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

Official title

A Multicenter Randomized Controlled Trial Assessing the Efficacy and Safety of Pregabalin Combined With Educational and Behavioral Intervention Program 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.

Detailed description

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.

Interventions

• Behavioral Educational and Behavioral Management Program (EBMP)
  Standardized educational and behavioral intervention for IC/BPS patients, including bladder health education, dietary adjustment guidance, pelvic floor behavioral training, lifestyle modification and regular follow-up counseling. Identical EBMP content is delivered to participants in both study arms throughout the 12-week trial period.
• Drug Pregabalin
  Flexible oral dose titration scheme. Initial daily dosage is 150 mg split into 2-3 administrations. Dosage can be raised to 300 mg/day after 3-7 days, then further escalated by 150 mg every 3-7 days based on patient tolerance and symptom relief. The maximum daily dosage is capped at 600 mg. Dosage will be down-titrated to the maximum tolerated dose once intolerable adverse events occur, with stable dosing maintained until Week 12. This medication is only administered to the combined-treatment ar

Primary outcome measures

• Proportion of Treatment Responders Assessed by Global Response Assessment (GRA) [Time frame: 12 weeks after intervention initiation]

Secondary outcome measures (4)

• Changes in Pelvic Pain and Urgency/Frequency (PUF) Scale Scores [Time frame: Baseline (Day 0), Week 1, Week 3, Week 5, Week 6, Week 12]
• Changes in ICSI score [Time frame: Baseline (Day 0), Week 1, Week 3, Week 5, Week 6, Week 12]
• Incidence and Severity Grading of Adverse Events [Time frame: Entire study period with assessments at Day 0, Week 1, Week 3, Week 5, Week 6, Week 12]
• Changes in ICPI score [Time frame: Baseline (Day 0), Week 1, Week 3, Week 5, Week 6, Week 12]

Eligibility criteria

Inclusion Criteria:- Adults aged 18 years and older

• Clinically diagnosed with bladder pain syndrome/interstitial cystitis (IC/BPS) in accordance with diagnostic criteria released by AUA and ESSIC, with confounding disorders excluded through clinical workup
• Persistent urinary symptoms across most days in the latest 3 months prior to enrollment
• Participants report bladder pain/discomfort and urinary urgency/frequency scores ≥ 3 on the 0-10 Likert scale over the past 4 weeks

Exclusion Criteria:- Symptomatic urethral stricture

• Active neurological diseases that impair bladder or intestinal function
• Active autoimmune disorders or infectious diseases
• History of cystitis secondary to tuberculosis, pelvic radiotherapy or pelvic chemotherapy
• Previous history of non-cutaneous malignant tumors
• Confirmed severe psychiatric disorders at present, including major depressive disorder, bipolar disorder, schizophrenia and other serious mental illnesses
• Severe systemic diseases featuring obvious dysfunction of the heart, lung, liver or kidney
• Confirmed hypersensitivity to pregabalin
• Concomitant use of additional antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs)
• Pregnancy status
• Lactation period

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07752134 · 2026YJSKTPG-2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