Nutraceutical Efficacy for rUTI

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

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.

Study Overview

• Status: Terminated
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: D-Mannose

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RCT treatment arm; 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.	Drug: D-Mannose; A total of 2 g D-mannose daily
No Intervention: RCT control arm; Participants in this arm will not use any additional intervention.
Experimental: Observational arm; 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.	Drug: D-Mannose; A total of 2 g D-mannose daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	each participant will be followed for 90 days during study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	each participant will be followed for 90 days during study enrollment
Side Effects	To describe the side effects of D-mannose and determine the incidence of discontinuation of therapy due to side effects.	each participant will be followed for 90 days during study enrollment
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).	each participant will be followed for 90 days during study enrollment

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Jerry Lowder, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): April 25, 2020
• Study Completion (Actual): April 25, 2020

Study Registration Dates

• First Submitted: December 28, 2017
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: UTI; recurrent UTI
• Additional Relevant MeSH Terms: Urologic Diseases; Infections; Urinary Tract Infections
• Other Study ID Numbers: 201711120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to share individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No