Urinary Tract InfectionsPhase 2/3NCT03395288
Nutraceutical Efficacy for rUTI
A Phase 2/3 study testing D-Mannose in people with Urinary Tract Infections, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Urinary Tract Infections
- What is being tested?
- D-Mannose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Mar 2018to 25 Apr 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For the RCT arms of the study, the following inclusion criteria will apply:
- Postmenopausal women with recurrent UTI
- Recurrent UTI defined as:
- ≥ 2 symptomatic, culture-proven UTI in 6 months OR
- ≥ 3 symptomatic, culture-proven UTI in 12 months
- Postmenopausal defined as no menses for at least 12 months or surgical menopause
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- At least one documented prior uropathogen susceptible to D-mannose
- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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
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.
Read the 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.
- Conditions
- Urinary Tract Infections
- Being tested
- D-Mannose
- Keywords
- UTI, recurrent UTI
- Medical subject headings
- Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-MannoseDrug
A total of 2 g D-mannose daily
| Study group | Role | What they receive |
|---|---|---|
| RCT treatment arm | Experimental | 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. Receives: Drug: D-Mannose |
| RCT control arm | No intervention | Participants in this arm will not use any additional intervention. |
| Observational arm | Experimental | 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. Receives: Drug: D-Mannose |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: each participant will be followed for 90 days during study enrollment
Secondary outcomes (3)
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).
Measured: 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.
Measured: 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).
Measured: each participant will be followed for 90 days during study enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2018
- Study start22 Mar 2018
- Primary completion25 Apr 2020
- Study completion25 Apr 2020
Why it stopped: Performed a futility analysis and determined that study objectives could not be met.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jerry Lowder, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03395288
- Sponsor's protocol ID
- 201711120
- Status last verified
- Jan 2022
- First submitted
- 28 Dec 2017
- Last updated
- 4 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual participant data
Publications
Lenger SM, Chu CM, Ghetti C, Durkin MJ, Jennings Z, Wan F, Sutcliffe S, Lowder JL. d-Mannose for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen: A Randomized Controlled Trial. Urogynecology (Phila). 2023 Mar 1;29(3):367-377. doi: 10.1097/SPV.0000000000001270. Epub 2022 Oct 15.
PubMed 36808931Lenger 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.
PubMed 35421017
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03395288
- Acronym / sponsor ID
- 201711120
- Conditions
- Urinary Tract Infections
- Keywords
- UTI, recurrent UTI
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Performed a futility analysis and determined that study objectives could not be met.
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 22 Mar 2018 (actual)
- Primary completion
- 25 Apr 2020 (actual)
- Study completion
- 25 Apr 2020 (actual)
- First posted
- 10 Jan 2018 (actual)
- Results
- Posted 4 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| RCT treatment arm | Experimental | Drug: D-MannoseParticipants 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. |
| RCT control arm | No intervention | –Participants in this arm will not use any additional intervention. |
| Observational arm | Experimental | Drug: D-MannoseParticipants 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Postmenopausal women with recurrent UTI
- Recurrent UTI defined as:
- ≥ 2 symptomatic, culture-proven UTI in 6 months OR
- ≥ 3 symptomatic, culture-proven UTI in 12 months
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-MannoseA total of 2 g D-mannose daily | Drug | Observational arm, RCT treatment arm |
Primary outcome
Incidence of Symptomatic, Culture Proven Urinary Tract Infections
Time frame: 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).
3 secondary outcomes
Incidence of Symptomatic Culture Proved UTI From D-mannose Susceptible Uropathogens
Time frame: each participant will be followed for 90 days during study enrollment
Side Effects
Time frame: each participant will be followed for 90 days during study enrollment
Incidence of Symptomatic, Culture Proven UTI in All Participants Taking D-mannose
Time frame: each participant will be followed for 90 days during study enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36808931Lenger SM, Chu CM, Ghetti C, Durkin MJ, Jennings Z, Wan F, Sutcliffe S, Lowder JL. d-Mannose for Recurrent Urinary Tract Infection Prevention in Postmenopausal Women Using Vaginal Estrogen: A Randomized Controlled Trial. Urogynecology (Phila). 2023 Mar 1;29(3):367-377. doi: 10.1097/SPV.0000000000001270. Epub 2022 Oct 15.
- Derived from this study: PubMed 35421017Lenger 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.
- Individual participant dataSharing planned: No. There is no plan to share individual participant data
Related trials for Urinary Tract Infections
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Probiotic Supplement for Recurrent UTIs in Healthy Women (L. Plantarum, L. Rhamnosus, B. Lactis)
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Active, not recruitingObservational study
The Impact of De-implementing Urine Dipsticks for Diagnosis of UTIs in Hospitals
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Precision Management of Urinary Tract Symptoms in Older Women
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VA Quality Enhancement Research Initiative (QUERI) CARRIAGE VAST
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Prediction and Prevention of Bloodstream Infections After Kidney Transplantation
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jerry Lowder, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing D-Mannose in people with Urinary Tract Infections, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Symptomatic, Culture Proven Urinary Tract Infections (time frame: each participant will be followed for 90 days during study enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03395288, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2022.