Bryophyllum Pinnatum Versus Solifenacin Versus Placebo for Overactive Bladder

Study Overview
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Brief Summary
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Overactive bladder (OAB) is an enigmatic condition that is treated symptomatically with anticholinergic drugs (gold standard 2013). In a clinical pilot study was found to be a trend for a higher reduction of the micturition frequency in the Bryophyllum pinnatum group - treated with chewing tablets containing 50% of dried BP leaf press juice - than in the placebo group (n=20, p=0.064) Hypothesis: To test the superior effectivity of Bryophyllum versus Placebo in the treatment of OAB with the needed number (Purpose 1) and to assess in an experimental arm the side effects of BP in comparison to the standard drug (Vesicare) in a clincial trial (Purpose 2).

Detailed Description
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In a US nation-wide survey, lower urinary tract symptoms are one of the strongest predictors that patients will seek complementary and alternative medicine (CAM) care. In comparison to general gynecological patients, urogynecological patients are particularly prone to seek help in CAM. Moreover out of the different CAM options, herbal medication is one of the most preferred treatments. However, the effectiveness of CAM regarding OAB has not yet been adequately and objectively evaluated. Therefore, it is timely and essential to elucidate the mode of action as well as to prove efficacy of herbal treatments by a translational approach including comprehensive in vitro experimentation and randomized controlled clinical trials. Bryophyllum pinnatum and specially the flavonoid components have shown a muscle relaxing effect on porcine bladder strips. Study Design: Multicenter, prospective, double-blind randomized, placebo-controlled cross-over study, phase III to test the superiority of Bryophyllum pinnatum (BP) over placebo in the treatment of overactive bladder. In this cross-over trial a total of 30 patients is needed to proof the superiority of BP over placebo (5 randomization blocs, each 6 patients). Each patient gets each of the three study drugs (BP, Solifenacin, Placebo) in a double-blind randomization. The number of patients was calculated in a post-hoc analysis based on the primary endpoint of a previous study (reduction of micturition rates/24hours; 9.5 (SD2.2) before and 7.8 (SD1.2) after Bryophyllum versus 9.3 (SD1.8) before and 9.1(SD1.6) after placebo), under the assumption of a normal data distribution and a power of 80% a patient number of 2x20. Plus 10% for non-parametric tests in the case of a non-normal distribution (Wilcoxon) were added, what generated a number of 2x22 patients. In order to facilitate an equality in the randomization, the investigator choose a cross-over design. Due to the length of the study time, the drop-out rate was risen from 10 to 20% what yielded under the assumption of a equal block randomization the number of 30 patients. Additionally, an explorative arm containing the standard medication Vesicare was inserted, as this is of great clinical interest. For this explorative comparative arm are no existing data that would allow to do a power calculation. This follow-up study will give a compelling answer on the efficacy or non-efficacy of BP as well as the safety of BP in respect to placebo and possible answers of its position regarding the standard medication Vesicare.

Official Title
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Treatment of Patients With Overactive Bladder With Bryophyllum Pinnatum Versus Solifenacinsuccinat Versus Placebo: Multicenter, Prospective, Double-blind Randomized, Placebo-controlled Cross-over Study, Phase III Trial

Conditions
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Overactive Bladder, Urge Urinary Incontinence

Intervention / Treatment
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* Drug: Bryophyllum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OAB (>8 micturitions/24 hours, associated with urge symptoms) postmenopausal women cystoscopy to exclude a bladder carcinoma or carcinoma in situ written and oral informed consent Exclusion Criteria: urinary tract infection in an intermittent catheter asservated sample (>1000 bacterias/ml) intake of bladder affecting drugs like anticholinergics, diuretics, muscle relaxing medications and phytotherapeutics in the last three months neurological conditions such as stroke, multiple sclerosis, spinal cord injury or Parkinsons's disease postvoid residual volume ≥100 ml lactose intolerance contraindication for Solifenacin

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bryophyllum<br>50% in 350mg Lactose, 2-2-2 | Drug: Bryophyllum<br> <br> * Other names: provided by Weleda AG, Arlesheim, Switzerland;|
| Placebo Comparator: Placebo<br>Lactose 350mg, 2-2-2 | Drug: Bryophyllum<br> <br> * Other names: provided by Weleda AG, Arlesheim, Switzerland;|
| Experimental: Solifenacin<br>10mg in 350mg Lactose, 2-2-2 | Drug: Bryophyllum<br> <br> * Other names: provided by Weleda AG, Arlesheim, Switzerland;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the micturition frequency | assessment of the voiding frequency in the 3-day bladder at visit 2,3,4,5,6 | participants will be followed for the duration of the study, an expected average of 35 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in quality of life parameters | assessment with quality of life and symptom burden questionnaires at visit 2,3,4,5,6 (questionnaires ICIQ-OAB and KHQ) | participants will be followed for the duration of the study, an expected average of 35 weeks | 
| Voiding diary parameters | 3-day bladder diary returned at visit 2,3,4,5,6 | participants will be followed for the duration of the study, an expected average of 35 weeks | 
| Assessments of the patient's compliance | drug intake protocol and counting of the returned tablets | participants will be followed for the duration of the study, an expected average of 35 weeks | 
| Assessment of AE/SAE | AE/SAE protocol | participants will be followed for the duration of the study, an expected average of 35 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Female, Postmenopause