Vagus Nerve Stimulation for Brain Aneurysm Bleeding

(STORM Trial)

Overseen By Austin R Birmingham, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Carotid disease, Heart blocks, SVT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: Up to 10 days

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device called gammaCore, which uses non-invasive vagus nerve stimulation to treat brain aneurysm bleeding. The goal is to determine if it can safely reduce complications such as aneurysm ruptures and seizures, improve recovery, and increase survival rates. Individuals who have experienced a brain aneurysm rupture treated by a doctor within the last 72 hours may be suitable for this trial. Participants will use the device to assess its effectiveness in improving their condition in a critical care setting. As an unphased trial, this study provides participants the chance to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using any electrostimulation devices like a pacemaker, you cannot participate.

What prior data suggests that this device is safe for treating brain aneurysm bleeding?

Research has shown that the gammaCore device, which uses non-invasive vagus nerve stimulation (nVNS), is designed as a low-risk treatment option. Studies have examined its safety and effectiveness, finding that it typically provides mild electrical stimulation, which most patients tolerate well.

However, the safety and effectiveness of gammaCore for conditions like chronic cluster headaches remain under investigation. While some safety information is available, further studies are needed to fully understand its safety for new uses, such as treating aneurysmal subarachnoid hemorrhage (SAH) in this trial.

In summary, gammaCore appears to be a low-risk option, but its safety for specific new uses is still being studied. Participants should consider this when deciding whether to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for brain aneurysm bleeding, which often involve surgical interventions or endovascular procedures, gammaCore is a non-invasive device that stimulates the cervical branch of the vagus nerve. This unique approach taps into the body's natural mechanisms to potentially reduce bleeding by modulating nerve activity. Researchers are excited about gammaCore because it offers a less invasive option that could be safer and more accessible for patients who are not ideal candidates for surgery. Additionally, this method of nerve stimulation could lead to faster recovery times and fewer complications compared to traditional treatments.

What evidence suggests that gammaCore is effective for aneurysmal subarachnoid hemorrhage?

Research has shown that the gammaCore device for non-invasive vagus nerve stimulation (nVNS), which participants in this trial will receive, can help manage issues related to brain aneurysms. Studies have found that nVNS can lessen headache pain in people with subarachnoid hemorrhage, a type of brain bleeding. It also reduces the need for pain medications, like opioids, by managing pain more effectively. Early evidence suggests it might help lower the risk of an aneurysm bursting and reduce the severity of bleeding. Overall, nVNS appears promising in aiding recovery and improving outcomes for those with complications from brain aneurysms. ^{6 7 8 9 10}

Who Is on the Research Team?

Aman B Patel, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with a recent aneurysmal subarachnoid hemorrhage, who are conscious (mGCS score ≥ 10) and can start treatment within 72 hours of the rupture. It's not for those with neck surgeries, metal implants in the neck, heart rhythm problems, or using other electrostimulation devices.

Inclusion Criteria

I will start nVNS treatment within 3 days after my aneurysm is suspected to have burst.

I am of childbearing age and have a negative pregnancy test.

I was mostly awake and able to respond after a suspected brain bleed.

Exclusion Criteria

My aneurysm has not been treated surgically or through a catheter.

I have had carotid artery disease or surgery on my carotid artery.

I have a history of serious heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Within 72 hours of aneurysm rupture

Treatment

Participants receive non-invasive vagus nerve stimulation (nVNS) using the gammaCore device, 3 times daily for up to 10 days or until discharge

Up to 10 days

Continuous monitoring in NeuroICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at 10 days or discharge and 90 days post-rupture

90 days

Assessments at 10 days or discharge and 90 days post-rupture

What Are the Treatments Tested in This Trial?

Interventions

• gammaCore

Trial Overview The study tests gammaCore, a non-invasive vagus nerve stimulator, on patients with brain aneurysm bleeding to see if it lowers rupture rates, seizures, bleeding severity and improves survival. All 25 participants will receive this active treatment.

How Is the Trial Designed?

