Noninvasive Vagus Nerve Stimulation for Parkinson Disease Shows Safety, Efficacy

Serum tumor necrosis factor and glutathione levels decreased, and brain-derived neurotrophic factor levels increased significantly after treatment with electroCore’s gammaCore nVNS device.

Results from a randomized, double-blind, sham-controlled crossover trial using electroCore’s noninvasive vagus nerve stimulation (nVNS; gammaCore) device showed significant improvements in patients with Parkinson disease (PD) on key gait parameters, including walking speed, stance time, and step length compared to sham treatment.1,2

A total of 36 patients with associated freezing of gait were recruited for the study, of whom 17 were randomized to nVNS and 19 to sham stimulation. In the active nVNS group, velocity increased by 16% (P = .018), step length increased by 11% (P = .021) and step time decreased by 16% (P = .003), whereas the changes in velocity (2.3%; P = 1.0), step length (1%; P = 1.0) and step time (1.7%; P = .0708) were not significant in the sham group.

"We are pleased to have successfully completed the first randomized, double-blind sham-controlled trial to demonstrate the efficacy of cervical nVNS as an adjunctive therapy in PD,” Lead investigator Hrishikesh Kumar, MD, MBBS, director, Research, and vice chairman, Institute of Neursciences Kolkata, said in a statement.1 “Improvements in motor function and gait after 1 month of treatment with nVNS were significant. Our results clearly support additional work to further understand the potential for nVNS in this indication.”

The intervention was delivered at 3 pre-specific times every day: (1) within 1 hour of awakening; (2) 6 to 8 hours after the first treatment; and (3) 6 to 8 hours after the second treatment. In addition to improvements in motor and nonmotor symptoms of PD, patients reportedly were satisfied with the treatment and the majority were able to self-administer nVNS.

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Treatment with nVNS significantly reduced tumor necrosis factor alpha (TNF-a) levels (P <.05) and increased concentrations of reduced glutathione (P <.05), both of which are markers of inflammation in patients with PD. Unified Parkinson’s Disease Rating Scale (UPDRS) II and III scores, along with falls efficacy scale score and freezing of gait questionnaire score all improved significantly in both groups.

A small subset containing patients who experienced freezing of gait episodes while gait assessments were performed had the average duration of freezing episodes reduced from 21 seconds (±47) to 15 seconds (±37) with treatment of nVNS (P = .042). In comparison, no significant change was observed in the sham-treated group, which changed from 27 seconds (±67) to 72 seconds (±268)(P = .575). Notably, the average difference in freezing duration did not constitute a clinically meaningful change in either group.2

Reductions of 26.3% (P = .001) and 21% (P = .001) for total freezing of gait questionnaire scores were observed in the sham and nVNS groups, respectively. Similarly, mean Falls Efficacy Scale scores were also reduced by 10.7% (P = .001) in the nVNS-treated group and 12% (P = .003) in the sham group.

The investigators also observed a significant increase in brain-derived neurotrophic growth factor (BDNF) levels with treatment of nVNS, from 1946.7 pg/mL to 2204.1 pg/mg (P = .028), whereas those treated with the sham stimulation had BDNF levels decrease from 1943.7 pg/mL to 1682.7 pg/mL (P = .028)

"Parkinson disease is the fastest growing neurodegenerative disease in the United States. The impact of PD on patients and their families is devastating and the cost to the healthcare system is staggering. electroCore is looking forward to continuing research to bring nVNS to patients with PD,” Eric Liebler, senior vice president, Neurology, electoCore, said in a statement.1

GammaCore is the first non-invasive, hand-held therapy applied at the neck as an adjunctive therapy to treat migraine and cluster headache through the utilization of a mild electrical stimulation to the vagus nerve that passes through the skin. The therapy is FDA cleared in the United States for adjunctive use for the preventive treatment of cluster headache in adult patients, as well as the acute treatment of pain associated with episodic cluster headache in adult patients.

In February, the FDA cleared the expansion of the nVNS device’s label to include the preventive treatment of migraine in adolescent patients aged between 12 and 17 years.3 At the time, it became the first option acute and preventive for both adult and adolescent patients with migraine. A recently published review of cluster headache and its treatment options identified the gammaCore therapy as the only therapy shown to be effective for both the acute treatment of episodic cluster headache as well as the prevention of cluster headache in clinical trials.4

REFERENCES
1. electroCore announces publication of study on non-invasive vagus nerve stimulation (nVNS) to improve clinical outcomes and molecular biomarkers in Parkinson disease patients. News release. electoCore. June 2, 2021. Accessed June 2, 2021. https://www.globenewswire.com/news-release/2021/06/02/2240288/0/en/electroCore-Announces-Publication-of-Study-on-Non-Invasive-Vagus-Nerve-Stimulation-nVNS-to-Improve-Clinical-Outcomes-and-Molecular-Biomarkers-in-Parkinson-s-Disease-Patients.html
2. Mondal B, Choudhury S, Banerjee R, et al. Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson disease in patients with freezing of gait. Published online May 27, 2021. NPJ Parkinson’s Disease. doi: 10.1038/s41531-021-00190-x
3. electroCore Announces 510(k) Clearance of gammaCore™ Non-Invasive Vagus Nerve Stimulation (nVNS) to Treat Adolescent Migraine. News release. February 16, 2021. Accessed June 2, 2021. globenewswire.com/fr/news-release/2021/02/16/2176061/0/en/electroCore-Announces-510-k-Clearance-of-gammaCore-Non-Invasive-Vagus-Nerve-Stimulation-nVNS-to-Treat-Adolescent-Migraine.html
4. Wei DY, Goadsby PJ. Cluster headache pathophysiology — insights from current and emerging treatments. Nat Rev Neurol. 2021:17:308-324. doi: 10.1038/s41582-021-00477-w