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The goal of this clinical trial is to learn if probiotics can help improve symptoms in adults with overactive bladder (OAB) and anxiety. The main questions it aims to answer are:
Researchers will compare probiotics to a placebo (a look-alike powder that contains no active bacteria) to see if the probiotics work better to treat OAB and anxiety when both groups also use standard behavioral therapy (like bladder training).
Participants will:
Background and Scientific Rationale Overactive bladder (OAB) is a prevalent chronic condition that severely impairs patients' quality of life. Accumulating epidemiological evidence highlights a high comorbidity rate between OAB and psychological disorders, particularly anxiety. These two conditions often exacerbate each other, forming a vicious pathological cycle: anxiety heightens central sensitivity to bladder fullness, while unpredictable urinary urgency worsens psychosocial stress. Current pharmacological mainstays, such as antimuscarinics and β3-adrenoceptor agonists, primarily target local bladder smooth muscle. They often fail to address the underlying psychological comorbidities and are frequently associated with intolerable adverse effects (e.g., dry mouth, constipation), leading to high discontinuation rates. There is an urgent clinical need for systemic, well-tolerated therapeutic strategies that address both physical and emotional symptoms.
Theoretical Framework: The Brain-Gut-Bladder Axis This trial is grounded in the emerging "Brain-Gut-Bladder Axis" model. Chronic stress and anxiety can trigger systemic low-grade inflammation and alter the gut microbiome, which in turn influences peripheral neural pathways and bladder afferent signaling. We hypothesize that targeted microecological interventions using specific "psychobiotics" can modulate this axis. Scientific literature suggests that select probiotic strains can communicate with the central nervous system via the vagus nerve and systemic metabolites. By doing so, they may downregulate the hypothalamic-pituitary-adrenal (HPA) axis, optimize the levels of inhibitory neurotransmitters (such as GABA and Serotonin), and suppress neurogenic inflammation.
Intervention Strategy To test this hypothesis, this study employs an "add-on" clinical trial design. All enrolled participants will receive standardized behavioral therapy, which remains the fundamental first-line treatment for OAB, consisting of bladder training and lifestyle modification instructions. On top of this standard of care, participants will be randomized to receive either a multi-strain probiotic compound or a visually and organoleptically matched placebo.
The active intervention utilizes a compound of food-grade, widely recognized safe bacterial strains: Lactobacillus plantarum, Bacillus coagulans, Lactobacillus casei, and Lactobacillus acidophilus. These specific strains were selected for their documented potential in immune regulation, anti-inflammatory properties, and central nervous system modulation.
Study Execution and Clinical Significance Throughout the 12-week intervention period, the study avoids invasive procedures or the collection of extensive biological samples for complex genomic sequencing. Instead, it relies on validated clinical instruments, patient diaries, and standard routine urinalysis (strictly for safety monitoring and infection exclusion) to track treatment trajectories.
By bridging urology and neurogastroenterology, this study seeks to provide high-quality, evidence-based data for a paradigm shift in OAB management. If proven effective, this probiotic-assisted approach will offer a safe, non-pharmacological "mind-body" co-treatment option, potentially breaking the anxiety-urgency cycle and significantly improving the comprehensive well-being of a difficult-to-treat patient population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotics + Standard Behavioral Therapy | Experimental | Participants assigned to this arm will receive a probiotic powder compound containing Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus acidophilus. The probiotic powder will be dissolved in a glass of water and taken orally once a day for 12 weeks. In addition to the probiotic, participants will receive standard behavioral therapy for overactive bladder (OAB) administered by trained clinical staff. This comprehensive, individualized therapy includes six core modules: bowel management (e.g., dietary fiber intake), fluid and diet modification (e.g., limiting caffeine and other bladder irritants), weight and smoking management, bladder training (including voiding diaries, delayed voiding, and urge suppression techniques), pelvic floor muscle training (PFMT), and personalized follow-up adjustments. |
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| Placebo + Standard Behavioral Therapy | Experimental | Participants assigned to this arm will receive a placebo powder dissolved in a glass of water, taken orally once a day for 12 weeks. The placebo is composed of inert excipients (such as maltodextrin) and contains no active bacteria, but is identical to the active probiotic product in color, texture, taste, and solubility. In addition to the placebo, participants will receive the exact same standard behavioral therapy for OAB as the experimental group. This comprehensive, individualized therapy includes six core modules: bowel management, fluid and diet modification (e.g., limiting bladder irritants), weight and smoking management, bladder training (including voiding diaries, delayed voiding, and urge suppression techniques), pelvic floor muscle training (PFMT), and personalized follow-up adjustments. