years old or older.

I can swallow pills.

I have a tumor on my hearing and balance nerve, confirmed by imaging.

Exclusion Criteria

You are allergic to aspirin.

You cannot handle getting an MRI with contrast.

My child is under 18 and currently has a fever or flu-like symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants receive either 325 mg aspirin twice daily or a placebo until tumor progression

Up to 42 months

Open Label Follow Up

Participants who progress on placebo may receive unblinded aspirin and are followed until further progression or definitive treatment

Up to 42 months post-baseline

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Placebo

Trial Overview The study is testing if aspirin can slow down the growth of vestibular schwannomas and help maintain or improve hearing in affected patients. It's a phase II trial where participants are randomly assigned to receive either aspirin or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Aspirin Experimental Treatment 1 Intervention

Patients on the experimental arm will receive blinded aspirin. Pediatric subjects who weigh less than 110 lbs will take 81mg aspirin twice a day. All other subjects will take 325mg aspirin twice a day.

Group II: Placebo Placebo Group 1 Intervention

Patients on the placebo arm will receive blinded placebo and take it twice a day.

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary

Lead Sponsor

Trials

115

Recruited

15,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Acetylsalicylic acid (ASA) has been shown to effectively reduce pain during migraine attacks, with a significant decrease in trigeminal somatosensory evoked potentials observed in a study involving cats, indicating its analgesic effects.

The pain relief from ASA does not involve opioid receptors, as naloxone did not reverse its effects, suggesting that ASA works through different mechanisms, such as modulating neuronal activity and inhibiting neurogenic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous acetylsalicylic acid inhibits central trigeminal neurons in the dorsal horn of the upper cervical spinal cord in the cat. Kaube, H., Hoskin, KL., Goadsby, PJ.[2019]

Aspirin intake was not found to be associated with the stability of vestibular schwannomas (VS) after controlling for factors like age, sex, and tumor size, indicating that aspirin may not be effective in reducing tumor growth.

The only significant predictor of VS growth was tumor size at diagnosis, with 92% of patients being able to safely take aspirin, suggesting that most patients have low risk for complications from its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin does not prevent growth of vestibular schwannomas: A case-control study. MacKeith, S., Wasson, J., Baker, C., et al.[2019]

In a study of 347 patients with sporadic vestibular schwannoma (VS), those who took aspirin showed significantly less tumor growth compared to non-users, with an odds ratio of 0.32 indicating a strong inverse association.

The study also found that VS-induced hearing loss was more pronounced at higher frequencies, supporting previous findings of high-frequency sensorineural hearing loss in VS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation Between Aspirin Intake and Reduced Growth of Human Vestibular Schwannoma: Volumetric Analysis. Kandathil, CK., Cunnane, ME., McKenna, MJ., et al.[2021]

High doses of acetylsalicylic acid (ASS) can lead to tinnitus and hearing loss by competitively binding to the motor molecule prestin in outer hair cells, reducing their membrane capacitance by up to 42%.

The study indicates that while ASS affects the electromotility of outer hair cells, it does not alter the function of hair bundles, suggesting a specific mechanism of ototoxicity that may differ between mammals and non-mammalian species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid does not alter the mechanoelectrical transduction of mammalian outer hair cells in vitro]. Preyer, S., Meyer, J.[2018]

Aspirin effectively reduced tinnitus in a patient caused by spontaneous otoacoustic emissions (SOAEs), with the tinnitus becoming inaudible after administering 2.4 g of aspirin over two days.

The effect of aspirin was temporary, as both the tinnitus and SOAE returned 24 hours after the last dose, but no side effects were reported, indicating a potential safe palliative treatment for this specific case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indications for aspirin as a palliative for tinnitus caused by SOAEs: a case study. Penner, MJ., Coles, RR.[2019]

In a study of 564 patients with vestibular schwannoma (VS), aspirin use was not linked to tumor growth, indicating that it does not affect the size or growth rate of these tumors.

