Radiofrequency and Hybrid Fractional Laser for Vaginal Rejuvenation

• ClinicalTrials.gov Identifier: NCT03316950
• Recruitment Status: Active, not recruiting
• First Posted: October 23, 2017
• Last Update Posted: February 5, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: American Society for Aesthetic Plastic Surgery
• Information provided by (Responsible Party): Jeffrey M. Kenkel, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Vaginal Atrophy	Device: IntraGen RF; Device: DiVA	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled Trial Evaluating Radiofrequency and Hybrid Fractional Laser for Vaginal Rejuvenation
• Actual Study Start Date: June 15, 2018
• Estimated Primary Completion Date: May 30, 2021
• Estimated Study Completion Date: August 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: IntraGen RF; 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; 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.
Sham Comparator: IntraGen Sham; Patients will undergo all acts of receiving radiofrequency treatment, but no direct energy will be applied. Patients will have 3 sham treatments space one month apart. Each treatment session will be a total of 20 minutes. Prior to sham 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; 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.
Experimental: DiVA; 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; 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.
Sham Comparator: DiVA Sham; Patients randomized into the DiVA sham group will undergo all acts of receiving DiVA treatment, but not direct energy will be applied. Patients will have a total of 3 treatments, spaced 1 month apart. Each treatment will last approximately 10 minutes. Prior to sham 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; 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.
Experimental: Dual Treatment; 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; 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.; Device: 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.

Outcome Measures

Primary Outcome Measures :

1. Vulvovaginal Symptoms Questionnaire [ Time Frame: 12 months - 18 months ]
   questionnaire assessing vulvovaginal symptoms in postmenopausal women including discomfort, emotions, life-impact, and sexual impact
2. Vaginal Laxity Questionnaire [ Time Frame: 12 months - 18 months ]
   validated questionnaire assessing laxity

Secondary Outcome Measures :

1. Zimmern Probe [ Time Frame: 12 months - 18 month ]
   measures vaginal wall elasticity
2. Urogenital Distress Short Form (UDI-6) [ Time Frame: 12 months - 18 months ]
   questionnaire assessing urinary incontinence
3. Incontinence Impact Questionnaire Short Form (IIQ-7) [ Time Frame: 12 months - 18 months ]
   questionnaire assessing urinary incontinence
4. Female Sexual Function Index (FSFI) [ Time Frame: 12 months - 18 months ]
   questionnaire assessing sexual dysfunction
5. Histological changes [ Time Frame: 12 months - 18 months ]
   Biopsies taken of the anterior vaginal wall will be analyzed for histology and gene expression

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

American Society for Aesthetic Plastic Surgery

Investigators

• Principal Investigator: Jeffrey Kenkel, MD; Chair & Professor

More Information

Publications:

Alinsod RM. Transcutaneous temperature controlled radiofrequency for orgasmic dysfunction. Lasers Surg Med. 2016 Sep;48(7):641-5. doi: 10.1002/lsm.22537. Epub 2016 May 19. Erratum in: Lasers Surg Med. 2017 Sep;49(7):727.

Millheiser LS, Pauls RN, Herbst SJ, Chen BH. Radiofrequency treatment of vaginal laxity after vaginal delivery: nonsurgical vaginal tightening. J Sex Med. 2010 Sep;7(9):3088-95. doi: 10.1111/j.1743-6109.2010.01910.x.

Sekiguchi Y, Utsugisawa Y, Azekosi Y, Kinjo M, Song M, Kubota Y, Kingsberg SA, Krychman ML. Laxity of the vaginal introitus after childbirth: nonsurgical outpatient procedure for vaginal tissue restoration and improved sexual satisfaction using low-energy radiofrequency thermal therapy. J Womens Health (Larchmt). 2013 Sep;22(9):775-81. doi: 10.1089/jwh.2012.4123. Epub 2013 Aug 16.

Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligaro A. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015 Jan;30(1):429-36. doi: 10.1007/s10103-014-1677-2. Epub 2014 Nov 20.

Paul M, Blugerman G, Kreindel M, Mulholland RS. Three-dimensional radiofrequency tissue tightening: a proposed mechanism and applications for body contouring. Aesthetic Plast Surg. 2011 Feb;35(1):87-95. doi: 10.1007/s00266-010-9564-0. Epub 2010 Sep 11.

Peet J. Evaluation of the Safety and Efficacy of Hybrid Fractional 2940 nm and 1470 nm Lasers for Treatment of Vaginal Tissue: Pilot Study. [White paper].

• Responsible Party: Jeffrey M. Kenkel, Chair, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03316950
• Other Study ID Numbers: STU 012017-006
• First Posted: October 23, 2017
• Last Update Posted: February 5, 2020
• Last Verified: February 2020

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
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Jeffrey M. Kenkel, University of Texas Southwestern Medical Center:

postmenopause; rejuvenation; radiofrequency; diva

Additional relevant MeSH terms:

Atrophy; Pathological Conditions, Anatomical