Evaluating the Efficacy of Temperature-controlled Radiofrequency (TRF) in the Treatment of Vulvovaginal Atrophy.

Randomized Multicenter Clinical Trial for Evaluating the Efficacy of Temperature-controlled Radiofrequency Compared With Topical Estriol in the Treatment of Vulvovaginal Atrophy in Postmenopausal Women

This project will be a prospective, multicenter, randomized cohort study. The investigators will select patients with vulvovaginal atrophy who have indications for treatment, and set up the experimental group (Peninsula temperature-controlled radiofrequency therapeutic apparatus group) and the control group (promestriene vaginal soft capsules group). Changes in vaginal exfoliated cell maturity index (MV), score of vaginal symptoms and signs, vaginal health index score (VHIS), female sexual function index score (FSFI), visual analogue score (VAS) before and after treatment, and adverse effects will be observed to analyze the safety and efficacy of temperature-controlled radiofrequency therapy for vulvovaginal atrophy in postmenopausal women.

Study Overview

• Status: Recruiting
• Conditions: Postmenopausal Vulvovaginal Atrophy
• Intervention / Treatment: Device: high frequency fulguration equipment; Drug: promestriene vaginal soft capsules

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lijun Zhao, Dr.; Phone Number: 0086-10-88324384; Email: lilyzhaopku@163.com

Study Locations

• China
  • Beijing
    • Peking, Beijing, China, 100044
      • Recruiting
      • Peking University People's University
      • Contact: Lijun Zhao, Dr.; Email: lilyzhaopku@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Menopausal time at least one year.
• Genitourinary Syndrome of Menopause (GSM) related symptoms with moderate or severe intensity, such as dryness and dyspareunia, etc.
• Blood FSH≥30 IU/L (30mIU/mL)。
• Clinical symptoms and signs of vaginal atrophy score≥15.
• Breast ultrasound examination was grade 1-3 within 9 months before the study.
• Voluntary participation in clinical trials and signed informed consent.
• Patients followed the treatment regimen and completed the study.

Exclusion Criteria (one of the following criteria is excluded) :