Group I: Treatment group Experimental Treatment 1 Intervention

The gammaCore device supplies non-invasive stimulation to the cervical branch of the vagus nerve.

gammaCore is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as gammaCore for:

• Acute treatment of episodic cluster headache
• Acute treatment of migraine
• Preventive treatment of cluster headache
• Preventive treatment of migraine
• Abortive and preventive treatment of hemicrania continua and paroxysmal hemicrania

Approved in European Union as gammaCore for:

• Cluster headache

Approved in United Kingdom as gammaCore for:

• Cluster headache

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

ElectroCore INC

Industry Sponsor

Trials

31

Recruited

2,200+

Published Research Related to This Trial

Cervical vagus nerve stimulation (VNS) can potentially treat various disorders, and this study developed models to estimate the engagement of different nerve fiber types (A, B, and C fibers) based on physiological responses like EMG, heart rate, and breathing intervals in anesthetized rats.

The findings suggest that specific physiological markers correlate with the activation of different fiber types, which could allow for noninvasive monitoring of VNS therapy in humans, enhancing the precision of treatment calibration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. Chang, YC., Cracchiolo, M., Ahmed, U., et al.[2021]

In a study of 11 patients with partial epilepsy, vagus nerve stimulation (VNS) was found to significantly alter regional cerebral blood flow (rCBF), particularly in the thalamus, which correlated with changes in seizure frequency.

Increased blood flow in the right and left thalami was associated with a decrease in seizure frequency, suggesting that thalamic activity may play a key role in the antiseizure effects of VNS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Henry, TR., Votaw, JR., Pennell, PB., et al.[2019]

In a study involving 248 participants with episodic migraine, noninvasive vagus nerve stimulation (nVNS) was found to be significantly more effective than a sham treatment for achieving pain freedom at 30 and 60 minutes after treatment.

nVNS was safe, well-tolerated, and provided effective pain relief, demonstrating a 13.2% absolute increase in the likelihood of being pain-free 2 hours post-treatment, making it a practical option for acute migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. Tassorelli, C., Grazzi, L., de Tommaso, M., et al.[2022]

Noninvasive vagus nerve stimulation (nVNS) using the GammaCore® device is effective for aborting migraine attacks, but its effect size is modest and not superior to other noninvasive methods or oral triptans.

nVNS has an excellent safety and tolerance profile, making it a favorable option for migraine treatment, although its preventive effects are not significantly better than sham stimulation, except possibly in patients who consistently adhere to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on noninvasive neuromodulation for migraine treatment-Vagus nerve stimulation. Schoenen, J., Ambrosini, A.[2021]

In a study involving 10 patients with partial epilepsy, vagus nerve stimulation (VNS) showed immediate effects on cerebral blood flow (CBF) that changed over a 3-month period, with significant decreases in CBF in certain brain regions during immediate stimulation but not during prolonged stimulation.

Despite the decline in immediate CBF changes, patients experienced a 25% reduction in seizure frequency over the same 3 months, suggesting that persistent CBF changes in subcortical regions may contribute to the antiseizure effects of VNS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. prolonged effects at high and low levels of stimulation. Henry, TR., Bakay, RA., Pennell, PB., et al.[2016]

In the PRESTO study, patients using non-invasive vagus nerve stimulation (nVNS) experienced a significant reduction in pain intensity compared to those receiving a sham treatment, with 46.8% reporting a decrease of at least 1 point in pain intensity at 120 minutes after treatment.

nVNS also reduced the need for rescue medication, with 59.3% of patients not requiring it after their first attack, compared to 41.9% in the sham group, highlighting its potential to minimize reliance on additional medications and their side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial. Grazzi, L., Tassorelli, C., de Tommaso, M., et al.[2023]

The ADNS-300 system for vagus nerve stimulation (VNS) was successfully implanted in all three patients, demonstrating its feasibility for therapeutic use and recording of nerve activity.

Two out of three patients experienced a significant reduction in seizure frequency (43% and 40%), indicating that the ADNS-300 system may effectively reduce seizures in refractory epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: pilot trial at Ghent University Hospital. El Tahry, R., Raedt, R., Mollet, L., et al.[2012]

The gammaCore device, a non-invasive vagus nerve stimulation (nVNS) system, has been FDA-cleared for the acute treatment of pain in patients with episodic cluster headaches, showing its efficacy in managing primary headache disorders.

