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Nutraceutical Efficacy for rUTI

Primary Purpose

Urinary Tract Infections

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
D-Mannose
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Urinary Tract Infections focused on measuring UTI, recurrent UTI

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

For the RCT arms of the study, the following inclusion criteria will apply:

a. Postmenopausal women with recurrent UTI

i. Recurrent UTI defined as:

  1. ≥ 2 symptomatic, culture-proven UTI in 6 months OR

  2. ≥ 3 symptomatic, culture-proven UTI in 12 months

    ii. Postmenopausal defined as no menses for at least 12 months or surgical menopause

    b. At least one documented prior uropathogen susceptible to D-mannose

    c. Using VET for a minimum of four weeks prior to study day 1

    Inclusion criteria for the Observational arm of the study are the same with the exception of item 'c.' above (using VET for a minimum of four weeks) as participants will not be on vaginal estrogen therapy.

    Exclusion Criteria:

    For the RCT arms of the study, the exclusion criteria are as follows:

    1. Not postmenopausal
    2. Currently on daily antibiotic UTI prophylaxis (If this is the only exclusion criteria met, a woman could be cleared for inclusion in study/enrollment after a 2 week washout period occurs prior to inclusion in the study (RCT or Observational arm))
    3. Complicated UTIs (known renal tract anomaly, inability to empty bladder due to neurologic causes, performs self-catheterization or has an indwelling catheter)
    4. Patients with incomplete bladder emptying (defined as post void residual > 150 cc when minimal voided volume is >150 cc)
    5. Known contraindication to VET unless approved by patient's oncologist, oncologic surgeon, or primary care physician (History of or current endometrial cancer; History of estrogen sensitive breast cancer without approval of patient, patient's oncologist, oncologic surgeon, or primary care physician to use vaginal estrogen after counseling)
    6. History of interstitial cystitis/painful bladder syndrome
    7. Urothelial cancer
    8. Non-English speaking
    9. Enrolled in other clinical trials for UTIs
    10. Currently using D-mannose or Methenamine for UTI prevention

    Exclusion criteria for the Observational arm of the study are the same with the exception of item 'e.' above (known contraindication to VET) as participants will not be on vaginal estrogen therapy.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Experimental

Arm Label

RCT treatment arm

RCT control arm

Observational arm

Arm Description

Participants in this arm will dissolve one (1) level teaspoon of the nutraceutical powder (D-mannose) in at least 200 ml of water one time a day, approximately every 24 hours. (200 ml of water = 6.7 fluid ounces). Duration of study drug is 90 days.

Participants in this arm will not use any additional intervention.

Participants in this arm will either take a total of 1000 mg D-mannose in capsule form every 12 hours OR they will dissolve one (1) level teaspoon of the nutraceutical powder (D-mannose) in at least 200 ml of water one time a day, approximately every 24 hours. (200 ml of water = 6.7 fluid ounces). Duration of study drug is 90 days. Participants in this arm of the study have different home medications prior to study enrollment than participants in the RCT treatment arm.

Outcomes

Primary Outcome Measures

Incidence of Symptomatic, Culture Proven Urinary Tract Infections
To compare the cumulative incidence of symptomatic, culture-proven urinary tract infections in postmenopausal women with a history of rUTI on vaginal estrogen therapy randomized to receive prophylactic D-mannose versus women using vaginal estrogen therapy alone (control).

Secondary Outcome Measures

Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens
To compare the incidence of symptomatic, culture-proven urinary tract infections caused by all uropathogens potentially susceptible to D-mannose therapy in women receiving D-mannose and the control group. We will also compare these findings to the incidence of symptomatic, culture-proven urinary tract infections caused by uropathogens susceptible to D-mannose therapy in the absence of vaginal estrogen therapy (Control Arm).
Side Effects
To describe the side effects of D-mannose and determine the incidence of discontinuation of therapy due to side effects.
Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose
To compare the cumulative incidence of symptomatic, culture-proven urinary tract infections between women receiving prophylactic D-mannose treatment alongside vaginal estrogen therapy verses women receiving prophylactic D-mannose treatment whom are not on vaginal estrogen therapy (observational arm).

Full Information

First Posted
December 28, 2017
Last Updated
January 7, 2022
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03395288
Brief Title
Nutraceutical Efficacy for rUTI
Official Title
Randomized, Controlled Trial to Determine the Efficacy of Nutraceutical vs Control as Non-antibiotic Prophylaxis for Recurrent Urinary Tract Infection in Postmenopausal Women Using Vaginal Estrogen Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Performed a futility analysis and determined that study objectives could not be met.
Study Start Date
March 22, 2018 (Actual)
Primary Completion Date
April 25, 2020 (Actual)
Study Completion Date
April 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a study designed to evaluate the efficacy of a nutraceutical as a non-antibiotic treatment to prevent recurrent urinary tract infections in women that have completed menopause and are on vaginal estrogen therapy. An additional group of women with recurrent urinary tract infections that have completed menopause but are not using vaginal estrogen therapy will be followed while taking the nutraceutical. The study length is ninety days from the date that the study participant will be instructed is day 1.
Detailed Description
The objective of this study is to determine the efficacy of a nutraceutical as a non-antibiotic prophylaxis for postmenopausal women on vaginal estrogen therapy (VET) with a history of symptomatic, culture-proven recurrent urinary tract infection (rUTI) by means of a randomized, controlled trial. Recurrent urinary tract infections have a significant impact on patient health, quality of life, and finances (personal and societal). The most common uropathogen for both acute and recurrent UTIs is Escherichia coli. Historically, patients with rUTI have been placed on long-term prophylactic antibiotics to prevent recurrence. Long term antibiotic use can lead to antibiotic resistance, collateral damage to normal flora, and organ damage, such as pulmonary and hepatic toxicity with long-term nitrofurantoin use. There is an increasing prevalence of antibiotic resistance of uropathogenic E. coli and other uropathogens. Antibiotic resistance and its consequences have resulted in a need for non-antibiotic prophylaxis regimens. A growing body of literature supports the use of vaginal estrogen therapy as a first-line non-antibiotic UTI prevention strategy in postmenopausal women. While VET has been shown to significantly reduce the risk of rUTIs, some women continue to have rUTIs. Other non-antibiotic strategies have been utilized including D-mannose, a nutraceutical. Three prior studies examined D-mannose as an isolated therapy with promising results, but in our experience, a multimodal approach has often been needed. Therefore, additional studies, such as this proposed research, are needed to determine the potential additive effect of a nutraceutical as a non-antibiotic prophylaxis for postmenopausal women using vaginal estrogen therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infections
Keywords
UTI, recurrent UTI

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
There will be a RCT portion of the study with a treatment arm and a control arm and an additional observational arm of the study.
Masking
Participant
Masking Description
Participants in the RCT treatment and RCT control arm will not be told the name of the nutraceutical being studied. Participants in the observational arm will be aware of the nutraceutical being studied.
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RCT treatment arm
Arm Type
Experimental
Arm Description
Participants in this arm will dissolve one (1) level teaspoon of the nutraceutical powder (D-mannose) in at least 200 ml of water one time a day, approximately every 24 hours. (200 ml of water = 6.7 fluid ounces). Duration of study drug is 90 days.
Arm Title
RCT control arm
Arm Type
No Intervention
Arm Description
Participants in this arm will not use any additional intervention.
Arm Title
Observational arm
Arm Type
Experimental
Arm Description
Participants in this arm will either take a total of 1000 mg D-mannose in capsule form every 12 hours OR they will dissolve one (1) level teaspoon of the nutraceutical powder (D-mannose) in at least 200 ml of water one time a day, approximately every 24 hours. (200 ml of water = 6.7 fluid ounces). Duration of study drug is 90 days. Participants in this arm of the study have different home medications prior to study enrollment than participants in the RCT treatment arm.
Intervention Type
Drug
Intervention Name(s)
D-Mannose
Intervention Description
A total of 2 g D-mannose daily
Primary Outcome Measure Information:
Title
Incidence of Symptomatic, Culture Proven Urinary Tract Infections
Description
To compare the cumulative incidence of symptomatic, culture-proven urinary tract infections in postmenopausal women with a history of rUTI on vaginal estrogen therapy randomized to receive prophylactic D-mannose versus women using vaginal estrogen therapy alone (control).
Time Frame
each participant will be followed for 90 days during study enrollment
Secondary Outcome Measure Information:
Title
Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens
Description
To compare the incidence of symptomatic, culture-proven urinary tract infections caused by all uropathogens potentially susceptible to D-mannose therapy in women receiving D-mannose and the control group. We will also compare these findings to the incidence of symptomatic, culture-proven urinary tract infections caused by uropathogens susceptible to D-mannose therapy in the absence of vaginal estrogen therapy (Control Arm).
Time Frame
each participant will be followed for 90 days during study enrollment
Title
Side Effects
Description
To describe the side effects of D-mannose and determine the incidence of discontinuation of therapy due to side effects.
Time Frame
each participant will be followed for 90 days during study enrollment
Title
Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose
Description
To compare the cumulative incidence of symptomatic, culture-proven urinary tract infections between women receiving prophylactic D-mannose treatment alongside vaginal estrogen therapy verses women receiving prophylactic D-mannose treatment whom are not on vaginal estrogen therapy (observational arm).
Time Frame
each participant will be followed for 90 days during study enrollment

