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

Overactive Bladder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05557279
• Other study ID #: 215838
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: December 2023
• Source: Loyola University
• Contact: Mary Tulke, RN
• Phone: 708-216-2186
• Email: mtulke[@]luc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Overactive Bladder
• Urinary Bladder, Overactive

Intervention

Drug:
• 500 mg NDS-446
All participants will receive 500 mg NDS-446 daily for 12 weeks following a baseline assessment

Locations

Country	Name	City	State
United States	Loyola Medical Center	Maywood	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Loyola University

Country where clinical trial is conducted

United States, 

References & Publications (27)

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Cho A, Eidelberg A, Butler DJ, Danko D, Afshinnekoo E, Mason CE, Chughtai B. Efficacy of Daily Intake of Dried Cranberry 500 mg in Women with Overactive Bladder: A Randomized, Double-Blind, Placebo Controlled Study. J Urol. 2021 Feb;205(2):507-513. doi: 1 — View Citation

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Price TK, Dune T, Hilt EE, Thomas-White KJ, Kliethermes S, Brincat C, Brubaker L, Wolfe AJ, Mueller ER, Schreckenberger PC. The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms. J Clin Microbiol. 2016 May — View Citation

Price TK, Wolff B, Halverson T, Limeira R, Brubaker L, Dong Q, Mueller ER, Wolfe AJ. Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota. mBio. 2020 Apr 21;11(2):e00475-20. doi: 10.1128/mBio.00475-20. — View Citation

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Thomas-White K, Taege S, Limeira R, Brincat C, Joyce C, Hilt EE, Mac-Daniel L, Radek KA, Brubaker L, Mueller ER, Wolfe AJ. Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder sym — View Citation

Thomas-White KJ, Hilt EE, Fok C, Pearce MM, Mueller ER, Kliethermes S, Jacobs K, Zilliox MJ, Brincat C, Price TK, Kuffel G, Schreckenberger P, Gai X, Brubaker L, Wolfe AJ. Incontinence medication response relates to the female urinary microbiota. Int Urog — View Citation

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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