Efficacy and Safety of Pregabalin Combined With Educational and Behavioral Intervention for Bladder Pain Syndrome/Interstitial Cystitis

Overview

Bladder pain syndrome/interstitial cystitis (IC/BPS) brings long-term pelvic pain, frequent urination and poor sleep quality, which severely lowers patients' daily life quality. Educational and behavioral management program (EBMP) is a mainstream non-drug treatment for IC/BPS, yet a considerable proportion of patients fail to achieve satisfying symptom relief via EBMP alone. This multicenter randomized controlled trial aims to compare the efficacy and safety of pregabalin combined with EBMP versus EBMP monotherapy in adult IC/BPS patients. A total of 140 eligible adult participants fulfilling AUA and ESSIC diagnostic criteria for IC/BPS will be randomized at a 1:1 ratio into two groups. The control group receives standalone EBMP intervention, while the intervention group obtains EBMP plus pregabalin with flexible dosage titration. Pregabalin starts at 150 mg per day, and doses can be gradually adjusted up to a maximum daily limit of 600 mg according to patients' tolerance and symptom improvement during the 12-week intervention period. All enrolled participants will complete standardized symptom questionnaires, pain scoring and voiding diary assessments at predefined follow-up time points. The primary outcome is treatment response measured by Global Response Assessment (GRA) after 12 weeks of intervention. Secondary evaluations cover VAS pain scores, PUF, ICSI, ICPI scales, bladder functional parameters, quality of life, sleep status and depressive symptoms. Researchers will track all adverse events throughout follow-up to judge the safety of combined treatment. Findings from this trial can offer optimized treatment options for adults diagnosed with IC/BPS.

This prospective multicenter parallel randomized controlled trial adopts both intention-to-treat and per-protocol statistical analyses to compare combined pregabalin plus educational-behavioral intervention against behavioral intervention alone for IC/BPS management. Sample size calculation was performed via PASS 11 software. With the presumed 45% response rate of standalone EBMP and an expected 70% response rate in the combined-treatment arm, bilateral α=0.05 and statistical power of 80% were set for calculation. Allowing for a 10% participant dropout rate, the final planned enrollment is 70 subjects per group (140 participants in total). Random allocation is conducted through the sealedenvelope.com online platform, with allocation concealment realized by sealed opaque envelopes managed by an independent research assistant who is isolated from data collection and direct patient contact. The trial uses an open-label design for both treating clinicians and participants, while outcome assessors remain blinded to group allocation to reduce evaluation bias. Eligible adults must meet formal AUA and ESSIC IC/BPS diagnostic benchmarks, with urinary symptoms persisting across most days in the latest 3 months and baseline bladder discomfort scores no lower than 3 on the 0-10 Likert scale. Patients satisfying predefined exclusion criteria such as neurogenic bladder dysfunction, severe uncontrolled systemic diseases, pregabalin hypersensitivity, pregnancy and lactation will not be enrolled. For the combined-treatment arm, pregabalin titration strictly follows the preset dose-escalation protocol. Once intolerable adverse reactions emerge, dosage will be rolled back to the maximum tolerable dose that is maintained until the 12-week endpoint. SPSS 25.0 will be utilized for subsequent statistical analyses. Normal continuous variables will be expressed as mean ± standard deviation, non-normal metrics will be presented with median and interquartile ranges, and appropriate parametric or non-parametric statistical tests as well as chi-square/Fisher's tests will be selected in line with data distribution features, with statistical significance set at P \< 0.05. Rigorous source-data monitoring will be implemented across all involved medical centers throughout the whole trial course.