Fractional CO2 Vaginal LASER Therapy for Recurrent Urinary Tract Infection

• ClinicalTrials.gov Identifier: NCT04301934
• Recruitment Status: Recruiting
• First Posted: March 10, 2020
• Last Update Posted: February 13, 2023
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Johnny Yi, Mayo Clinic

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Urinary Tract Infections	Device: Mona Lisa Touch; Drug: Conjugated estrogen; Drug: Estradiol	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Fractional CO2 Vaginal LASER Therapy for Recurrent Urinary Tract Infection
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Vaginal Estrogen Therapy Group; Women randomized to vaginal estrogen therapy will be offered vaginal cream conjugated estrogen (Premarin) 0.5 gm per vaginal twice weekly or estradiol (Estrace): 1gm per vaginal twice weekly	Drug: Conjugated estrogen; Current standard treatment for recurrent UTIs in postmenopausal women; Other Name: Premarin; Drug: Estradiol; Current standard treatment for recurrent UTIs in postmenopausal women; Other Name: Estrace
Experimental: Laser Therapy Group; Women randomized to the laser therapy group will undergo 3 treatments, 6 weeks apart.	Device: Mona Lisa Touch; Fractional CO2 LASER

Outcome Measures

Primary Outcome Measures :

1. Improvement in recurrence of culture positive urinary tract infections [ Time Frame: 6 months ]
   Number of culture positive, symptomatic urinary tract infections in women

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic in Arizona; Recruiting

Phoenix, Arizona, United States, 85054

Contact: Arleth Valencia 480-342-6487 Valencia.Arleth@mayo.edu

Sponsors and Collaborators

Mayo Clinic

Investigators

• Principal Investigator: Johnny Yi, MD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Johnny Yi, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04301934
• Other Study ID Numbers: 18-002297
• First Posted: March 10, 2020
• Last Update Posted: February 13, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Infections; Communicable Diseases; Urinary Tract Infections; Disease Attributes; Pathologic Processes; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Estradiol; Estrogens; Estrogens, Conjugated (USP); Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs