Back to resultsUse of Fractional CO2 Laser for the Treatment of Vulvovaginal Atrophy: a Double-blinded Randomized Placebo-controlled Clinical Trial. (CO2VVA)
Primary Purpose
Vulvovaginal Atrophy
Status
Completed
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Vaginal laser application
Sponsored by
About this trial
This is an interventional treatment trial for Vulvovaginal Atrophy
Eligibility Criteria
Inclusion Criteria:
Healthy women with menopausal status (>1 year amenorrhea) AND with moderate to severe symptoms of VVA as measured by the MBS score ≥2.
Exclusion Criteria:
- Acute or recurrent urogenital infections
- Prolapse ≥ grade 3 according to the Pelvic Organ Prolapse Quantification System
- Hormonal replacement therapy within the last 6 months before study entry
- Use of local estrogens, moisturizers, lubricants or homeopathic preparations within the last 3 months
- Pelvic floor physiotherapy for pelvic floor disorders within the last 3 months
- Any condition that could interfere with study compliance
Sites / Locations
- UZ Leuven
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Laser
Sham
Arm Description
In this arm, participants will have 3 real laser treatments first, followed by 3 consecutive sham treatments.
In this arm, participants will have 3 sham treatments first, followed by 3 consecutive real laser treatments.
Outcomes
Primary Outcome Measures
Primary outcome measure is the change in severity of most bothersome symptom (MBS)
The MBS is derived from a selected list of symptoms (consisting of the four most common symptoms of vaginal dryness, vaginal itching/irritation, vaginal soreness and dyspareunia). At baseline, participants are instructed to rate each of these symptoms as not present, mild, moderate or severe and then are asked to select a single symptom among those classified as moderate or severe as the MBS. The MBS is then followed through to the end of treatment, and the change in its severity is used to evaluate symptomatic improvement.
Secondary Outcome Measures
Assessment of the effect of treatment on the female urogenital health, by means of the globally validated "Vaginal Health Index Score" (VHIS).
The VHIS includes scoring of vaginal moisture, vaginal fluid volume, vaginal elasticity, vaginal pH, and vaginal epithelial integrity on a scale of 1 (poorest) to 5 (best) according to the methods of Robert Wood Johnson Medical School. The lower the score, the greater the atrophy.
Assessment of the effect of treatment on the female urogenital health, by means of vaginal pH measurements.
Measurement of the vaginal pH is considered useful, effective, and inexpensive19. Studies have shown that a vaginal pH greater than 5.0 is associated with decreased serum estradiol and menopause. The vaginal pH will be measured with the use of a pH indicator strip and should be sampled from the lateral vaginal wall. This technique is validated. Such strips are available in every clinic.
Assessment of the effect of treatment on VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia and dysuria) using the Visual Analog Scale (0-10cm, continuous scale).
For this measurement a continuous Visual Analogue Scale (0-10cm) is used (0 is no pain, 10 is the maximum pain score).
Assessment of the rate of patient satisfaction by means of the Patient Global Impression of Improvement (PGI), using a 5-point Likert scale (1=much worse, 2=worse, 3=same, 4=better, 5=much better).
Assessment of the degree of discomfort of the treatment procedure by the patient, by mean of a VAS-score(0-10cm, continuous scale).
For this measurement a continuous Visual Analogue Scale (0-10cm) is used (0 is no pain, 10 is the maximum pain score).
Assessment of the degree of difficulty encountered by the physician in performing the treatment, by means of a 5-point Likert scale (1=very difficult, 2=difficult, 3=neutral, 4=easy, 5=very easy).
Assessment of the long term satisfaction with, and the longevity of the effect of laser therapy, measured by the need for, and the timing for repeating the same, or initiating an alternative therapy.
Assessment of the vaginal wall thickness using in vivo microscopy (vaginal focal depth measurement).
