Urinary Tract Infections
Conditions
Keywords
UTI, recurrent UTI
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.
Interventions
DRUGD-Mannose
A total of 2 g D-mannose daily
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
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.
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.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Symptomatic, Culture Proven Urinary Tract Infections | each participant will be followed for 90 days during study enrollment | 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens | each participant will be followed for 90 days during study enrollment | 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 | each participant will be followed for 90 days during study enrollment | 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 | each participant will be followed for 90 days during study enrollment | 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). |
Countries
United States
Participant flow
Pre-assignment details
Of the 61 patients consented, 4 patients were in the observational arm and 57 were in the RCT arm (28 treatment, 29 control).
Participants by arm
| Arm | Count |
|---|---|
| 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.
D-Mannose: A total of 2 g D-mannose daily | 28 |
| RCT Control Arm Participants in this arm will not use any additional intervention. | 29 |
| 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.
D-Mannose: A total of 2 g D-mannose daily | 4 |
| Total | 61 |
Baseline characteristics
| Characteristic | RCT Treatment Arm | RCT Control Arm | Observational Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 16 Participants | 3 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 13 Participants | 1 Participants | 23 Participants |
| Age, Continuous | 70.7 years | 67.4 years | 71.5 years | 69.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 28 Participants | 4 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 28 Participants | 4 Participants | 58 Participants |
| Region of Enrollment United States | 28 participants | 29 participants | 4 participants | 61 participants |
| Sex: Female, Male Female | 28 Participants | 29 Participants | 4 Participants | 61 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 29 | 0 / 4 |
| other Total, other adverse events | 14 / 27 | 16 / 29 | 2 / 4 |
| serious Total, serious adverse events | 0 / 27 | 0 / 29 | 0 / 4 |
Outcome results
Primary
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).
Time frame: each participant will be followed for 90 days during study enrollment
Population: 57 patients were enrolled in the RCT(28 randomized to the treatment arm , 29 to the control arm). 4 participants in the Observational Arm. A total of 44 patients started study day1 across all three groups. Data was analyzed for 19 patients in the treatment arm and 25 patients in the control arm. Due to early termination and low recruitment in the Observational Arm, data on the 4 participants was not analyzed (1 withdrew prior to study day 1, 1 withdrew prior to completion - not study related).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RCT Treatment Arm | Incidence of Symptomatic, Culture Proven Urinary Tract Infections | 6 Participants |
| RCT Control Arm | Incidence of Symptomatic, Culture Proven Urinary Tract Infections | 12 Participants |
| Observational Arm | Incidence of Symptomatic, Culture Proven Urinary Tract Infections | 1 Participants |
Secondary
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).
Time frame: each participant will be followed for 90 days during study enrollment
Population: There were 57 patients enrolled in the RCT (28 randomized to the treatment arm and 29 randomized to the control arm). There were 4 participants in the observational arm (data for 2 available for informal analysis; 1 withdrew prior to study day 1; 1 withdrew week 3 not related to study drug0. A total of 44 patients started study day 1 across all three groups. Data was analyzed for 19 patients in the treatment arm and 25 patients in the control arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RCT Treatment Arm | Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens | 6 Participants |
| RCT Control Arm | Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens | 10 Participants |
| Observational Arm | Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens | 1 Participants |
Secondary
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).
Time frame: each participant will be followed for 90 days during study enrollment
Population: There were 57 patients enrolled in the RCT (28 randomized to the treatment arm and 29 randomized to the control arm). There were 4 participants in the observational arm. A total of 44 patients started study day 1 across all three groups. Data was analyzed for 19 patients in the treatment arm and 25 patients in the control arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RCT Treatment Arm | Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose | 6 Participants |
| RCT Control Arm | Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose | 12 Participants |
| Observational Arm | Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose | 1 Participants |
Secondary
Side Effects
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
Population: There were 57 patients enrolled in the RCT (28 randomized to the treatment arm and 29 randomized to the control arm). There were 4 participants in the observational arm. A total of 44 patients started study day 1 across all three groups. Data was analyzed for 19 patients in the treatment arm and 25 patients in the control arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RCT Treatment Arm | Side Effects | 3 Participants |
| RCT Control Arm | Side Effects | 0 Participants |
| Observational Arm | Side Effects | 0 Participants |