Vulva; AtrophyNCT07246616
Efficacy and Safety of CO₂ Laser Therapy Combined With Collagen Cream in Managing Vulvo-Vaginal Atrophy: A Randomized, Controlled Study on Symptom Relief and Microbiome Modulation
A study testing SmartXide2 treatment plus the application of Palingen cream in people with Vulva; Atrophy, run by Institute for Social Security, Republic of San Marino at 1 site in San Marino.
Trial summary
This study evaluated a new treatment for postmenopausal women suffering from vulvo-vaginal atrophy (VVA), a condition that causes dryness, burning, and pain. Researchers tested whether combining CO₂ laser therapy with a collagen-based cream could improve symptoms more effectively than laser treatment alone. Read more about this study
- Who is it for?
- Ages 35 to 75 years, women only
- Conditions the study is for
- Vulva; Atrophy
- What is being tested?
- SmartXide2 treatment plus the application of Palingen cream
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSan Marino
- Study dates
- 1 Jun 2024to 31 Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women with absence of menstrual cycle for at least 12 months, diagnosed with vulvovaginal atrophy (VVA) and presenting with related symptoms such as dryness, introital and deep dyspareunia, bleeding during intercourse, itching, or burning related to the severity of VVA, whether spontaneous or drug-induced (radio- or chemotherapy), either with a single symptom or a combination thereof.
- Age between 35 and 75 years;
- Patients unresponsive or dissatisfied with previous topical estrogen therapy, or presenting contraindications to the use of local and/or systemic estrogens.
- Previous negative Pap test performed within 3 years prior to study enrollment.
Who cannot join
- • Pregnancy or breastfeeding;
- Presence of preneoplastic or neoplastic lesions of the cervix, vagina, or vulva;
- Presence of active genital and/or urinary tract infection;
- Relative or absolute dermatological contraindications to laser use;
- Ongoing hormonal therapy (systemic or local);
- Neurological and/or psychiatric disorders;
- Chronic systemic autoimmune or metabolic diseases;
- Refusal to provide informed consent.
Trial locations and contacts
1 site in 1 country.
San Marino1 site
UOC di Ostetricia e Ginecologia, Ospedale di Stato della Repubblica di San Marino, Istituto per la Sicurezza Sociale (ISS)
San Marino, Borgo Maggiore, 47893
About this study
This study evaluated a new treatment for postmenopausal women suffering from vulvo-vaginal atrophy (VVA), a condition that causes dryness, burning, and pain. Researchers tested whether combining CO₂ laser therapy with a collagen-based cream could improve symptoms more effectively than laser treatment alone.
Read the detailed description
Sixty women participated in the study. Results showed that the combination treatment provided greater relief from discomfort and helped restore vaginal health, with fewer side effects. This approach may offer a safe and effective alternative for women who cannot use hormone-based therapies.
- Conditions
- Vulva; Atrophy
- Being tested
- SmartXide2 treatment plus the application of Palingen cream, Laser Therapy Only (Control Group)
- Keywords
- Vulva, Atrophy, Co2, Vulvo-vaginal, Microbiome, Modulation, Laser, Theraphy, Collagen, Collagen Cream
- Medical subject headings
- Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SmartXide2 treatment plus the application of Palingen creamDevice
Patients will be randomized into two groups: one called the "control" group, in which patients will receive only the SmartXide2 treatment, and the second called "PALINGEN," in which patients will receive SmartXide2 treatment plus the application of Palingen cream.
Laser Therapy Only (Control Group)Device
Participants receive fractional CO₂ laser therapy according to the standard protocol for vulvo-vaginal atrophy.
No additional topical treatment is applied.
Laser sessions are performed at baseline (Day 0), Day 30, and Day 60.
Follow-up visits include clinical evaluation and microbiome sampling at each time point.
| Study group | Role | What they receive |
|---|---|---|
| Laser Therapy Only (Control Group) | Active comparator | Participants receive fractional CO₂ laser therapy according to the standard protocol for vulvo-vaginal atrophy.
No additional topical treatment is applied.
