Efficacy of Probiotics for OAB Patients With Anxiety

Official title

Evaluating the Efficacy of Probiotics as an Adjunct to Behavioral Therapy in Patients With Overactive Bladder (OAB) and Anxiety Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial

Overview

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: 1. Does taking probiotics lower the number of times participants need to urinate in a 24-hour period? 2. Does taking probiotics lower participants' anxiety levels? 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: 1. Take probiotics or a placebo twice a day for 12 weeks. 2. Learn and practice bladder training using a manual and educational videos. 3. Keep a 3-day diary of when they urinate and what they drink at the beginning, middle, and end of the study. 4. Answer survey questions about their anxiety and quality of life during clinic visits. 5. Provide urine samples for routine checkups to ensure they do not have infections.

Detailed description

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.

Interventions

• Dietary supplement Multi-strain Probiotic Compound
  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.
• Other Placebo
  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.

Primary outcome measures

• Change in the Mean Number of Micturitions per 24 Hours [Time frame: Baseline (Week 0), Week 4, Week 8, and Week 12]

Secondary outcome measures (8)

• Change in the Mean Number of Urgency Episodes per 24 Hours [Time frame: Baseline (Week 0), Week 4, Week 8, and Week 12]
• Change in the Mean Number of Urgency Urinary Incontinence (UUI) Episodes per 24 Hours [Time frame: Baseline (Week 0), Week 4, Week 8, and Week 12]
• Change in Mean Volume Voided per Micturition [Time frame: Baseline (Week 0), Week 4, Week 8, and Week 12]
• Change in Generalized Anxiety Disorder-7 (GAD-7) Score [Time frame: Baseline (Week 0), Week 4, Week 8, and Week 12]
• Change in Overactive Bladder Symptom Score (OABSS) [Time frame: Baseline (Week 0), Week 4, Week 8, and Week 12]
• Change in Overactive Bladder Questionnaire (OAB-q) Score [Time frame: Baseline (Week 0) and Week 12]
• Patient Global Impression of Improvement (PGI-I) Score [Time frame: Week 12]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: From Baseline (Week 0) up to Week 12]

Eligibility criteria

Inclusion criteria

• Aged between 18 and 80 years old (inclusive).
• Able to understand study-related instructions and independently complete the required questionnaires.
• Able to provide written informed consent and willing to comply with all study requirements, including completing diaries/questionnaires and refraining from taking any other probiotic or prebiotic supplements during the 3-month study period.
• Meet the diagnostic criteria for Overactive Bladder (OAB) as defined by the International Continence Society (ICS) (urgency as the core symptom, with or without urgency urinary incontinence, frequency, and nocturia); have an Overactive Bladder Symptom Score (OABSS) ≥ 6; and have a daytime voiding frequency of ≥ 8 times.
• Have a preliminary diagnosis of "Generalized Anxiety Disorder" or "Anxiety state" assessed by a psychiatrist or trained investigator according to DSM-5 or ICD-10 criteria, or have a Generalized Anxiety Disorder-7 (GAD-7) scale score ≥ 5.
• If previously using any over-the-counter medications or other products for anxiety relief (e.g., magnesium, melatonin, anticholinergic drugs) or receiving psychotherapy, these must have been discontinued for at least 4 weeks prior to randomization and must remain completely discontinued throughout the entire study period.

Exclusion criteria

• Presence of organic diseases of the urinary system (e.g., urinary tract obstruction, tumors, stones, acute infection, interstitial cystitis, stress urinary incontinence).
• Neurogenic bladder caused by neurological diseases or a history of pelvic surgery.
• Use of antibiotics, probiotics, or prebiotics within the past 1 month prior to screening.
• Any adjustment to medications used for treating OAB or anxiety within the past 2 weeks prior to screening.
• Pregnant or lactating women, or individuals with a known allergy to any components of the study preparation.
• Suffering from other severe psychiatric/psychological disorders or severe systemic diseases (e.g., uncontrolled diabetes mellitus, severe obesity).

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

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Qilu Hospital of Shandong University — Jinan

Publications

• 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. PMID 27450939
• 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. PMID 23195283
• 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. PMID 33828554
• 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 20 PMID 38078701
• 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. PMID 24316095
• 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. PMID 29320672
• 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. PMID 31039103

Identifiers

NCT: NCT07635212 · KYLL-2026-03-006-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