VVA is associated with thinning of the vaginal epithelial layer due to the declining levels of circulating estrogen associated with VVA. Therefore, measurement of the vaginal wall thickness offers an objective measure in the diagnosis and evaluation of VVA and its treatment24. Vaginal focal depth measurements will be performed using the Cytocam-Incident Dark Field device (IDF), a validated technique to quantitatively assess vaginal microcirculation25. As part of the pelvic examination, the handheld device, covered with a sterile disposable cap, will gently be placed into contact with the anterior vaginal wall, 3cm above the hymen, assessing the distance between the subepithelial microcirculation and the epithelial surface in micrometers.
At all clinical visits baseline/study parameters will be assessed before treatment and procedure related outcomes will be assessed after the procedure.
Effect of treatment, in sexually active patients, on female sexual function, by means of the validated "Female Sexual Function Index" (FSFI) specific questionnaire
The FSFI is a brief, 19-item self-report measure of female sexual function that provides scores on six domains of sexual function as well as a total score. The six domains include: desire (2 items; score range 1-5; factor 0.6; minimum score 1.2; maximum score 6.0), arousal (4 items; score range 0-5; factor 0.3; minimum score 0; maximum score 6.0), lubrication (4 items; score range 0-5; factor 0.3; minimum score 0; maximum score 6.0), orgasm (3 items; score range 0-5; factor 0.4; minimum score 0; maximum score 6.0), satisfaction (3 items; score range 0-5; factor 0.4; minimum score 0; maximum score 6.0), and pain (3 items; score range 0-5; factor 0.4; minimum score 0; maximum score 6.0).
Full Scale Score Range: minimum score 2.0, maximum score 36.0. Higher values represent a better outcome.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04021966
Brief Title
Use of Fractional CO2 Laser for the Treatment of Vulvovaginal Atrophy: a Double-blinded Randomized Placebo-controlled Clinical Trial.
Acronym
CO2VVA
Official Title
Use of Fractional CO2 Laser for the Treatment of Vulvovaginal Atrophy: a Double-blinded Randomized Placebo-controlled Clinical Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
September 27, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
prof. dr. Jan Deprest
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Purpose of the trial is to study the efficacy of fractional laser in alleviating genitourinary symptoms in menopausal women.
Primary outcome of the study is the efficacy of the laser procedure, intended as the amelioration of the severity of most bothersome symptom (MBS).
Therefore we conducted a single center, double-blinded randomized placebo-controlled cross-over trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vulvovaginal Atrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Laser
Arm Type
Experimental
Arm Description
In this arm, participants will have 3 real laser treatments first, followed by 3 consecutive sham treatments.
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
In this arm, participants will have 3 sham treatments first, followed by 3 consecutive real laser treatments.
Intervention Type
Procedure
Intervention Name(s)
Vaginal laser application
Intervention Description
One laser treatment cycle consists of 3 vaginal laser applications with a 4-weeks interval. Each application lasts around 5 minutes.
The vaginal laser procedure will be performed in an outpatient setting, not requiring any specific preparation, analgesia or anesthesia, by one of two experienced operators.
A vaginal probe will be gently inserted and manually rotated to provide a 360° treatment of the vaginal mucosa.
Primary Outcome Measure Information:
Title
Primary outcome measure is the change in severity of most bothersome symptom (MBS)
Description
The MBS is derived from a selected list of symptoms (consisting of the four most common symptoms of vaginal dryness, vaginal itching/irritation, vaginal soreness and dyspareunia). At baseline, participants are instructed to rate each of these symptoms as not present, mild, moderate or severe and then are asked to select a single symptom among those classified as moderate or severe as the MBS. The MBS is then followed through to the end of treatment, and the change in its severity is used to evaluate symptomatic improvement.
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Secondary Outcome Measure Information:
Title
Assessment of the effect of treatment on the female urogenital health, by means of the globally validated "Vaginal Health Index Score" (VHIS).
Description
The VHIS includes scoring of vaginal moisture, vaginal fluid volume, vaginal elasticity, vaginal pH, and vaginal epithelial integrity on a scale of 1 (poorest) to 5 (best) according to the methods of Robert Wood Johnson Medical School. The lower the score, the greater the atrophy.
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the effect of treatment on the female urogenital health, by means of vaginal pH measurements.