Laser sessions are performed at baseline (Day 0), Day 30, and Day 60.
Follow-up visits include clinical evaluation and microbiome sampling at each time point. Receives: Device: SmartXide2 treatment plus the application of Palingen cream; Device: Laser Therapy Only (Control Group) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in VVA (Vulvo-Vaginal Atrophy) symptoms
Assessed after 30 and 60 days of treatment using the Visual Analogue Scale (VAS).
The VAS was used to quantify symptom intensity such as burning, dryness, itching, dyspareunia, and pain.
Improvement was measured as the difference in VAS scores before and after treatment.
Measured: Outcome: Improvement in symptoms associated with vulvo-vaginal atrophy (VVA) Assessment Tool: Visual Analogue Scale (VAS) Time Frame: Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second
Secondary outcomes (3)
Vaginal Microbiome Composition
Analysis before and after 30 and 60 days of treatment.
Parameters included:
Biodiversity (Observed Operational Taxonomic Units, OTUs).
Relative abundance of Lactobacillus genus and its species (L. crispatus, L. iners, etc.).
Relative amounts of pathogenic bacteria (Gardnerella vaginalis, Atopobium vaginae, etc.).
Measured: Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second month / end of treatment
Symptom improvement at intermediate time points
Comparison of VAS scores at Visit 1 (30 days) and Visit 2 (60 days) against baseline.
Measured: Baseline → Visit 1 (Day 30) Baseline → Visit 2 (Day 60)
Adverse Events Monitoring
Frequency and severity of side effects (e.g., redness, mild bleeding, burning, swelling) were recorded throughout the study.
Measured: Continuous from first laser session (Day 0) through 30 days and 60 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start1 Jun 2024
- Primary completion1 Oct 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vulva; AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is an interventional, single-center study. Patients will be randomized into two groups: one called the "control" group, in which patients will receive only the SmartXide2 treatment, and the second called "PALINGEN," in which patients will receive SmartXide2 treatment plus the application of Palingen cream. It should be noted that both SmartXide2 and Palingen cream (and their combination) have been part of the standard clinical practice at the experimental center for several years. The effectiveness of the combined action of the two treatments will be evaluated by analyzing the associated symptoms using a Visual Analogue Scale (VAS) from 1 to 10 for each symptom, as well as through analysis of the vaginal microbiome. Additionally, all adverse events will be recorded.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute for Social Security, Republic of San Marino
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, MAURIZIO FILIPPINI, Institute for Social Security, Republic of San Marino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07246616
- Sponsor's protocol ID
- MF-01-24 1
- Other IDs
- N/1
- Status last verified
- Jan 2026
- First submitted
- 17 Nov 2025
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mueck AO, Ruan X, Prasauskas V, Grob P, Ortmann O. Treatment of vaginal atrophy with estriol and lactobacilli combination: a clinical review. Climacteric. 2018 Apr;21(2):140-147. doi: 10.1080/13697137.2017.1421923. Epub 2018 Jan 30.
PubMed 29381086
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of CO₂ Laser Therapy Combined With Collagen Cream in Managing Vulvo-Vaginal Atrophy: A Randomized, Controlled Study on Symptom Relief and Microbiome Modulation
- ClinicalTrials.gov ID
- NCT07246616
- Acronym / sponsor ID
- MF-01-24 1
- Conditions
- Vulva; Atrophy
- Keywords
- Vulva, Atrophy, Co2, Vulvo-vaginal, Microbiome, Modulation, Laser, Theraphy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Institute for Social Security, Republic of San MarinoUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 1 Oct 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 24 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated a new treatment for postmenopausal women suffering from vulvo-vaginal atrophy (VVA), a condition that causes dryness, burning, and pain. Researchers tested whether combining CO₂ laser therapy with a collagen-based cream could improve symptoms more effectively than laser treatment alone.
