Idiopathic overactive bladder symptoms (OAB) have a profound impact on the quality of life of the affected individuals. Although several treatment options are available, each of them is associated with significant drawbacks, which limit their wide use in clinical practice [1].
The Peroneal electric Transcutaneous NeuroModulation (Peroneal eTNM®) is a new fully noninvasive neuromodulation method based on selective stimulation of the peroneal nerve.  The URIS® neuromodulation system, engineered to deliver Peroneal eTNM®, consists of the URIS® device, URIS® active electrodes, and the biofeedback foot sensor (BFS). The unique design of the URIS® device and URIS® active electrodes allows for the use of a low voltage during neuromodulation, which significantly reduces the unpleasant sensations. The BFS allows for precise localization of the active electrodes and for continuous adjustment of the stimulation parameters during the stimulation session to achieve the optimal therapeutic effect. 
In the initial pilot study, peroneal eTNM® showed excellent efficacy and tolerability in the out-patient office setting [2]. The aim of the present study was to evaluate the efficacy and safety of peroneal eTNM® using URIS® neuromodulation system performed by patients with refractory OAB themselves in home-based setting.

This study was designed as a prospective open-label, multicenter trial. The study protocol was approved by independent Institutional Review Board at each study center and all participants provided informed consent.
The study enrolled adult female patients with a clinical diagnosis of refractory idiopathic OAB. The inclusion criteria at baseline included failure of at least one therapeutic attempt during one-year prior to enrollment and ≥ one urgency episode grade 3 or grade 4 according to Patients Perception of Intensity of Urgency Scale (PPIUS) in course of 24 hours and frequency ≥ 8 times/24 hours as documented using the 7-day bladder diary. The exclusion criteria included urinary tract infection, significant prolapse of the pelvic organs, history of previous malignant disease in the pelvic area and any neurological disease that may affect urinary bladder function, among others.  
Enrolled patients were treated with peroneal eTNM® using the URIS® neuromodulation system (STIMVIA®, Ostrava, Czech Republic) in their homes for 30 minutes daily for 6 weeks.    
The 7-day bladder diary, OAB V8 questionnaire, Treatment satisfaction visual analogue scale (TS VAS) and Pain perception visual analogue scale (PP VAS) were used to assess treatment efficacy and tolerability. The safety assessments included monitoring of the incidence and severity of adverse events (AEs).
The primary endpoint was defined as proportion of subjects with ≥ 50% reduction in average daily number of severe urgency episodes after six weeks of therapy. 
Statistical analyses were performed with GraphPad Prism 9.0.0 (GraphPad Software, Inc., San Diego, CA). A non-parametric one-way ANOVA Friedman test was used to compare the changes of categorical variables, while Wilcoxon rank-sum tests were used to assess the changes of the non-categorical variables. P-value < 0.05 was considered statistically significant. No correction for multiple testing was applied.

In total, 40 subjects were screened for the study, 29 of them met the inclusion criteria at BL and were enrolled and ultimately included into the Full Analysis Set. Key participant demographics include: age (median [min.-max.]) 62 [42-77] years, BMI (mean [±SD]) 28 [5.6] and duration of OAB symptoms (median [95%CI]) 6 [4-10] years. Twenty-five out of 29(86%) and 23/29 (79%) of patients were classified as responders at week 4 and at End of Treatment (EoT) visit, respectively. Changes in absolute number of severe urgency episodes are shown in Figure 2. There was significant reduction in urinary frequency from baseline to EoT (p<0.001), number of grade 3 urgency episodes (p< 0.001), number of grade 4 urgency episodes (p=0.001) and number of nocturia episodes (p=0.002). The OAB V-8 score also showed significant improvement (p<0.001), reducing the baseline OAB-V8 score by a median of -38% (-51% to -17%, 95% CI). There was a significant improvement in the TS VAS by 230% from 20 (15 to 29, 95% CI) to 66 (30 to 86, 95% CI) (p<0.001).
Overall, the therapy was very well tolerated. Pain perceived during peroneal eTNM® sessions as rated using PP VAS was 0 (0 to 1.5, IQR) at week 1 and 0 (0 to 3.5, IQR) at EoT. 
There were 24 AEs recorded, two of them were considered treatment-related. One participant reported light superficial skin abrasion at the contact point with the active electrode and another participant noted limited ability to move the toes of the left foot for several minutes after a session was completed. Both events were considered mild and did not require any intervention. Both patients recovered with no sequelae and completed the study according to the protocol.

This study documented a significant reduction in all OAB symptoms and an improvement in all patient-reported outcomes in a cohort of female patients with refractory OAB, treated with peroneal eTNM® using the URIS® neuromodulation system. The peroneal eTNM® showed favorable safety profile with very low incidence of treatment-related adverse events. Recording of patients’ perception of pain/discomfort during treatment confirmed excellent tolerability of the peroneal eTNM®. Based on PP-VAS scores reported in this study, the method can be considered very close to painless. The data document that peroneal eTNM® can be performed by patients themselves after minimal training at home.

The data collected in this study provide the initial evidence that peroneal eTNM® using the URIS® neuromodulation system is effective and safe method for the home-based treatment of OAB. Further research is required to confirm its long-term efficacy and safety and to assess the optimal neuromodulation schedule.

Nitti VW, Patel A, Karram M. Diagnosis and management of overactive bladder: A review. J Obstet Gynaecol Res. 2021; 47(5): 1654-1665.
Krhut J, Rejchrt M, Skugarevska B, Grepl M, Zvara P. Peroneal Electrical Transcutaneous NeuroModulation as a New Treatment for Patients with Overactive Bladder: An Initial Clinical Experience. Urol Int. 2022 Mar 22:1-6. doi: 10.1159/000522570. Epub ahead of print.

Continence 2S2 (2022) 100358
DOI: 10.1016/j.cont.2022.100358