Clinical trial NCT06124820: RCT Comparing Intravaginal Laser Therapy to Sham in Post-menopausal Women with Recurrent Urinary Tract Infections
Official title: A Single-blinded, Randomised Controlled Trial Comparing the Use of Intravaginal Laser Therapy to Sham in Post-menopausal Women with Recurrent Urinary Tract Infections (rUTI) and the Impact on the Vaginal and Urinary Microbiome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Recurrent Urinary Tract Infection
Genitourinary Syndrome of Menopause
Keywords: UTI
Recurrent Urinary Tract Infection
Genitourinary Syndrome of Menopause
Laser
CO2 Laser
Microbiome
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
First posted: 2023-11-09
Enrollment: 48
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monalisa Touch (SmartXide2 V2LR, DEKA, Florence, Italy)
Primary purpose: TREATMENT

Brief summary: Recurrent urinary tract infection (rUTI) is a common and difficult to treat problem with limited treatment option; postmenopausal women are disproportionately affected. The genitourinary syndrome of menopause (GSM) describes the broad spectrum of signs and symptoms caused by the loss of endogenous sex steroids. The combined effects of urogenital epithelial tissue thinning and changes to the vaginal and bladder microbiome can predispose to ascending UTIs. Recurrent UTIs is a component of GSM.

Intravaginal laser therapy has been shown to be safe and effective for the treatment of GSM, however, the role of laser for treatment of recurrent UTIs is unknown. We hypothesis that the incidence of UTI will be reduced as CO2 laser restores vaginal epithelium to a state similar to that of a pre-menopausal woman, preventing microtrauma, and increases Lactobacillus and normal flora (Athanasiou et al., 2016). Lactobacillus is considered the bacteria that helps keep the vagina healthy and infection free through its production of lactic acid which lowers vaginal pH, this more acidic environment may be protective from uropathogens.

We therefore aim to conduct a single-blinded, multi-centre, randomised controlled trial comparing the use of intravaginal CO2 laser therapy to sham in post-menopausal women with rUTIs and to determine the impact on the microbiome.

Detailed description: Urinary tract infections (UTIs) are the most common outpatient infection with a prevalence of 20% in women over 65, compared with 11% in the overall population (Chu and Lowder, 2018).

The genitourinary syndrome of menopause (GSM) is the accepted term used to describe the broad spectrum of genitourinary tract symptoms and signs caused by the loss of endogenous sex steroids that occurs at the time of and after the menopause. Global improvements in healthcare have resulted in an aging population. Today women are spending 40% of their lives in the postmenopausal state with 50-70% of postmenopausal women reporting symptomatic GSM. The combined effects of urogenital epithelial tissue thinning and changes to the vaginal and bladder microbiome can predispose to ascending UTIs. Recurrent UTIs is a component of GSM.

Current interventions for recurrent urinary tract infections in women include lifestyle and behavioural advice, complimentary therapies and antibiotics. These treatment regimens are not always effective or acceptable. Intravaginal Laser therapy is an alternative non-hormonal treatment of GSM as it stimulates tissue repair and restores normal vaginal function.

Currently intravaginal laser therapy has been shown to be safe and effective for the treatment of GSM, as described in a recent network analysis of 29 randomised controlled studies, incorporating 8311 patients (Li et al., 2021). Provisional results using FemTouch®, fractional CO2 laser, appear promising with 9/12 (75%) of post-menopausal women UTI free at 12 months follow-up (Yang and Foley). However, there is a scarcity of studies available looking at the impact of this novel technology for the treatment of recurrent UTIs.

The investigators aim to conduct a single-blinded, randomised controlled trial comparing the use of intravaginal CO2 laser therapy to sham in post-menopausal women with rUTIs and to determine the impact on the microbiome. The investigators hypothesise that this treatment will be effective in reducing the incidence of urinary tract infection as CO2 laser through a process of thermomodulation, simulates tissue repair by restoring vaginal epithelium to a state similar to that of a pre-menopausal woman. In addition, a study assessing the effect of micro-ablative functional CO2 laser reported an increase in Lactobacillus and normal flora (Athanasiou et al., 2016). Lactobacillus is considered the bacteria that helps keep the vagina healthy and infection free through its production of lactic acid which lowers the vaginal pH, this more acidic environment may be protective from uropathogens. The role and impact of Laser on other microbial communities is still not fully understood, this study aims to expand this knowledge base.

Recurrent UTIs is a common and difficult to treat problem with limited treatment options, this study endeavors to expand the knowledge pool and provide alternative non-pharmacological options using this novel technology.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women
* History of recurrent UTI (Defined as women who have suffered at least three episodes of symptomatic UTI within the preceding 12 months or two episodes in the last six months, or at least one episode of UTI requiring hospitalisation, or if previously prescribed prophylactic antibiotics for UTI, have completed a 3-month washout period without antibiotic prophylaxis)
* Able to give informed consent for participation in the trial
* Able and willing to adhere to a 17-month study period

Exclusion Criteria:

* Not willing to abstain from vaginal intercourse for 48 hours following laser-therapy
* Use of vaginal hormonal therapy in the three months before study start
* History of a genital fistula, a thin recto-vaginal septum as determined by the investigator or history of a fourth-degree laceration during physical screening exam (e.g., deficient perineal body)
* Active sexually transmitted disease upon vaginal exam (as determined by the investigator) that precludes treatment or any other vaginal infection
* History of lichen sclerosis
* History of radiotherapy for cervical or uterine cancer
* A medical condition that may interfere with participants' compliance with the protocol
* Women with correctable urinary tract abnormalities that are considered to be contributory to the occurrence of rUTI
* Women taking Methenamine Hippurate and unable to undergo a three-month washout period
* Undiagnosed genital bleeding
* Women who self-catheterise, or have an indwelling/suprapubic catheter
* Unable to give informed consent

Primary outcomes:
measure: To determine and compare the incidence of symptomatic antibiotic-treated UTI during the 6-month follow-up period after completion of allocated treatment
timeFrame: 6 months
Secondary outcomes:
measure: UTI history diary
timeFrame: 18 months
measure: Vaginal Health Index Score (VHIS)
timeFrame: 18 months
measure: King's Health Questionnaire (KHQ)
timeFrame: 18 months
measure: International Consultation on Incontinence Questionnaire - Female Lower Urinary Tract Symptoms (ICIQ-FLUTS)
timeFrame: 18 months
measure: International Consultation on Incontinence Questionnaire - Vaginal Symptoms (ICIQ-VS)
timeFrame: 18 months
measure: 10 cm Visual Analogue Scale for Symptoms (VAS)
timeFrame: 18 months
measure: Urinary Tract Infection Symptom Assessment Questionnaire (UTISA)
timeFrame: 18 months
measure: Female Sexual Function Index Scoring (FSFI)
timeFrame: 18 months
measure: Health Service Utilisation Questionnaire (HSU-Q)
timeFrame: 18 months
measure: Treatment satisfaction questionnaire for laser (TSQ-L)
timeFrame: 18 months
measure: Vulvoscopic Genital Tissue Appearance Scale (VGTA)
timeFrame: 18 months
measure: Adverse event recording
timeFrame: 18 months
measure: Dipstick urine analysis
timeFrame: 18 months
measure: Standard urine culture
timeFrame: 18 months
measure: Expanded Quantitative Urine Culture (EQUC)
timeFrame: 18 months
measure: 16S rRNA rapid Next-generation Gene Sequencing
timeFrame: 18 months
measure: Shotgun metagenomic sequencing
timeFrame: 18 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
References: