American Cranberries to Prevent UTIs in Susceptible Women

• ClinicalTrials.gov Identifier: NCT04626362
• Recruitment Status: Recruiting
• First Posted: November 12, 2020
• Last Update Posted: December 5, 2023
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

The investigators pre-preliminary study showed that the urine from a portion of study participants had anti-adhesion activity. The investigators propose that UTI susceptible women can be divided into responders and non-responders depending on whether cranberry intake increase anti-adhesion activity of their urine. The overall objectives are to identify gut microbes and anti-adhesive urinary biomarkers which significantly contribute to the anti-adhesion of E. coli.

Condition or disease	Intervention/treatment	Phase
Healthy	Other: Cranberry juice; Other: Placebo juice	Not Applicable

Detailed Description:

The American cranberries (Vaccinium macrocarpon) have been consumed for centuries to prevent urinary tract infections (UTI), which affect 50% of women in their lifetime. However, NIH-funded clinical trials of cranberries on UTI in the last 20 years yielded conflicting results but the reasons are unknown. About 90% of UTI are initiated by adhesion of uropathogenic E. coli on urinary tract epithelia. It was reported that human urine after cranberry intake inhibited the adhesion of E. coli. A-type procyanidins and xyloglucans are the presumed bioactives in cranberries; however, none of these compounds are absorbable in small intestine. They are degraded by microbes in colon.The pre-preliminary study showed that the urine from a portion of study participants had anti-adhesion activity, suggesting there are polymorphisms in human's ability to metabolize cranberry bioactives. Based on these observations, the investigators formulate a novel hypothesis that not all, but a fraction of women harbor specific gut microbes with the ability to catabolize cranberry bioactives to anti-adhesion metabolites in the urine; therefore, the variation of gut microbiome is the underlying mechanism for metabolic polymorphisms and disparity in UTI prevention. The investigators propose that UTI susceptible women can be divided into responders and non-responders depending on whether cranberry intake increase anti-adhesion activity of their urine. The overall objectives are to identify gut microbes and anti-adhesive urinary biomarkers which significantly contribute to the anti-adhesion of E. coli. The expected result will be to generate strong preliminary data showing the differences of gut microbiome between responders and non-responders in additional to correlations between gut microbes and candidate anti-adhesion biomarkers in the urine of UTI susceptible women.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Experimental: Cranberry juice consumption participants will be provided cranberry juice to consume for 21 days Intervention: Other: Cranberry juice Placebo Comparator: Placebo juice consumption participants will be provided placebo juice to consume for 21 days Intervention: Other: Placebo juice
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: To Determine the Metabolic Polymorphisms of American Cranberries to Prevent UTIs in Susceptible Women Using an Integrated Metabolome-Microbiome Approach
• Actual Study Start Date: February 2, 2021
• Estimated Primary Completion Date: August 20, 2025
• Estimated Study Completion Date: August 20, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental: Cranberry juice consumption; Participants will be provided cranberry juice to consume for 21 days	Other: Cranberry juice; Cranberry juice cocktail will be provided by Ocean Spray Cranberries, Inc.
Experimental: Placebo juice consumption; Participants will be provided placebo juice to consume for 21 days	Other: Placebo juice; Apple juice added with flavor and colorants will be provided by Ocean Spray Cranberries, Inc.

Outcome Measures

Primary Outcome Measures :

1. Change in the anti-adhesion activity [ Time Frame: Baseline and 21 days of each intervention ]
   Compare the statistical difference between the changes from baseline in the an-adhesion activity uropathogenic E. coli in UTI-susceptible women after consuming the cranberry beverage for 3 weeks versus the change after consuming the control beverage for 3 weeks. Anti-adhesion activity in urine will be measured using a fluoresces-based micro-plate method. The anti-adhesion activities of urines will be expressed by its equivalence to myricetin level. The unit for urine anti-adhesion activities is µg myricetin/ mg creatinine.

Secondary Outcome Measures :

1. Change in urinary biomarkers [ Time Frame: Baseline and 21 days of each intervention ]
   Compare the statistical difference between the change from baseline in the an-adhesion activity uropathogenic E. coli in UTI-susceptible women after consuming the cranberry beverage for 3 weeks versus the change after consuming the control beverage for 3 weeks. The Urinary biomarkers will be identified and measured using LC-Orbitrap-MS.
2. Change in gut microbiomes [ Time Frame: Baseline and 21 days of each intervention ]
   Compare the difference between the changes in gut microbiomes between responders and non-responders participants after consuming the cranberry beverage for 3 weeks versus the change after consuming the control beverage for 3 weeks. The gut microbiomes will be measured Genomic microbial DNA the extraction of genomic microbial DNA from fecal samples using DNA isolation kits and the 16S ribosomal RNA gene (V1-3 region) will be amplified and sequenced.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: This study will determine American cranberries to prevent urinary tract infections (UTIs) in susceptible women.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy women participants
• BMI 18.5-29.9 kg/m2
• At least 110 pounds in weight

Exclusion Criteria:

• BMI≥ 30 kg/m2
• Pregnancy and breast-feeding
• Smoking, frequent alcohol use
• History of any clinically important disorder that may interfere with interpretation of the results,
• Intake of medication that might influence the outcome of the study

Contacts and Locations

Contacts

Contact: Liwei Gu, PhD; (352)2943730; lgu@ufl.edu

Contact: Yavuz Yagiz, PhD; (352)2943988; yavuzy@ufl.edu

Locations

United States, Florida

Food Science and human nutrition department at University of Florida; Recruiting

Gainesville, Florida, United States, 32611

Contact: Yavuz Yagiz, PhD

Sponsors and Collaborators

University of Florida

Investigators

• Principal Investigator: Liwei Gu, PhD; University of Florida
• Study Director: Yavuz Yagiz, PhD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT04626362
• Other Study ID Numbers: IRB202002624
• First Posted: November 12, 2020
• Last Update Posted: December 5, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:

Cranberry; UTI