Clinical trial NCT03395288: 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
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Urinary Tract Infections
Keywords: UTI
recurrent UTI
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2018-01-10
Enrollment: 61
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

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.

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:

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.

Primary outcomes:
measure: Incidence of Symptomatic, Culture Proven Urinary Tract Infections
timeFrame: each participant will be followed for 90 days during study enrollment
Secondary outcomes:
measure: Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens
timeFrame: each participant will be followed for 90 days during study enrollment
measure: Side Effects
timeFrame: each participant will be followed for 90 days during study enrollment
measure: Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose
timeFrame: each participant will be followed for 90 days during study enrollment
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jerry Lowder, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.