Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis

Abstract

BackgroundGastric electric stimulation (GES) is a treatment approach to refractory gastroparesis, possibly acting centrally via afferent vagus nerve stimulation (VNS). Non-invasive VNS (nVNS) is a potential alternative to GES that could eliminate the safety risks of or identify likely responders to implantable neurostimulators.ObjectiveThis open-label proof-of-concept study assessed the effects of nVNS in patients with severe drug-refractory gastroparesis.MethodsPatients used the Gastroparesis Cardinal Symptom Index (GCSI) to grade symptoms in diaries daily for 2 weeks before treatment (baseline) and during ≥3 weeks of nVNS therapy. Adverse events (AEs) were also diarised. Treatment was self-administered using an nVNS device (gammaCore, electroCore) and consisted of 120 s stimulations to the vagus nerve in the neck (two stimulations to each side three times daily during weeks 1 and 2; three stimulations to each side three times daily during week 3 and beyond). Response was defined as a ≥1 point decrease from baseline in GCSI score.ResultsThirty-five patients enrolled; 23 were compliant with study procedures and were included in the analysis; 7 continued treatment beyond 3 weeks. Response rates were 35% (8/23) at 3 weeks and 43% (10/23) for the duration of therapy (3–6 weeks). For the entire cohort and the 10 responders, improvements from baseline were noted for mean total GCSI and GCSI subscale scores (nausea/vomiting, postprandial fullness/early satiety, bloating). No serious AEs were reported.ConclusionsThese preliminary results provide a signal that nVNS may be useful for treating refractory gastroparesis. Larger controlled studies are warranted.

Open‐label pilot study: Non‐invasive vagal nerve stimulation improves symptoms and gastric emptying in patients with idiopathic gastroparesis

“…The validity of our definition was supported by the clear divergence in scores between responders and non‐responders, and was consistent with a similar 40% response rate using the most up‐to‐date FDA‐recommended guideline for GCSI‐dd, in which a meaningful response is considered to be a 30% decrease or >0.50 decrease from baseline in at least 50% of the days or weeks of treatment. In a mixed cohort of medically refractory gastroparesis patients awaiting GES implantation, Paulon et al reported a similar 43% aggregate GSCI improvement after 3‐6 weeks of nVNS with the gammaCore device, with the largest symptom benefit occurring in the nausea/vomiting GCSI‐dd subscale . In our study of idiopathic gastroparesis, the largest symptom improvement occurred in the fullness/early satiety/appetite subscale, which also happened to be the most severe in our cohort.…”

“…This open‐label pilot study suggests that short‐term nVNS may have important clinical utility in mitigating the cardinal symptoms of gastroparesis in a subset of patients. Although our findings are consistent with a prior proof‐of‐concept study in medically refractory gastroparesis, our results are tempered by a lack of placebo control group, a small cohort, and a prophylactic daily dosing regimen vs an on‐demand‐for‐flare design of this study. Follow‐up placebo‐controlled, larger trials will be instrumental in determining if nVNS will become a clinical modality for gastroparesis therapy.…”

“…Patients self‐administered bilateral transcutaneous cervical non‐invasive vagal nerve stimulation (nVNS) twice daily for a minimum of four weeks using the gammaCore hand‐held vagal nerve stimulator (electroCore Inc). Twice daily stimulation was selected based on a standing prophylactic approach (rather than as needed for acute flares), prior studies showing efficacy with q12h dosing for episodic headaches, and personal communications revealing difficulty maintaining compliance with three times a day dosing, as reported by Paulon et al nVNS was delivered via two stainless steel contact surfaces that were coated with conductive gel before each treatment, and the device was positioned in parallel with the carotid pulse in the neck (Figure S1). A single stimulation of nVNS was programed as a 2‐minute period.…”

“…When studied in patients with primary headache, the device demonstrated a favorable safety profile and was not associated with significant adverse events . Recently, a proof‐of‐concept study reported clinical improvement in approximately 40% of drug‐refractory gastroparesis patients after 3 weeks of nVNS . Building on the proposed mechanism of action of GES and on the work of Paulon et al, the aim of the present open‐label pilot study was to assess the impact of short‐term nVNS on cardinal symptoms, gastric emptying, and autonomic function in patients with mild to moderate idiopathic gastroparesis.…”

“…9 Recently, a proof-of-concept study reported clinical improvement in approximately 40% of drug-refractory gastroparesis patients after 3 weeks of nVNS. 10…”