A Single-Blind, Randomized Study to Compare fCO2 Laser Therapy Versus Sham for Treatment of SUI in Women

Study Overview
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Brief Summary
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This is a prospective randomized sham-controlled study of patients undergoing vaginal treatment with a fractional carbon dioxide (fCO2) laser for stress urinary incontinence (SUI) symptoms. Eligible participants will be randomized (like a flip of a coin) to receive active or sham fCO2 laser treatments. Three treatments with the fCO2 laser or sham to the vagina will be performed, approximately four weeks apart.

Detailed Description
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Stress urinary incontinence (SUI) is a common problem that affects 35-40% of women worldwide. SUI occurs when a woman experiences involuntary leakage of urine with physical activities such as exercise, coughing and sneezing that increases intra-abdominal pressure. Vaginal laser therapy offers a potential novel treatment for SUI, however there is limited scientific evidence to show benefits to treatment. A sham controlled study will further add to the literature and evidence to support or oppose the use of the fCO2 laser for SUI. The purpose of this study is to compare active therapy to sham treatment to determine if a true benefit to treatment exists. Eligible participants will be randomized 1:1, to receive active or sham fCO2 laser treatments. Three treatments, active or sham, to the vagina will be performed approximately four weeks apart. The primary efficacy endpoint is four weeks after completing all treatments. Treatment durability and safety will be assessed eight weeks after the primary endpoint.

Official Title
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A Single-Blind, Randomized Study to Compare the Efficacy and Safety of Fractional Carbon Dioxide Laser Therapy Versus Sham for Treatment of Stress Urinary Incontinence Symptoms in Women

Conditions
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Stress Urinary Incontinence, Urinary Incontinence

Intervention / Treatment
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* Device: Active fCO2 laser treatment
* Device: Sham fCO2 laser treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age ≥18 years and ≤75 of age Mild to moderate SUI defined by Stamey Grade 1 and 2 Positive bladder stress test at screening Negative urinary tract infection (UTI) at the time of study enrollment. If a patient does have a UTI, they may be rescreened after treatment No additional SUI therapy in the past 2 months such as pelvic floor physical therapy, medications, or participation in another SUI study No prior history of midurethral sling or fascial sling for SUI No prior history of urethral bulking procedure for SUI No prior history of autologous muscle derived stem cell injection in the urethra Must sign the informed consent form Must be willing to comply with the study protocol Exclusion Criteria: Contraindications to fCO2 laser treatment, such as: previous pelvic mesh surgery current or previous genital cancers, radiation to the vaginal or colo-rectal tissue, currently pregnant or less than 3 months following pregnancy active infections (candidiasis, herpes genitalis, etc.) vaginal or cervical lesions noted on initial exam Patients with undiagnosed vaginal bleeding not related to menses Active vulvar or vaginal infection, including herpes Current UTI, confirmed by positive urine culture and patient-reported UTI symptoms Recurrent UTI defined as 3 UTIs in the past 6 months or 4 UTIs in the past 1 year Pelvic or vaginal surgery within the past 9 months Pelvic organ prolapse beyond the introitus Patient possesses any other characteristics that, per the investigator's judgment, deems them unsuitable (i.e. may increase patient's risk, may affect the conduct of the study, etc.) for the treatment and/or study. Participation in an investigational trial that used a study treatment, medication and/or biologic within 30 days or less prior to the date of the screening visit. Deferral Patients may be deferred and rescreened at a later date under the following conditions: Patients with active vulvar or vaginal infections may be rescreened after treatment Patients with an active UTI may be rescreened after treatment Patients with undiagnosed vaginal bleeding may be rescreened after complete work-up, treatment and resolution of vaginal bleeding Patients pregnant within the past 3 months Patients with recent vaginal or uterine surgery within the 9 months Note: To preserve the scientific integrity of the study some inclusion and exclusion criteria are not listed. At the conclusion of the study all items will be posted.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized 1:1 to active fCO2 laser therapy or sham. Study will be performed in a single-blind manner. (Participant and biostatistician)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active fCO2 laser treatment<br>Laser probe will be inserted into the vagina. The laser treatment is delivered at 6 points to the vaginal wall. Delivery begins at the most proximal and the wand is retracted by 1 cm and another row of laser treatment is delivered. The number of levels is determined by vaginal length. | Device: Active fCO2 laser treatment<br>* The laser probe is inserted into the vagina. Laser treatment is delivered at 6 points at each level of the vaginal wall (12, 2, 4, 6, and 10 o'clock positions). Delivery begins at the most proximal and the probe is retracted by 1 cm and another row of laser treatments are delivered. The number of levels is determined by the patient's vaginal length.<br>|
| Sham Comparator: Sham fCO2 laser treatment<br>Laser probe will be inserted into the vagina. To prevent the delivery of laser energy, the laser will remain in standby mode during the visit. Keeping the laser in standby mode prevents laser exposure. The treatment will appear to be the same as the active treatment. The machine maintains a low humming noise while in standby mode. | Device: Sham fCO2 laser treatment<br>* The laser probe is inserted into the vagina. The laser will remain in standby mode during the treatment preventing laser exposure. The treatment will appear to be the same as the active treatment with the probe starting at the most proximal and following the same 6 points of treatment delivery. The probe is retracted in the same manner and another row of treatment is simulated. The machine maintains a low humming noise while in standby mode. No active laser treatment is delivered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of fCO2 laser therapy in women with mild to moderate SUI symptoms compared to sham by evaluating the responder rate. | A patient is called a responder if there is a greater than or equal to 50% reduction from baseline in the number of subject-reported SUI episodes over 3 days on a voiding diary. | 4 weeks after completing all treatments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare fCO2 laser therapy vs. sham in relation to the change in the total number of voids per day as measured by the 3-day voiding diary. | Change in the total number of subject-reported stress urinary incontinence (SUI) episodes over 3 days based on voiding diaries. Each void and urine leak will be recorded over a 3 day period. Patients will determine if each leak is a stress leak or urge leak. Patients will be given a 3 day diary to complete. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported impression of SUI severity. | SUI severity as measured by the Patient Global Impression of Severity Scale (PGI-S). The subject will check the box that describes how their condition is now. Available options are 1= normal, 2 = mild, 3 = moderate, or 4 = severe. A higher score is equivalent to a worse outcome. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported impression of SUI improvement. | SUI improvement as measured by the Patient Global Impression of Improvement Scale (PGI-I). The subject will select one of the following options, (very much better, much better, a little better, no change, a little worse, much worse, very much worse) to describe their SUI symptoms now versus prior to study treatment. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported urogenital distress. | Change in urogenital distress as measured by the Urinary Distress Inventory questionnaire (UDI-6). The UDI-6 is a six point questionnaire, each question is scored as follows: 0 = no, 1 = not at all, 2 = somewhat, 3 = moderately, 4 = quite a bit. Scores are totaled and divided by 6, then multiplied by 25 to calculate the raw score. Higher scores = higher disability. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported impact of urinary incontinence on daily life as measured by the Incontinence Impact Questionnaire (IIQ-7). | Impact of urinary incontinence on daily life as measured by the Incontinence Impact Questionnaire (IIQ-7). The IIQ-7 assesses how a subject's problem effects activities, relationships, and feelings. It is a 7 point questionnaire. Each answer is scored as: 0=not at all, 1=slightly, 2=moderately, 3=greatly. The higher the score the more effected they are by their condition. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported impact of urinary incontinence on daily life as measured by the Incontinence Quality of Life Questionnaire (I-QOL) | The impact on urinary incontinence as measured by the Incontinence Quality of Life questionnaire (I-QOL). The I-QOL is a quality of life measure specific to persons with urinary incontinence. The survey consists of 22 incontinent-specific quality of life items, all having the following five-point ordinal response; 1=extremely, 2=quite a lot, 3=moderately, 4=a little, 5=not at all. The summed total score is transformed to a 0-100 scale ranging from 0 (poor quality of life) to 100 (maximum quality of life). | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported fecal incontinence. | Change in fecal incontinence as measured by the Cleveland clinic incontinence score (Wexner). Incontinence of stool may occur with or without urinary leakage. On the Cleveland clinic incontinence score the type of incontinence of stool (solid, liquid, gas, wears pad, lifestyle altered) are reported by the subject. Each question is measured as 0=never, 1=rarely, 2=sometimes, 4=usually, 5=always. The higher the score the more severe the condition. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported sexual function. | Change in sexual function as measured by the Female Sexual Function Index Questionnaire (FSFI). The FSFI is a 19 question survey. A lower score is equivalent to a higher degree of sexual function. Scores range from 0 to 95. | 8 weeks after the primary endpoint | 
| To compare fCO2 laser therapy vs. sham in relation to the change in subject-reported pain and discomfort. | Change in pain and discomfort as measured by the Visual Analog Scale (VAS). The VAS is a validated questionnaire that assesses pain on a scale from 0=no pain to 10=Worst possible pain. A higher score is equivalent to a worse outcome. | 8 weeks after the primary endpoint | 
| Durability to determine whether subjects in the fCO2 laser therapy group continue to have a higher responder rate than the sham group. | A patient is called a responder if there is a greater than or equal to 50% reduction from baseline in the number of subject-reported SUI episodes over 3 days on a voiding diary. Change in the total number of subject-reported stress urinary incontinence (SUI) episodes over 3 days based on voiding diaries. Each void and urine leak will be recorded over a 3 day period. Patients will determine if each leak is a stress leak or urge leak. Patients will be given a 3 day diary to complete. | 8 weeks after the primary endpoint. | 
| Determine the safety of fCO2 laser therapy compared to sham. | Safety of the fCO2 laser therapy compared to sham will be assessed in relation to the incidence of adverse events. | 8 weeks after the primary endpoint. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Laser Therapy