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

Trial Summary

What is the purpose of this trial?

This is a single-site, single-arm, open-label pilot study assessing the safety, feasibility, and efficacy of non-invasive vagus nerve stimulation (nVNS), gammaCore, for the acute treatment of aneurysmal subarachnoid hemorrhage (SAH) subjects in a neurocritical care setting. 25 patients will be enrolled, all treated with an active device. The primary efficacy outcomes are reduced aneurysm rupture rate, reduced seizure and seizure-spectrum activity, minimized hemorrhage grades, and increased survival.

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.

Is non-invasive vagus nerve stimulation (nVNS) safe for humans?

Non-invasive vagus nerve stimulation (nVNS), used in devices like gammaCore, has been shown to be safe and well-tolerated in humans, with a favorable safety profile and no significant device-related adverse events reported in studies for conditions like migraines. ^{1 2 3 4 5}

How is the treatment gammaCore for brain aneurysm bleeding different from other treatments?

GammaCore is unique because it uses non-invasive vagus nerve stimulation (VNS) to potentially alter blood flow in the brain, which is different from traditional treatments that might involve surgery or medication. This approach is novel as it leverages a device to stimulate the vagus nerve externally, which has been used in other conditions like epilepsy and depression, but is now being explored for brain aneurysm bleeding. ^{6 7 8 9 10}

Research Team

Aman B Patel, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

You have screws, metals, or devices in your neck.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Mechanism of action of non-invasive cervical vagus nerve stimulation for the treatment of primary headaches. [2018]

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

Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Update on noninvasive neuromodulation for migraine treatment-Vagus nerve stimulation. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Non-invasive vagus nerve stimulation (nVNS) as symptomatic treatment of migraine in young patients: a preliminary safety study. [2022]

5. England 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. [2023]

6. United States 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. [2016]

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

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. [2021]

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

Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. [2019]

9. Netherlands 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. [2012]

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

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