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Multi-strain Probiotic Compound | Dietary Supplement | The active intervention consists of a probiotic powder containing Lactobacillus plantarum DY-1, Lactobacillus casei KDB-LC, and Lactobacillus acidophilus KDB-03. The powder is to be dissolved in a glass of water and administered orally once a day for 12 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Mean Number of Micturitions per 24 Hours | Assessed using a 3-day voiding diary. Participants record every voiding event over 3 consecutive days. The metric is calculated as the total number of micturitions divided by 3 to determine the mean daily frequency. A negative change (decrease) from baseline indicates an improvement in overactive bladder symptoms. | Baseline (Week 0), Week 4, Week 8, and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Mean Number of Urgency Episodes per 24 Hours | Assessed using a 3-day voiding diary, where participants rate urgency for each voiding event on a 0-5 scale (0=no urgency, 5=severe urgency). The metric is calculated as the mean number of urgency episodes per day. A decrease in the number of episodes from baseline indicates symptom improvement. | Baseline (Week 0), Week 4, Week 8, and Week 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yan Li, doctor | Contact | +86 18560089113 | yanli@sdu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Yuchao Sun, Bachelor | Shandong University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Qilu Hospital of Shandong University | Jinan | Shandong | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27450939 | Background | Lai HH, Rawal A, Shen B, Vetter J. The Relationship Between Anxiety and Overactive Bladder or Urinary Incontinence Symptoms in the Clinical Population. Urology. 2016 Dec;98:50-57. doi: 10.1016/j.urology.2016.07.013. Epub 2016 Jul 19. | |
| 23195283 | Background | Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, Dorrepaal C, Martin N. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a beta(3)-adrenoceptor agonist, in overactive bladder. Eur Urol. 2013 Feb;63(2):296-305. doi: 10.1016/j.eururo.2012.10.048. Epub 2012 Nov 6. |
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| ID | Term |
|---|---|
| D053201 | Urinary Bladder, Overactive |
| ID | Term |
|---|---|
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C100843 | Lacteol |
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| Placebo | Other | An inactive placebo powder composed of inert excipients (maltodextrin) containing no active bacteria. It is visually and organoleptically identical to the active probiotic product (matching in color, texture, taste, and solubility). The powder is to be dissolved in a glass of water and administered orally once a day for 12 weeks. |
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| Change in the Mean Number of Urgency Urinary Incontinence (UUI) Episodes per 24 Hours | Assessed using a 3-day voiding diary, recording urine leakage (in mL). UUI is defined as the involuntary leakage of urine associated with urgency. The metric is calculated as the mean number of UUI episodes per day. A decrease from baseline indicates symptom improvement. | Baseline (Week 0), Week 4, Week 8, and Week 12 |
| Change in Mean Volume Voided per Micturition | Assessed using a 3-day voiding diary. The value is calculated by dividing the total volume of urine voided over the 3-day period by the total number of micturitions during that same period, measured in milliliters (mL). An increase from baseline indicates improved functional bladder capacity. | Baseline (Week 0), Week 4, Week 8, and Week 12 |
| Change in Generalized Anxiety Disorder-7 (GAD-7) Score | The GAD-7 is a standardized questionnaire used to measure the severity of anxiety. It consists of 7 items, each scored from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 21. Higher scores indicate greater severity of anxiety symptoms. A decrease in the total score from baseline indicates clinical improvement. | Baseline (Week 0), Week 4, Week 8, and Week 12 |
| Change in Overactive Bladder Symptom Score (OABSS) | The OABSS is a validated 4-item questionnaire assessing daytime frequency, nighttime frequency, urgency, and urgency urinary incontinence. The total score ranges from 0 to 15, derived from the sum of the four symptom scores. A higher score indicates more severe OAB symptoms. A decrease from baseline reflects clinical improvement. | Baseline (Week 0), Week 4, Week 8, and Week 12 |
| Change in Overactive Bladder Questionnaire (OAB-q) Score | Assessed using a 13-item health-related quality of life and symptom bother questionnaire (OAB-q). Each item is rated on a 6-point Likert scale from 1 (never) to 6 (all the time). The total score ranges from 13 to 78. A higher score indicates worse symptom bother and a greater negative impact on the patient's quality of life. A decrease in score indicates improvement. | Baseline (Week 0) and Week 12 |
| Patient Global Impression of Improvement (PGI-I) Score | The PGI-I is a single-item questionnaire assessing the patient's overall perception of their OAB symptom condition compared to baseline. Participants rate their condition on a 7-point scale ranging from 1 ("very much better") to 7 ("very much worse"). A lower score indicates a better treatment outcome. | Week 12 |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Safety and tolerability will be evaluated by monitoring the frequency, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) reported by participants throughout the study period. | From Baseline (Week 0) up to Week 12 |
| 33828554 | Background | Zhao W, Peng C, Sakandar HA, Kwok LY, Zhang W. Meta-Analysis: Randomized Trials of Lactobacillus plantarum on Immune Regulation Over the Last Decades. Front Immunol. 2021 Mar 22;12:643420. doi: 10.3389/fimmu.2021.643420. eCollection 2021. |
| 38078701 | Background | Smith AL, Berry A, Brubaker L, Cunningham SD, Gahagan S, Kane Low L, Mueller M, Sutcliffe S, Williams BR, Brady SS; the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. The brain, gut, and bladder health nexus: A conceptual model linking stress and mental health disorders to overactive bladder in women. Neurourol Urodyn. 2024 Feb;43(2):424-436. doi: 10.1002/nau.25356. Epub 2023 Dec 11. |
| 24316095 | Background | Bradley CS, Nygaard IE, Torner JC, Hillis SL, Johnson S, Sadler AG. Overactive bladder and mental health symptoms in recently deployed female veterans. J Urol. 2014 May;191(5):1327-32. doi: 10.1016/j.juro.2013.11.100. Epub 2013 Dec 6. |
| 29320672 | Background | Chung E, Lee D, Gani J, Gillman M, Maher C, Brennan J, Johns Putra L, Ahmad L, Chan LL. Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder. Med J Aust. 2018 Jan 15;208(1):41-45. doi: 10.5694/mja16.01097. |
| 31039103 | Background | Lightner DJ, Gomelsky A, Souter L, Vasavada SP. Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019. J Urol. 2019 Sep;202(3):558-563. doi: 10.1097/JU.0000000000000309. Epub 2019 Aug 8. |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D059411 | Lower Urinary Tract Symptoms |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |