Variable frequency stimulation (VFS) is a novel pattern of neuromodulation by delivering both high frequency stimulation (HFS) and low frequency stimulation (LFS) in a single output sequence. The purpose of this study is to evaluate the efficacy and safety of VFS mode of sacral neuromodulation in the treatment of refractory lower urinary tract dysfunction (LUTD).

The study was divided into two stages. Stage I: The preliminary experiment used self-control to explore the efficacy of VFS compared with CFS. Stage II: a randomized, blinded, 2 × 2 cross-over controlled trial was done, patients who participated in Stage I received washout for 7±3 days (the washout data were used as baseline data). After entering stage II, all patients were randomly divided into Group A (CFS-washout-VFS) and Group B (VFS-washout-CFS) in a 1:1 ratio. The CFS and VFS period were sustained for12 weeks respectively, and the washout time between CFS and VFS was 7 ± 3 days. Every 6 weeks was an interval for a follow-up. Voiding diary for 3 days, OABSS score, VAS score, OAB-qol score, HRQoL score and adverse events were collected.

15 patients were enrolled and completed assessments at stage I from June 2020 to December 2020. The number of voids was reduced from 14.05 ± 7.61 in the CFS mode to 12.61 ± 10.49 times. The treatment success rate was 80% after 6 weeks of VFS mode. 55 patients were included and completed the study in stage II, 28 and 27 patients were assigned in Group A and B, respectively. The demographic data (age, height, BMI, etc.) were not statistically different between the two groups, and the disease duration was 7.24 ± 8.65 years and 9.59 ± 11.94 years in Group A and Group B, respectively. During the VFS mode in both groups, a total of 38 subjects were treated with a combination of all-low frequency stimulation (LFS), 4 subjects with a combination of low frequency + high frequency stimulation (HFS) (frequency ≥ 30 Hz as high frequency), and 13 subjects with a combination of HFS. At the 24-week follow-up after system upgrade, the number of voids decreased from baseline by 7.26 ± 7.68 and 3.18 ± 4.04 in Group A and B, respectively, and there was a significant difference between the two groups (p = 0.017). The improvement rate of micturition frequency at the last (24-week) follow-up was 25.85% and 19.28% in Group A and B, respectively, but there was no significant difference between the two groups. Group A showed significant improvement from baseline in voided volume, OAB-qol symptom score, and HRQoL score ( p < 0.05); Group B showed significant improvement from baseline only in OAB-qol score and HRQoL score (p < 0.05), but there was no significant difference between the two groups. Among them, 97.78% and 75.91% had improvement from baseline in voiding volume and 45.36% and 25.96% had improvement in urgency score in voiding diary, respectively. In this clinical study, the overall incidence of adverse events was 5.26%. The main adverse events were intermittent fever (1/57, 1.75%), pain or strong irritation at the stimulation site (2/57, 3.51%). No surgery-related adverse events and adverse events related to the investigational device occurred. No serious adverse events occurred.

In this study, we found that the efficacy of VFS mode was not inferior to CFS mode.

The VFS mode of SNM is not inferior to the traditional CFS mode in improving the symptoms of OAB in patients with refractory LUTD, and can effectively improve the symptoms, and improve the quality of life, but it is still necessary to study the optimal stimulation parameters of different subjects.