Detailed description
Sixty women participated in the study. Results showed that the combination treatment provided greater relief from discomfort and helped restore vaginal health, with fewer side effects. This approach may offer a safe and effective alternative for women who cannot use hormone-based therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an interventional, single-center study. Patients will be randomized into two groups: one called the "control" group, in which patients will receive only the SmartXide2 treatment, and the second called "PALINGEN," in which patients will receive SmartXide2 treatment plus the application of Palingen cream. It should be noted that both SmartXide2 and Palingen cream (and their combination) have been part of the standard clinical practice at the experimental center for several years. The effectiveness of the combined action of the two treatments will be evaluated by analyzing the associated symptoms using a Visual Analogue Scale (VAS) from 1 to 10 for each symptom, as well as through analysis of the vaginal microbiome. Additionally, all adverse events will be recorded.
| Arm | Type | Receives |
|---|---|---|
| Laser Therapy Only (Control Group) | Active comparator | Device: SmartXide2 treatment plus the application of Palingen cream, Device: Laser Therapy Only (Control Group)Participants receive fractional CO₂ laser therapy according to the standard protocol for vulvo-vaginal atrophy. No additional topical treatment is applied. Laser sessions are performed at baseline (Day 0), Day 30, and Day 60. Follow-up visits include clinical evaluation and microbiome sampling at each time point. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Postmenopausal women with absence of menstrual cycle for at least 12 months, diagnosed with vulvovaginal atrophy (VVA) and presenting with related symptoms such as dryness, introital and deep dyspareunia, bleeding during intercourse, itching, or burning related to the severity of VVA, whether spontaneous or drug-induced (radio- or chemotherapy), either with a single symptom or a combination thereof.
- Age between 35 and 75 years;
- Patients unresponsive or dissatisfied with previous topical estrogen therapy, or presenting contraindications to the use of local and/or systemic estrogens.
- Previous negative Pap test performed within 3 years prior to study enrollment.
Key exclusion criteria (8 listed)
- • Pregnancy or breastfeeding;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SmartXide2 treatment plus the application of Palingen creamPatients will be randomized into two groups: one called the "control" group, in which patients will receive only the SmartXide2 treatment, and the second called "PALINGEN," in which patients will receive SmartXide2 treatment plus the application of Palingen cream. | Device | Laser Therapy Only (Control Group) |
| Laser Therapy Only (Control Group)Participants receive fractional CO₂ laser therapy according to the standard protocol for vulvo-vaginal atrophy. No additional topical treatment is applied. Laser sessions are performed at baseline (Day 0), Day 30, and Day 60. Follow-up visits include clinical evaluation and microbiome sampling at each time point. | Device | Laser Therapy Only (Control Group) |
Primary outcome
Improvement in VVA (Vulvo-Vaginal Atrophy) symptoms
Time frame: Outcome: Improvement in symptoms associated with vulvo-vaginal atrophy (VVA) Assessment Tool: Visual Analogue Scale (VAS) Time Frame: Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second
Assessed after 30 and 60 days of treatment using the Visual Analogue Scale (VAS). The VAS was used to quantify symptom intensity such as burning, dryness, itching, dyspareunia, and pain. Improvement was measured as the difference in VAS scores before and after treatment.
3 secondary outcomes
Vaginal Microbiome Composition
Time frame: Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second month / end of treatment
Symptom improvement at intermediate time points
Time frame: Baseline → Visit 1 (Day 30) Baseline → Visit 2 (Day 60)
Adverse Events Monitoring
Time frame: Continuous from first laser session (Day 0) through 30 days and 60 days post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Background: PubMed 29381086Mueck AO, Ruan X, Prasauskas V, Grob P, Ortmann O. Treatment of vaginal atrophy with estriol and lactobacilli combination: a clinical review. Climacteric. 2018 Apr;21(2):140-147. doi: 10.1080/13697137.2017.1421923. Epub 2018 Jan 30.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SmartXide2 treatment plus the application of Palingen cream in people with Vulva; Atrophy, run by Institute for Social Security, Republic of San Marino at 1 site in San Marino.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in San Marino. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in VVA (Vulvo-Vaginal Atrophy) symptoms (time frame: Outcome: Improvement in symptoms associated with vulvo-vaginal atrophy (VVA) Assessment Tool: Visual Analogue Scale (VAS) Time Frame: Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07246616, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.