Urinary Microbiome Changes Following Administration of 500 mg of NDS-446 in Women With Dry OAB at 12 Weeks

Study Overview
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Brief Summary
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The purpose of this study is to learn about how the use of 500 mg of dried cranberry powder extract (NDS-446) changes the bacteria that normal reside in the bladder of women who don't have urinary leakage problems but do have problems with urinary urgency and frequency.

Detailed Description
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While this treatment algorithm is the recommended approach to OAB management, recent research has resulted in the development of a new paradigm that may influence how this condition is treated in the future. This research focuses on the urinary microbiome and for a decade it has been known that urine is not sterile. Expanded Quantitative Urine Culture (EQUC) techniques have allowed for more comprehensive and accurate 16S ribosomal RNA sequencing of the urinary microbiome. Changes in the abundance and diversity of the resident microbiota have been associated with a number of urogenital conditions including interstitial cystitis, urinary incontinence, responses to OAB medications and symptoms of urinary tract infections. These studies provide insight to the fact that the microbiome plays an important role in the maintenance of a healthy urogenital tract. Thus, treatments that target the microbiome for one condition may work for others by similar mechanisms, especially when there is considerable symptom overlap between the two conditions as there is in UTIs and OAB. One such treatment is cranberry (Vaccinium macrocarpon) extract, which has long been used as complementary therapy for a variety of medical conditions. Health benefits are linked to the presence of phytochemicals present in the fruit- anthocyanins, flavonols, tannins, proanthocyanidins, and phenolic acid derivatives. Cranberry is known to be effective in the prevention of UTIs. In a recent study examining its use in women with dry OAB, daily dried cranberry improved urgency symptoms and number of daytime voids. In addition, the authors reported an improvement in the validated subjective instrument, Patient Perception of Bladder Condition (PPBC). Moderately symptomatic LUTS in men improved following 6 months of daily dried cranberry powder. Therefore, the investigators aim to investigate changes to the female urinary microbiome in women with dry OAB who take daily dried cranberry extract. This study aims to quantify a change in urinary frequency, urinary urgency, and PPBC following the daily use of a cranberry extract called NDS-446. The investigators also have an ancillary hypothesis that women who are post-menopausal will develop a urinary microbiome more similar to pre-menopausal women by the end of the study. Lastly, the investigators will measure the levels of extracellular (eATP) in the urine of participants. It has been previously shown that higher levels of eATP are associated with worsening OAB symptoms.

Official Title
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Urinary Microbiome Changes Following Administration of 500 mg of NDS-446 in Women With Dry OAB at 12 Weeks - a Single-center Study

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: 500 mg NDS-446


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years, female, ambulatory OAB symptoms > 6 months Voiding frequency > 8 times in 24 hrs and > 3 episodes of urgency (grade 3 or 4) without incontinence during 3-day diary at baseline Exclusion Criteria: Self-reported urinary incontinence (> 3 episodes in the month prior) UTI > 3 in last 12 months A diagnosis of painful bladder syndrome or interstitial cystitis LUT surgery last 6 months Drug or non-drug treatment of OAB (previous 60 days) or current meds that affect detrusor activity On Warfarin Failure to complete 3-day diary Aspirin > 81 mg daily Gross hematuria Allergy or sensitivity to aspirin Subjects taking anti-platelet agents Inability to swallow capsules

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Intervention Model: Single Group Assignment
Interventional Model Description: All participants will receive 500 mg NDS-446 daily for 12 weeks following a baseline assessment and meeting inclusion/exclusion criteria 20 premenopausal women, 20 postmenopausal women not on estrogen supplementation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intervention Group<br>All participants will receive 500 mg NDS-446 daily for 12 weeks | Drug: 500 mg NDS-446<br>* All participants will receive 500 mg NDS-446 daily for 12 weeks following a baseline assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the UG microbiota (vagina, peri-urethral, catheterized and voided urine) of female participants with urgency-frequency syndrome after 12 weeks of daily use of 500 mg of NDS-446 to the UG microbiota at baseline. | Vaginal and peri-urethral swabs, as well as voided and catheterized urine specimens, will be obtained. | 12 week visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the baseline and 12 week PPBC score in pre-menopausal and post-menopausal who take 500 mg of NDS-446 daily. | The Patient Perception of Bladder Condition (PPBC) score in the study participants. | 12 week visit |