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
This study will involve only adult, postmenopausal women as recurrent UTI predominantly affect this population. Recurrent UTI in men would be considered complicated and would not be addressed with a prophylactic treatment like d-mannose.In addition, men do not go through menopause and do not have a vagina and would thus not be treated with vaginal estrogen therapy.
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For the RCT arms of the study, the following inclusion criteria will apply: a. Postmenopausal women with recurrent UTI i. Recurrent UTI defined as: ≥ 2 symptomatic, culture-proven UTI in 6 months OR ≥ 3 symptomatic, culture-proven UTI in 12 months ii. Postmenopausal defined as no menses for at least 12 months or surgical menopause b. At least one documented prior uropathogen susceptible to D-mannose c. Using VET for a minimum of four weeks prior to study day 1 Inclusion criteria for the Observational arm of the study are the same with the exception of item 'c.' above (using VET for a minimum of four weeks) as participants will not be on vaginal estrogen therapy. Exclusion Criteria: For the RCT arms of the study, the exclusion criteria are as follows: Not postmenopausal Currently on daily antibiotic UTI prophylaxis (If this is the only exclusion criteria met, a woman could be cleared for inclusion in study/enrollment after a 2 week washout period occurs prior to inclusion in the study (RCT or Observational arm)) Complicated UTIs (known renal tract anomaly, inability to empty bladder due to neurologic causes, performs self-catheterization or has an indwelling catheter) Patients with incomplete bladder emptying (defined as post void residual > 150 cc when minimal voided volume is >150 cc) Known contraindication to VET unless approved by patient's oncologist, oncologic surgeon, or primary care physician (History of or current endometrial cancer; History of estrogen sensitive breast cancer without approval of patient, patient's oncologist, oncologic surgeon, or primary care physician to use vaginal estrogen after counseling) History of interstitial cystitis/painful bladder syndrome Urothelial cancer Non-English speaking Enrolled in other clinical trials for UTIs Currently using D-mannose or Methenamine for UTI prevention Exclusion criteria for the Observational arm of the study are the same with the exception of item 'e.' above (known contraindication to VET) as participants will not be on vaginal estrogen therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerry Lowder, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share individual participant data
Citations:
PubMed Identifier
35421017
Citation
Lenger SM, Chu CM, Ghetti C, Durkin MJ, Jennings Z, Sutcliffe S, Lowder JL. Feasibility and Research Insights From a Randomized Controlled Trial for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen Therapy. Female Pelvic Med Reconstr Surg. 2022 Jun 1;28(6):e163-e170. doi: 10.1097/SPV.0000000000001171.
Results Reference
derived

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Nutraceutical Efficacy for rUTI

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