Clinical studies indicate that nVNS effectively stimulates the same vagus nerve fibers as the traditional implanted vagus nerve stimulation (iVNS), suggesting a similar mechanism of action for headache relief without the associated risks of surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of action of non-invasive cervical vagus nerve stimulation for the treatment of primary headaches. Simon, B., Blake, J.[2018]

Non-invasive vagus nerve stimulation (nVNS) using gammaCore® has been shown to be a safe and effective treatment for acute migraines in adolescents, with 46.8% of migraine attacks successfully treated without the need for rescue medication.

The study reported no device-related adverse events, highlighting nVNS as a well-tolerated option for young patients suffering from migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive vagus nerve stimulation (nVNS) as symptomatic treatment of migraine in young patients: a preliminary safety study. Grazzi, L., Egeo, G., Liebler, E., et al.[2022]

Vagus nerve stimulation (VNS) is an effective therapy for adults and adolescents (12 years and older) with partial onset seizures that do not respond to traditional antiepileptic medications, with over 50,000 patients having received the treatment worldwide.

In addition to epilepsy, VNS is also approved for treatment-resistant depression and shows potential for treating other medical conditions, highlighting its versatility as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: a proven therapy for treatment of epilepsy strives to improve efficacy and expand applications. Terry, R.[2020]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05103566/safety-feasibility-and-efficacy-of-non-invasive-vagus-nerve-stimulation-nvns-in-the-treatment-of-aneurysmal-subarachnoid-hemorrhage

Safety, Feasibility, and Efficacy of Non-invasive Vagus ... The primary efficacy outcomes are reduced aneurysm rupture rate, reduced seizure and seizure-spectrum activity, minimized hemorrhage grades, and ...

2. investor.electrocore.com investor.electrocore.com/news-releases/news-release-details/data-highlighting-non-invasive-vagus-nerve-stimulation-nvns

Data Highlighting Non-Invasive Vagus Nerve Stimulation ... Our data suggests that nVNS is safe and effective in reducing pain and potentially the use of other acute pain medications, including opioids in the immediate ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24000627

Noninvasive vagus nerve stimulation in spontaneous ... Moreover, this is the first randomized study showing that nVNS is associated with a reduction in headache intensity in patients with subarachnoid hemorrhage.

4. clinicaltrial.be clinicaltrial.be/en/details/37379?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Safety, Feasibility, and Efficacy of Non-invasive Vagus N... The primary objective is to examine the safety, feasibility, and possible efficacy of nVNS as a treatment after aneurysmal subarachnoid ...

5. ctv.veeva.com ctv.veeva.com/study/safety-and-efficacy-of-non-invasive-vagus-nerve-stimulation-in-the-treatment-of-headache-in-subarach

Safety and Efficacy of Non-invasive Vagus Nerve Stimulation ... The primary objective of this study is to examine the safety and effectiveness of nVNS as a treatment for headache in subarachnoid hemorrhage ( ...

6. gammacore.com gammacore.com/about-gammacore/important-safety-information/

Important Safety and Performance Information See this page for important safety information on gammaCore non-invasive vagus nerve stimulator (nVNS).

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/reviews/DEN150048.pdf

De Novo Summary (DEN150048) Page 1 of 22 gammaCore ... The safety and effectiveness of the gammaCore Non-invasive Vagus Nerve Stimulator has not been established in the acute treatment of chronic cluster headache. B ...

8. gammacore.com gammacore.com/wp-content/uploads/2022/10/gammaCore-Sapphire-SLC-IFU.pdf

Instructions for Use for gammaCore SapphireTM SLC The safety and effectiveness of this device is based on a comparison of its low risks and probable benefit to health. gammaCore™ provides a mild electrical ...

9. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf19/K191830.pdf

March 26, 2020 Electrocore, Inc. Mike Romaniw VP, Quality ... The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the ...

10. electrocore.com electrocore.com/wp-content/uploads/2018/12/64000-00123-REV-2-Final_v2.pdf

Instructions for Use for gammaCore Sapphire™ gammaCore SapphireTM (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck.