Radiofrequency and Hybrid Fractional Laser for Vaginal Rejuvenation

Study Overview
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Brief Summary
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This is a single-center, randomized, prospective study designed to evaluate the efficacy of radiofrequency and hybrid fractional laser for vaginal rejuvenation. 120 subjects will be screened with 100 undergoing a three-part treatment of the vulvovaginal area IntraGen RF unit, IntraGen RF unit placebo, DiVa HFL unit, or DiVa HFL unit placebo. These treatments will be spaced one month apart and last about 25 minutes each. Each subject will be screened, undergo testing at baseline, and will be followed conservatively with no further therapy until they reach 6 months after the initiation of the designated treatment. At that time, all subjects will undergo subjective and objective testing. Those in the treatment group will be followed to 9 and 12 months after the initiation of treatment with appropriate analysis. Those in the placebo group will be provided a three-part treatment of the vulvovaginal area with the IntraGen RF unit and DiVA HFL unit. These treatments will be spaced one month apart and last about 25 minutes each. Six months after receiving three treatments of the dual therapy these patients will undergo subjective and objective testing. The primary outcome measure is improvement in vulvovaginal symptoms measured by the validated Vulvovaginal Symptoms Questionnaire. Data obtained from each investigation will be recorded in a password-protected digital spreadsheet, REDCap database and descriptive statistics will be obtained.

Detailed Description
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Vaginal rejuvenation is a catch-all term of trendy procedures which claim to provide relief of many issues affecting women's health, ranging from postmenopausal vulvovaginal symptoms (i.e. dryness, burning, itching), stress urinary incontinence, sexual dysfunction or discomfort, vaginal laxity, and labial appearance, amongst others2,3. Several companies have emerged with non-invasive or minimally-invasive technologies to alleviate these conditions which operate by radiofrequency delivery (IntraGen by Jeisys), Hybrid Fractional Laser (diVa by Sciton), or fractional CO2 laser (Mona Lisa Touch by Cynosure and Femi Lift by Alma Laser)4. All of these technologies work theoretically by remodeling extracellular matrix configuration. It is of important note that radiofrequency therapies are typically delivered at 45-55 degrees Celsius in the tissues whereas the laser based products heat up to 60-70 degrees Celsius5. It is believed that neocollagenesis may only start if the temperatures are high enough and that such changes in the collagen matrix of the vagina could lead to durable vaginal wall changes. Sciton's diVa is hybrid fractional laser with wavelengths of 2940 nm and 1470 nm for ablation and coagulation, respectively, to treat vaginal tissue6. It is not known whether the changes experienced by patients are due to the reconfiguration of the extracellular matrix (ECM) deep in the vaginal wall or related to the acute swelling and inflammatory processes that occur at the surface of the vagina after these rejuvenation procedures. The early anecdotal success reported on some user websites might be attributable to surface changes that may not be lasting or to possibly more lasting deeper muscular vaginal wall changes, which may or may not be beneficial. Based on the answer to this first set of questions, we might possibly surmise how such changes will ultimately improve vaginal dryness and/or stress urinary incontinence complaints. An overriding question and concern is: Assuming these treatments induce collagen changes in the vagina, is it safe to induce such changes? If changes occur, are they long lasting? Can it age the vagina instead of making it younger? What are the long-term effects of doing so? Is tissue tightening really scar formation that may be deleterious in the future? The histological, genetic and dynamic changes following vaginal rejuvenation have never been studied.

Official Title
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A Randomized, Placebo-Controlled Trial Evaluating Radiofrequency and Hybrid Fractional Laser for Vaginal Rejuvenation

Conditions
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Vaginal Atrophy

Intervention / Treatment
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* Device: IntraGen RF
* Device: DiVA
* Device: Placebo (DIVA/IntraGen combined)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women should be between 40 and 65 years of age Women should be post-menopausal Women should be amenorrheic for at least 12 months Postmenopausal women presenting with one or more of the following: Vulvar itching Vulvar burning or stinging Vulvar pain Vulvar irritation Vulvar dryness Discharge from subject's vulva or vagina Odor from subject's vulva or vagina Exclusion Criteria: Unable to commit to future appointments within one year Planning on moving away from Dallas within one year History of other energy-based vaginal therapy within one year Vaginal hormone replacement therapy must have a one month washout period prior to treatment and discontinued use for duration of study, systemic replacement is not excluded Prior labiaplasty, or vaginal injections of fat or fillers within 6 months Prior anti-incontinence surgery in the last 12 months Urinary incontinence requiring more than 2 pads/day Clinically significant pelvic organ prolapse (POP) Urinary tract infection in the past 3 months Unstable diabetes Ongoing chemotherapy Immunodeficiency status (steroid intake, ongoing chemotherapy) Diffuse pain syndrome or chronic pain requiring daily narcotics Chronic vaginitis including bacterial vaginosis, HPV, herpes, or other active STI Recent abnormal Papanicolaou test result Recent abnormal pelvic exam (i.e. concerning lesions) Vulvar dermatologic pathology requiring local steroid use Undiagnosed abnormal genital bleeding If less than two years postmenopausal, not using a medically approved method of contraception (i.e. oral, transdermal, implanted contraceptives, intrauterine device, diaphragm, condom, etc.) Pregnancy History of genital fistula or a thin rectovaginal septum Uncontrolled psychiatric conditions (well-controlled depression/anxiety is not excluded) Body Mass Index > 35 Actively participating in or planning on participating in pelvic floor muscle strengthening exercise Presence of pacemaker, AICD, or other electrical health maintenance device

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IntraGen RF<br>Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. | Device: IntraGen RF<br>* IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.<br>|
| Experimental: DiVA<br>Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. | Device: DiVA<br>* DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.<br>|
| Sham Comparator: Placebo Arm<br>Patients randomized into the Placebo arm will include participants from the DiVa PlaceboGroup and IntraGen Placebo Group combined and will receive treatment based on the DiVA Sham and IntraGen Sham protocols. DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue. | Device: Placebo (DIVA/IntraGen combined)<br>* (DIVA/IntraGen combined) IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.<br>|
| Experimental: Dual Treatment<br>Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. | Device: IntraGen RF<br>* IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.<br>Device: DiVA<br>* DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vulvovaginal Symptoms Questionnaire | VSQ is a 21-item validated survey designed to assess postmenopausal quality-of-life parameters, namely vulvovaginal symptoms, emotions, life and sexual impact. Min: 0; Max: 21 Higher score would indicate greater number of symptoms. | Baseline, 3 Month Post- treatments and 6 Month Post Treatments | 
| Vaginal Laxity Questionnaire | The VLQ is a Likert scale with seven responses regarding self-reported vaginal laxity; answer option range from Very Loose to Very Tight. Min: 1; Max: 7 A higher score would indicate Very Tight response provided by the subject. | Baseline, 3 Months Post Treatments and 6 Months Post Treatments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceived Changes in Vaginal Laxity as Measured by Zimmern Probe at 3 Months Post Treatment | Perceived changes in vaginal laxity is measured by Zimmern probe which measures vaginal wall elasticity. | Baseline and 3 Months Post Treatment | 
| Perceived Changes in Vaginal Laxity as Measured by Zimmern Probe at 6 Months Post Treatment | Perceived changes in vaginal laxity is measured by Zimmern probe which measures vaginal wall elasticity. | Baseline and 6 Months Post Treatment | 
| Urogenital Distress Short Form (UDI-6) | UDI-6 measures multiple domains to assess for presence and severity of physical symptoms such as frequency in urination, urine leakage and pain/discomfort. Min: 0; Max: 100 Higher score would indicate a higher disability | Baseline, 3 Months Post Treatments and 6 Months Post Treatments | 
| Incontinence Impact Questionnaire Short Form (IIQ-7) | The Incontinence Impact Questionnaire assesses the impact and extent of incontinence on patients' everyday lives. Min: 0; Max: 100 Higher scores corresponds to greater degree of disability. | Baseline, 3 Months Post Treatments and 6 Months Post Treatments | 
| Female Sexual Function Index (FSFI) | The FSFI is a 19-item validated questionnaire that assesses several domains of sexual function including, desire, arousal, lubrication, orgasm, satisfaction and pain. Min: 2; Max: 36 Higher scores indicate fewer symptoms and greater sexual satisfaction. | Baseline, 3 Months Post Treatments and 6 Months Post Treatments | 
| Gene Expression- Col1A1 as Measured by Fold Change | Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline | Baseline and 3 Months Post Treatments | 
| Gene Expression- Col3A1 as Measured by Fold Change | Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline | Baseline and 3 Months Post Treatments | 
| Gene Expression- ELN as Measured by Fold Change | Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline | Baseline and 3 Months Post Treatments | 
| Gene Expression- LOX as Measured by Fold Change | Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline | Baseline and 3 Months Post Treatments | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postmenopause, rejuvenation, radiofrequency, diva