Aspirin for Acoustic Neuroma

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by D. Bradley Welling, MD, PhD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Massachusetts Eye and Ear Infirmary

Must not be taking: Aspirin

Disqualifiers: Severe asthma, Hydrocephalus, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing whether aspirin can slow tumor growth and improve hearing in patients aged 12+ with vestibular schwannomas. Aspirin's anti-inflammatory properties might help achieve these effects. Aspirin has been studied for its potential to protect against certain types of hearing loss and has shown some protective effects in previous studies.

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.

What data supports the idea that Aspirin for Acoustic Neuroma is an effective drug?

The available research shows mixed results regarding the effectiveness of aspirin for treating Acoustic Neuroma. Some studies suggest that aspirin might help reduce tumor growth, as one study found less tumor growth in aspirin users when using more accurate measurements. However, other studies found no significant effect of aspirin on tumor growth. Overall, the evidence is conflicting, and more research is needed to determine aspirin's effectiveness compared to other treatments. ^{1 2 3 4 5}

What safety data exists for aspirin treatment in acoustic neuroma?

Aspirin, also known as acetylsalicylic acid (ASA), has been associated with several side effects, particularly at high doses. Common adverse reactions include gastrointestinal disturbances like heartburn and nausea, central nervous system effects such as tinnitus and, less frequently, deafness. These effects are dose-dependent, with higher doses increasing the likelihood of adverse reactions. Ototoxicity, including hearing loss and tinnitus, is a known side effect of high-dose aspirin, but these effects are generally reversible. The safety profile of aspirin suggests that while it is commonly used, caution is needed at higher doses due to the potential for ototoxicity and other side effects. ^{6 7 8 9 10}

Is aspirin a promising drug for treating acoustic neuroma?

Aspirin shows potential in reducing tinnitus, a symptom associated with acoustic neuroma, by affecting certain auditory functions. It can temporarily reduce tinnitus in some cases, making it a promising option for symptom relief. ^{6 7 8 9 11}

Research Team

Konstantina Stankovic, MD, PhD

Principal Investigator

Stanford University

D. Bradley Welling, MD, PhD

Principal Investigator

Massachusetts Eye and Ear

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Aspirin (Nonsteroidal Anti-inflammatory Drug)
• Placebo (Other)

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.

Participant Groups

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 Canada, China for the following indications:

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+

CarolAnn Williams

Massachusetts Eye and Ear Infirmary

Chief Executive Officer

MBA from Harvard Business School

Aalok Agarwala

Massachusetts Eye and Ear Infirmary

Chief Medical Officer since 2019

MD from University of California, Los Angeles

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Aspirin does not prevent growth of vestibular schwannomas: A case-control study. [2019]

2. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of aspirin for sporadic vestibular schwannoma: a meta-analysis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Impact of Aspirin and Other NSAID Use on Volumetric and Linear Growth in Vestibular Schwannoma. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Correlation Between Aspirin Intake and Reduced Growth of Human Vestibular Schwannoma: Volumetric Analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Vestibular Schwannoma Growth With Aspirin and Other Nonsteroidal Anti-inflammatory Drugs. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Aspirin selectively augmented N-methyl-D-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid does not alter the mechanoelectrical transduction of mammalian outer hair cells in vitro]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Acute toxicity of aspirin in hospitalized medical patients. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Aspirin ototoxicity: a rare situation today]. [2013]

10. United States 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. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Indications for aspirin as a palliative for tinnitus caused by SOAEs: a case study. [2019]