• The patients who did not meet the inclusion criteria
• Received Estrogen replacement therapy (including local and systemic medication) within 3 months.
• Received any medicine (such as Baofukang suppository) to treat vulvovaginal atrophy within 3 months.
• Corticosteroids were used within 6 weeks. Long-term corticosteroids were used (intermittent nasal or skin application, eye drops and ears are allowed).
• Other experimental drugs were used within 1 month.
• Received vaginal laser therapy within 6 months.
• Patients with acute urinary tract infection;
• Patients with acute genital tract infection (genital herpes, trichomonad, fungal vaginitis; gonococcus, mycoplasma, chlamydia infection and bacterial vaginosis, etc.);
• Patients with pelvic organ prolapse greater than or equal to stage II;
• Patients with metal intrauterine device (IUD)；
• Patients with precancerous lesions or malignant tumors of vagina and cervix;
• Patients with serious heart, liver, brain, kidney, endocrine diseases, etc.
• Allergic to control drug and excipients.
• Other malignancies are known or suspected.
• With estrogen-dependent neoplasm.
• Confirm a history of depression or serious mental illness.
• There were consciousness barriers and communication barriers that could not cooperate with the experiment.
• Patients considered unsuitable for this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRF group; the group who treated with temperature controlled radiofrequency	Device: high frequency fulguration equipment; All subjects will be carried out with 3 standard protocol TRF treatments to the vulvovaginal tissue using the high frequency fulguration equipment (Shenzhen Peninsula Medical co., Ltd) at 10-day to 15-day intervals. Radiofrequency energy was applied to the vaginal canal through a specialized probe combining monopolar and bipolar treatment modes. Monopolar treatment mode is for 15 minutes. Aim the three indication points A, B and C on the probe to the direction of 12 o'clock in turn. Each area should be treated for about 5 minutes. Rotate the probe clockwise when changing the area for treatment.Bipolar treatment mode is for 10 minutes. Firstly, indication point A is aimed to 12 o'clock for 5-minutes treatment and then the probe is rotated 90°clockwise for another 5-minutes treatment. The power setting will be 35-40w, and the target temperature setting will be 40 to 45℃, titrated to subject tolerance.; Other Names: temperature controlled radiofrequency
Active Comparator: Estriol group; the group who treated with promestriene vaginal soft capsules	Drug: promestriene vaginal soft capsules; Promestriene vaginal soft capsules（Zhejiang Anbao Pharmaceutical Co. LTD）will be used 10mg once a day for continuous 20 days.; Other Names: Estriol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change value of vaginal maturation index (VMI) compared with baseline	The Vaginal Maturation Index (VMI) is an assessment done to establish the oestrogen effect in the body. The vaginal cytology specimens were collected from the mid-vaginal-wall before treatment and fixed in ThinPrep solution. The VMI is a ratio obtained with three main cell types found in the vaginal walls: parabasal cells(P), Intermediate cells (I) and superficial cells(S). The findings will be presented in a 0/0/0 format. VMI = [1 × (% superficial cells)] + [0.6 × (% intermediate cells)] + [0.2 × (% parabasal cells)]. This index enabled us to objectively evaluate the differential count of each cell group expressed as a percentage. The greater the degree of vaginal atrophy, the greater the estrogen deficiency. When at most 30% of the deep cells were present in the vaginal smears, mild hypoestrogenism was diagnosed. A deep cell percentage between 30% and 49% indicated moderate hypoestrogenism and a more than 50% deep cell percentage indicated hypoestrogenism.	The two groups will be visited on day 0, 1 month and 3 months after the last treatment.
the changes of vaginal symptoms and signs scores compared with baseline	Symptoms (vaginal dryness, pruritus, burning, pain, shallow dyspareunia, deep dyspareunia) will be individually scored by women and signs (vaginal mucosa and petechia, vaginal elasticity, mucosal luster) will be individually scored by the investigators as 0 = absence, 1 = mild, 2 = moderate, and 3 = severe alteration. In addition, a composite score of symptoms and signs will calculated by the addition of the intensity scores of all individual symptoms and signs (range, 0-27: The higher the score is, the more severe the genitourinary atrophy is.). Symptoms and signs score (SSC) will be obtained at each visiting to assess the effect of treatment on all individual.	The two groups will be visited on day 0, day 20（the control group is day 21），1 month and 3 months after the last treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes of vaginal health index score (VHI) compared with baseline	VHI scores accounted for the following five parameters: elasticity, fluid volume, pH, epithelial integrity, and moisture. Each parameter will be graded from 1 (worst condition) to 5 (best condition) with a maximum possible score of 25 points. Scores less than 15 are indicative of vaginal atrophy.	The two groups will be visited on day 0, day 20（the control group is day 21），1 month and 3 months after the last treatment.
The changes of female sexual function index score (FSFI) compared with baseline	Sexual function will be measured using the Female Sexual Function Index (FSFI). This questionnaire, which contains 19 items, was developed as a brief, but multidimensional, self-reporting instrument to assess the key dimensions of female sexual function. It was developed based on a group of normal female controls and age-matched women who met the DSM-IV-TR criteria for female sexual arousal disorder (FSAD). The FSFI addresses six domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) and provides full-scale scores ranging from 2.0 (severe dysfunction) to 36.0 (absence of dysfunction). The validated FSFI version for the Chinese language will be used. A cutoff score of 26.55 will be used to differentiate the presence or absence of sexual dysfunction.	The two groups will be visited on day 0, 1 month and 3 months after the last treatment.
The changes of visual analogue score (VAS) compared with baseline	The Visual Analogue Scale (VAS) is a popular tool for the measurement of pain. The pain is represented by 11 Numbers from 0 to 10, 0 is painless and 10 is the most painful. The patient chooses one of these 11 Numbers to represent the pain level according to her own pain level.	The two groups will be visited on day 0, day 20（the control group is day 21），1 month and 3 months after the last treatment.

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Chinese Association of Plastics and Aesthetics

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: vulvovaginal atrophy; Genitourinary Syndrome of Menopause; temperature-controlled radiofrequency; postmenopausal woman
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy
• Other Study ID Numbers: Version 2.0；20200221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No