Preventing Recurrent UTI With Vaginal Estrogen (PRUVE)
Primary Purpose
Recurrent Urinary Tract Infection, Urinary Tract Infections, Cystitis Recurrent
Status
Enrolling by invitation
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Vaginal estradiol tablets
Sponsored by
About this trial
This is an interventional prevention trial for Recurrent Urinary Tract Infection focused on measuring women
Eligibility Criteria
Inclusion Criteria:
Participants in this study will be
- Postmenopausal women (menopausal for at least 1 year)
- Minimum age of 55 years
Participants will have documentation of recurrent UTI, defined as follows:
- History of treatment for at least 3 UTIs in the past year or 2 episodes within 6 months AND
- At least one positive urine culture during an acute symptomatic episode.
Exclusion Criteria:
- Women receiving antibiotic prophylaxis to prevent UTI recurrence;
- Women with contraindications to vaginal estrogen (as indicated on the FDA-mandated package insert) and those who have used vaginal or systemic estrogen within the past 6 months;
- Women with an active UTI and those who have received antibiotics within the prior 2 weeks;
- Women with complicated rUTI, defined by immune compromise, anatomic or functional abnormalities of the urinary tract, indwelling catheterization, those performing self-catheterization, and those with neurological disease or illness relevant to the lower urinary tract;
- Women with only asymptomatic bacteriuria (rather than recurrent symptomatic UTI)
Sites / Locations
- Johns Hopkins Bayview Medical Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Vaginal estrogen therapy
Arm Description
Participants receive Vaginal estrogen therapy.
Outcomes
Primary Outcome Measures
Change in Vaginal microbiota
Changes to relative vaginal abundance of key Lactobacillus spp. before and after treatment.
Change in Vaginal Interleukin-6 level
Changes to vaginal Interleukin-6 before and after treatment.
Change in Urinary microbiota
Changes to relative urinary abundance of key Lactobacillus spp. before and after treatment.
Change in Urinary Interleukin-6 level
Changes to urinary Interleukin-6 before and after treatment.
Secondary Outcome Measures
Urinary tract infection recurrence
Occurrence of symptomatic UTI after at least 12 weeks of therapy.
Full Information
NCT ID
NCT05551949
First Posted
September 20, 2022
Last Updated
October 17, 2023
Sponsor
Johns Hopkins University
Collaborators
University of Maryland, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT05551949
Brief Title
Preventing Recurrent UTI With Vaginal Estrogen
Acronym
PRUVE
Official Title
Mechanisms of Successful Vaginal Estrogen Prophylaxis for Postmenopausal Women With Recurrent Urinary Tract Infections: Urogenital Microbiota and Host Immune Responses
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
January 31, 2023 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
University of Maryland, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
Among postmenopausal women who suffer from recurrent urinary tract infections (UTI), vaginal estrogen therapy prevents UTI recurrences for 50% of sufferers. This research will investigate why some women benefit but others do not, focusing on (a) the effects of vaginal estrogen therapy on the bacteria that inhabit the vagina and bladder, (b) its influence on immune responses in both compartments, and (c) the extent to which those changes are critical to successful UTI prevention. The findings will be a first step in the development of more effective strategies to prevent UTI, one of the most common and costly benign urologic conditions.
Detailed Description
Recurrent urinary tract infections (rUTI) are a significant problem among older women: 13% of female Medicare beneficiaries experience at least one UTI annually and >40% of these develop chronic recurrent UTI. Although UTIs are significantly reduced by vaginal estrogen therapy (VET), 50% of those using VET continue to experience UTI recurrences. It is unknown why some women benefit from VET while others do not. This application focuses on interrogating two mechanisms likely to be central to the effectiveness of VET. The first is the urogenital microbiota: an increase in vaginal lactobacilli is the purported mechanism by which VET reduces rUTI. Important and unanswered questions include how VET influences specific Lactobacillus spp., whether changes to specific Lactobacillus spp are the key to successful prophylaxis, and how VET affects the urinary microbiota. A second mechanism addressed by this application is the host vaginal and urinary immune response. Estrogen appears to influence localized urogenital immune responses, including Th17 and Th1 versus Th2 pathway signaling. Animal studies suggest that these compartmentalized immune responses play a critical role in UTI susceptibility, but human data are lacking. This application will address these unanswered questions. Postmenopausal women with rUTI will be treated with VET. Samples collected before and after VET will characterize vaginal and urinary microbiota, soluble mediators of inflammation in both compartments, and vaginal D-lactic acid. Aims 1 and 2 of this proposal will investigate the impact of VET on the urogenital microbiota and urogenital immune responses, respectively. Aim 3 will characterize the urogenital environments of participants who continue to experience rUTI during VET versus those who remain UTI-free. The accomplishment of these aims will provide pilot data for a larger and more definitive clinical trial. These proposed studies are a key step toward the investigators' goals of identifying biomarkers that reliably predict a successful response to rUTI prophylaxis and ascertaining the biological conditions required for successful UTI prevention. Ultimately, an understanding of the mechanisms of rUTI prevention will allow the development of novel and effective prevention strategies for postmenopausal women suffering from rUTI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Urinary Tract Infection, Urinary Tract Infections, Cystitis Recurrent
Keywords
women
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Open label, single group clinical trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vaginal estrogen therapy
Arm Type
Other
Arm Description
Participants receive Vaginal estrogen therapy.
Intervention Type
Drug
Intervention Name(s)
Vaginal estradiol tablets
Intervention Description
Vaginal estradiol tablets (10mcg).
Primary Outcome Measure Information:
Title
Change in Vaginal microbiota
Description
Changes to relative vaginal abundance of key Lactobacillus spp. before and after treatment.
Time Frame
Baseline and 12 weeks
Title
Change in Vaginal Interleukin-6 level
Description
Changes to vaginal Interleukin-6 before and after treatment.
Time Frame
Baseline and 12 weeks
Title
Change in Urinary microbiota
Description
Changes to relative urinary abundance of key Lactobacillus spp. before and after treatment.
Time Frame
Baseline and 12 weeks
Title
Change in Urinary Interleukin-6 level
Description
Changes to urinary Interleukin-6 before and after treatment.
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Urinary tract infection recurrence
Description
Occurrence of symptomatic UTI after at least 12 weeks of therapy.
Time Frame
Weeks 12 to 24
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
identify as female
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants in this study will be
Postmenopausal women (menopausal for at least 1 year)
Minimum age of 55 years
Participants will have documentation of recurrent UTI, defined as follows:
History of treatment for at least 3 UTIs in the past year or 2 episodes within 6 months AND
At least one positive urine culture during an acute symptomatic episode.
Exclusion Criteria:
Women receiving antibiotic prophylaxis to prevent UTI recurrence;
Women with contraindications to vaginal estrogen (as indicated on the FDA-mandated package insert) and those who have used vaginal or systemic estrogen within the past 6 months;
Women with an active UTI and those who have received antibiotics within the prior 2 weeks;
Women with complicated rUTI, defined by immune compromise, anatomic or functional abnormalities of the urinary tract, indwelling catheterization, those performing self-catheterization, and those with neurological disease or illness relevant to the lower urinary tract;
Women with only asymptomatic bacteriuria (rather than recurrent symptomatic UTI)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Victoria Handa, MD MHS
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be shared after study completion
IPD Sharing Time Frame
Data sharing will be provided within one year of study conclusion.
IPD Sharing Access Criteria
To be determined
Learn more about this trial
Preventing Recurrent UTI With Vaginal Estrogen
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