Clinical trial NCT04301934: Fractional CO2 Vaginal LASER Therapy for Recurrent Urinary Tract Infection
Official title: Fractional CO2 Vaginal LASER Therapy for Recurrent Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Tract Infections
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-03-10
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized controlled trial to determine clinical and microbiome difference between fractional CO2 Laser and vaginal estrogen in treating patients with recurrent urinary tract infection (UTI).

Detailed description: Recurrent urinary tract infection (rUTI) is common in postmenopausal women and can lead to significant bothersome symptoms. This clinical scenario is a difficult and common clinical problem seen by the urologist and urogynecologist with limited options for treatment. Overuse of antibiotics has led to significant resistant microorganisms and can have adverse side effects such as C. Dificile colitis. Current treatments include topical vaginal estrogen and prophylactic antibiotics. Other supplements such as cranberry pills, methenamine and D-mannose have varying levels of evidence and efficacy.

Fractional CO2 LASER vaginal therapy has recently been studied for the treatment of GSM. LASER therapy is currently commercially available and has FDA clearance for use in gynecology. Current evidence shows that with treatment, histologic changes of the vaginal epithelium have shown regeneration to a premenopausal state, along with subjective improvement in GSM symptoms and sexual function. Recent literature has shown improvements in thickening of vaginal epithelium, decreased vaginal pH and improvement in the vaginal microbiome. Based on this, the investigators propose fractional CO2 laser may have a positive impact on women with rUTI.

1. The investigators therefore hypothesize that fractional CO2 LASER vaginal therapy is non-inferior to topical vaginal estrogen therapy for the treatment of rUTI.

   a. Primary Outcome: Improvement in recurrence of culture positive UTI
2. The investigators also hypothesize that LASER therapy will improve the urinary and vaginal microbiome, decreasing the uropathogenic presence and increasing Lactobacillus.

   1. Measurement 1: The number of UTI with UPEC isolated from patients
   2. Measurement 2: The pH of the vagina as a proxy for presence of Lactobacillus sp.
   3. Measurement 3: Categorize vaginal and urinary microbial communities
3. The investigators hypothesize that LASER therapy will improve symptoms of GSM and be associated with regenerative change in vaginal histology.

   1. Measurement 1: MESA and DIVA surveys of symptoms
   2. Measurement 2: Observations of vaginal biopsy between.

Menopausal women will be recruited if subjects have recurrent UTI defined as 3 culture positive UTIs in 1 year or 2 culture positive UTIs in 6 months. Subjects will be randomized to standard of care with topical vaginal estrogen or 3 treatments of fractional CO2 LASER of the vagina. Samples will be collected to show microbiome and histologic changes with treatment.

Samples include:

Vaginal culture Urine culture vaginal biopsy (optional).

Validated questionnaires and clinical recurrence of UTI will also be gathered over 6 months.

Eligibility criteria: Inclusion Criteria:

* Female patient \>18 years old
* Postmenopausal status, documented by prior bilateral salpingo-oophorectomy, or absence of menses \>12 months
* Recurrent urinary tract infections as defined by 3 culture positive urine cultures in the last 12 months, or 2 positive urine cultures in the last 6 months.(Positive urine cultures defined by \>100K colony forming units of 1 or 2 bacterial species on clean catch sample, or \>1000 colony forming units of 1 or 2 bacterial species on sample via straight catheterization).
* Patients on vaginal estrogen must undergo a 1 month washout period prior to initiation of the trial.

Exclusion Criteria:

* Hematuria without appropriate workup
* Pelvic organ prolapse at or beyond the hymen
* Clinically relevant urinary retention
* Pelvic reconstructive surgery within 6 months
* Prior synthetic mesh procedure for pelvic organ prolapse or urinary incontinence
* Clinically relevant nephrolithiasis
* History of breast cancer
* Contraindication to topical estrogen therapy
* Anticoagulation therapy
* Prior pelvic or vaginal radiation therapy
* Prior gynecologic malignancy
* Undiagnosed genital bleeding

Primary outcomes:
measure: Prevalence of Urinary Tract Infections (UTI)
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
Study officials:
affiliation: Mayo Clinic
name: Johnny Yi, MD
role: PRINCIPAL_INVESTIGATOR
References: