Variable- versus constant-frequency sacral neuromodulation in black-zone overactive bladder patients: a study protocol for a multicenter, prospective, randomized, blind, self-controlled trial

Background: The curative effect of sacral neuromodulation (SNM), used to treat overactive bladder (OAB) patients, is definite. However, some patients still have recurrent symptoms after SNM and unsatisfactory symptom improvement after repeated adjustments of the stimulation parameters combined with oral drugs. These are referred to as black-zone OAB patients. The described SNM is the standard method, which involves a constant-frequency stimulation (CFS) of the patient's specific sacral nerve. A new treatment strategy, which combines the advantages of high-frequency and low-frequency stimulations to generate variable-frequency stimulation (VFS), has not yet undergone a formal randomized clinical trial. Therefore, we designed this clinical trial to evaluate the efficacy and safety of VFS-SNM and CFS-SNM in the treatment of black-zone OAB patients. Methods: We designed a multicenter, prospective, randomized, blinded, self-controlled trial with a 12week follow-up period. The trial randomly divides the enrolled patients into CFS-SNM and VFS-SNM groups. The main evaluation index is the comparative effectiveness of VFS-SNM and CFS-SNM at the last follow-up. The secondary evaluation indices include the change in the OAB symptom score, the quality of life (QOL) score, and the visual analog scale compared with the baseline period at each follow-up time point. Discussion: Previous studies and our pre-experimental results suggest that black-zone OAB patients may benefit from VFS-SNM. Twelve weeks of VFS-SNM are effective in 40%, and the non-inferior cutoff value is 10% (80% power, 0.05 significance level, 20% loss to follow up). Thus, the calculated sample size is 37 cases each for CFS and VFS groups. The trial is expected to be carried out in 18 centers, but centers will be added or removed as appropriate depending on specific implementation conditions. Clinical researchers at each center will be responsible for screening qualified participants. This is the first randomized controlled trial to comprehensively evaluate the efficacy and safety of VFS-SNM in black-zone OAB patients, which will provide high-quality clinical evidence and may provide new clinical options for such patients.