Description
Measurement of the vaginal pH is considered useful, effective, and inexpensive19. Studies have shown that a vaginal pH greater than 5.0 is associated with decreased serum estradiol and menopause. The vaginal pH will be measured with the use of a pH indicator strip and should be sampled from the lateral vaginal wall. This technique is validated. Such strips are available in every clinic.
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the effect of treatment on VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia and dysuria) using the Visual Analog Scale (0-10cm, continuous scale).
Description
For this measurement a continuous Visual Analogue Scale (0-10cm) is used (0 is no pain, 10 is the maximum pain score).
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the rate of patient satisfaction by means of the Patient Global Impression of Improvement (PGI), using a 5-point Likert scale (1=much worse, 2=worse, 3=same, 4=better, 5=much better).
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the degree of discomfort of the treatment procedure by the patient, by mean of a VAS-score(0-10cm, continuous scale).
Description
For this measurement a continuous Visual Analogue Scale (0-10cm) is used (0 is no pain, 10 is the maximum pain score).
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the degree of difficulty encountered by the physician in performing the treatment, by means of a 5-point Likert scale (1=very difficult, 2=difficult, 3=neutral, 4=easy, 5=very easy).
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the long term satisfaction with, and the longevity of the effect of laser therapy, measured by the need for, and the timing for repeating the same, or initiating an alternative therapy.
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Assessment of the vaginal wall thickness using in vivo microscopy (vaginal focal depth measurement).
Description
VVA is associated with thinning of the vaginal epithelial layer due to the declining levels of circulating estrogen associated with VVA. Therefore, measurement of the vaginal wall thickness offers an objective measure in the diagnosis and evaluation of VVA and its treatment24. Vaginal focal depth measurements will be performed using the Cytocam-Incident Dark Field device (IDF), a validated technique to quantitatively assess vaginal microcirculation25. As part of the pelvic examination, the handheld device, covered with a sterile disposable cap, will gently be placed into contact with the anterior vaginal wall, 3cm above the hymen, assessing the distance between the subepithelial microcirculation and the epithelial surface in micrometers.
At all clinical visits baseline/study parameters will be assessed before treatment and procedure related outcomes will be assessed after the procedure.
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
Title
Effect of treatment, in sexually active patients, on female sexual function, by means of the validated "Female Sexual Function Index" (FSFI) specific questionnaire
Description
The FSFI is a brief, 19-item self-report measure of female sexual function that provides scores on six domains of sexual function as well as a total score. The six domains include: desire (2 items; score range 1-5; factor 0.6; minimum score 1.2; maximum score 6.0), arousal (4 items; score range 0-5; factor 0.3; minimum score 0; maximum score 6.0), lubrication (4 items; score range 0-5; factor 0.3; minimum score 0; maximum score 6.0), orgasm (3 items; score range 0-5; factor 0.4; minimum score 0; maximum score 6.0), satisfaction (3 items; score range 0-5; factor 0.4; minimum score 0; maximum score 6.0), and pain (3 items; score range 0-5; factor 0.4; minimum score 0; maximum score 6.0).
Full Scale Score Range: minimum score 2.0, maximum score 36.0. Higher values represent a better outcome.
Time Frame
Will be measured at baseline and during every next visit (vaginal applications and follow-up visits); ie. 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 3 months, 6 months and 12 months post treatment
10. Eligibility
Sex
Female
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy women with menopausal status (>1 year amenorrhea) AND with moderate to severe symptoms of VVA as measured by the MBS score ≥2.
Exclusion Criteria:
Acute or recurrent urogenital infections
Prolapse ≥ grade 3 according to the Pelvic Organ Prolapse Quantification System
Hormonal replacement therapy within the last 6 months before study entry
Use of local estrogens, moisturizers, lubricants or homeopathic preparations within the last 3 months
Pelvic floor physiotherapy for pelvic floor disorders within the last 3 months
Any condition that could interfere with study compliance
Facility Information:
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Use of Fractional CO2 Laser for the Treatment of Vulvovaginal Atrophy: a Double-blinded Randomized Placebo-controlled Clinical Trial.
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