Similarly, the use of other non-aspirin NSAIDs and their COX-2 selectivity showed no significant impact on VS growth, suggesting that these medications do not influence the progression of vestibular schwannomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vestibular Schwannoma Growth With Aspirin and Other Nonsteroidal Anti-inflammatory Drugs. Hunter, JB., O'Connell, BP., Wanna, GB., et al.[2018]

In a study of 2,391 aspirin recipients, 5.1% experienced adverse reactions, with the most common being minor gastrointestinal issues like heartburn and nausea (2.1%).

Serious reactions were rare, with gastrointestinal bleeding occurring in 1.0% of patients, and deafness reported only at high doses, indicating that while aspirin can cause side effects, they are generally mild and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity of aspirin in hospitalized medical patients. Miller, RR., Jick, H.[2019]

A systematic review of four retrospective cohort studies found no significant difference in tumor growth between patients with vestibular schwannomas taking aspirin and those who were not, indicating that aspirin may not be effective in slowing tumor growth.

The analysis included various measures of tumor growth, and the results suggest that there is currently insufficient evidence to recommend aspirin therapy for patients with vestibular schwannomas, highlighting the need for high-quality randomized controlled trials to further investigate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of aspirin for sporadic vestibular schwannoma: a meta-analysis. Ignacio, KHD., Espiritu, AI., Diestro, JDB., et al.[2021]

Acute aspirin intoxication can lead to temporary hearing loss, tinnitus, and vertigo, occurring at doses of several grams, which is much higher than typical low daily doses.

The ototoxic effects of aspirin are reversible and are thought to be caused by the inhibition of prestin, a protein that affects the movement of outer hair cells in the inner ear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aspirin ototoxicity: a rare situation today]. Cuffel, C., Guyot, JP.[2013]

Aspirin selectively enhances NMDA receptor-mediated responses in type I spiral ganglion neurons, indicating it may interfere with glutamatergic neurotransmission in the cochlea.

The study found that aspirin had minimal impact on voltage-gated sodium and potassium currents, suggesting its primary action in the auditory system is through modulation of NMDA receptors rather than affecting basic neuronal excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin selectively augmented N-methyl-D-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice. Peng, BG., Chen, S., Lin, X.[2019]

A study involving 361 patients with vestibular schwannoma analyzed 1601 MRI studies and found that neither aspirin nor other NSAIDs significantly reduced the risk of tumor growth, with similar growth rates among users and non-users.

Regardless of the dosage (81 mg or 325 mg), aspirin did not show any protective effect against tumor growth, suggesting that the use of these medications may not be beneficial in managing vestibular schwannoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Aspirin and Other NSAID Use on Volumetric and Linear Growth in Vestibular Schwannoma. Marinelli, JP., Lees, KA., Tombers, NM., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03079999

Study of Aspirin in Patients With Vestibular Schwannoma In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11960480/

Why Consider Aspirin for the Treatment of Vestibular ... Treatment of patient‐mimicking NF2‐associated schwannomas in mice with moderate doses of aspirin resulted in decreased schwannoma progression in ...

3. withpower.com withpower.com/trial/phase-3-neurofibromatosis-2-5-2018-7cc94

Aspirin for Acoustic Neuroma This trial is testing whether aspirin can slow tumor growth and improve hearing in patients aged 12+ with vestibular schwannomas.

4. actaneurocomms.biomedcentral.com actaneurocomms.biomedcentral.com/articles/10.1186/s40478-019-0760-0

COX2 expression is associated with proliferation and tumor ... COX2 expression is associated with proliferation and tumor extension in vestibular schwannoma but is not influenced by acetylsalicylic acid intake.

5. researchgate.net researchgate.net/publication/259846572_Aspirin_Intake_Correlates_With_Halted_Growth_of_Sporadic_Vestibular_Schwannoma_In_Vivo

Aspirin Intake Correlates With Halted Growth of Sporadic ... A significant inverse association was found among aspirin users and sVS growth (odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.29-0.85), ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S193152441500002X

Nonsteroidal anti-inflammatory medications are cytostatic ... Changes in proliferation, cell death, and cell viability were analyzed in primary VS cultures treated with aspirin, sodium salicylate, or 5-aminosalicylic acid.