The Effect of Urox™ in the Treatment of Overactive Bladder and Urinary Incontinence

Study Overview
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Brief Summary
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This study aims to assess the efficacy of a specialized herbal formula, Urox, versus control over 8 weeks, in a double blind, placebo controlled trial. 150 participants are being recruited, randomized and administered treatment or placebo for the period of 8 weeks after initial eligibility screening. Outcome measures include previously validated tools such as the 3 day symptom diary measuring self-recorded day frequency, nocturia, urgency and incontinence episodes. Quality of life improvements are being measured using the Incontinence Impact Questionnaire, Urinary Distress Inventory and the short version of the OverActive Bladder survey.

Detailed Description
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Initial consultations were held at either the Brisbane campus of the Endeavour College of Natural Medicine Naturopathic clinic or at Kelvin Grove Natural Medicine clinic, Brisbane. Follow up interviews are being conducted via telephone. To minimize dropout rates, participants are telephoned (as a reminder for the call and to complete the micturition diaries) approximately 1 week before the scheduled interview time and were intermittently called over the week following if they were unable to be reached at the scheduled interview time. Three attending clinicians interviewed trial participants, all having participated in interview training prior to any interviews being taken. The training was designed to ensure utility of a uniform and consistent approach regarding how questions were asked and how data was recorded. The week prior to an initial consultation participants were requested to complete a micturition diary and health related quality of life surveys, to serve as baseline measures. The attending clinician then also completed a clinical data sheet, at the time of the initial consultation, containing a range of questions including demographics, exercise, health history and habits, which will be used to control and correlate data variables. Any incomplete quality of life surveys at the outset were also completed at the first interview. Micturition diaries are collected by post at 2, 4 and 8 week intervals along with the completion of quality of life surveys and follow up clinical data sheet via telephone. Participants were asked to keep the micturition diary for 3 days prior to each consultation and were provided reply paid envelopes to return the surveys and unused capsules to assess compliance. For the primary outcome (day frequency) measure it was calculated that 90 participants equally divided into placebo and control were required to detect a difference of 1.6 urinary frequency episodes per day (2.7SD) between treatment and placebo groups, with a two-tailed alpha of 0.05 and a power of 80%. For total incontinence, 53 participants were required equally divided into each group to detect a difference of 1.2 episodes per day (2.2SD), while for urgency 54 was required in each group to detect a difference of 2 per day (3.7SD). To account for potential drop-outs and variations in presenting symptoms, a total of 150 participants were recruited. Data for the two treatments will be compared using mixed effects ordered logistic regression adjusted for repeated measures (Stata, version 13.1, StataCorp, TX, USA). GraphPad Prism (version 6.00 for Windows, GraphPad Software, La Jolla California, USA) will be used to plot the data. Data (day frequency, night frequency, urgency and incontinence) will be evaluated by intention to treat analysis, with the last result brought forward for people who dropped out or were lost to follow-up. Variables selected for adjustment using backward stepwise regression from list including age, sex, water intake and diuretic use (p<0.22 for covariate inclusion). Holm estimation test will be used to adjust p-values for repeated measures. Each analysis will only included participants who are symptomatic at baseline. For example, in relation to daytime urinary frequency - only participants with baseline of ≥10 will be included in the analyses.

Official Title
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The Effect of Urox™(Crateva, Horsetail and Lindera Combination) in the Treatment of Overactive Bladder and Urinary Incontinence

Conditions
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Overactive Bladder, Urinary Incontinence, Urinary Frequency or Urgency Adverse Event, Nocturia

Intervention / Treatment
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* Dietary Supplement: Urox
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria include symptoms of urinary frequency (at least ten times per day) and/or incontinence (at least nine episodes per week), provided they have experienced symptoms of OAB for at least 6 months. Exclusion Criteria: Recent surgery particularly hysterectomy or prolapse repair (within the last 12 months) Recently undergone childbirth (within the last 12 months), or currently pregnant. Use of any natural therapies for bladder symptoms in the last month. Concomitant health conditions such as uncontrolled diabetes mellitus, heart disease, pancreatic, hepatic or renal disease, recurrent urinary tract infections, and chronic inflammatory conditions, which may otherwise affect outcomes. Currently being treated for mental health issues or psychiatric disturbances. Any individuals who are presently taking prescribed medication for incontinence or OAB.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>2 capsules per day of the herbal formula (Urox®) with each capsule containing 420mg of a concentrated proprietary blend of extracts of Crateva nurvala stem bark, Equisetum arvense stem and Lindera aggregata root | Dietary Supplement: Urox<br>* Active treatment - Proprietary combination of Crateva nurvala, Equisetum arvense and Lindera aggregata herbs<br>|
| Placebo Comparator: Placebo<br>identical placebo vegetarian capsule containing color-matched cellulose | Other: Placebo<br>* Placebo - Identical vegetarian capsule containing color-matched cellulose to that of the active treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day Urinary Frequency | Day urinary frequency as defined as the number of voluntary diurnal micturitions per day, recorded in a validated urinary diary | 8 weeks | 
| Nocturia Frequency | Night time urinary frequency as defined as the number of voluntary nocturnal micturition's per day recorded in a validated urinary diary | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Urgency Frequency | Urinary urgency as defined by number of urgency episodes per day recorded in a validated urinary diary | 8 weeks | 
| Urge Incontinence Frequency | Urge incontinence as defined by number of incontinence episodes per day resulting from urinary urgency, recorded in a validated urinary diary | 8 weeks | 
| Stress Incontinence Frequency | Stress incontinence as defined by number of episodes of incontinence per day related to stress, recorded in a validated urinary diary | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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overactive bladder, urinary incontinence, nocturia, urinary frequency