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Completed

NCT Number: NCT07246616

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

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.

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Key information

Age range

35 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

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

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • • 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.

Treatment and study plan

SmartXide2 treatment plus the application of Palingen cream

Device

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

    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.).

  2. Symptom improvement at intermediate time points

    Time frame: Baseline → Visit 1 (Day 30) Baseline → Visit 2 (Day 60)

    Comparison of VAS scores at Visit 1 (30 days) and Visit 2 (60 days) against baseline.

  3. Adverse Events Monitoring

    Time frame: Continuous from first laser session (Day 0) through 30 days and 60 days post-treatment

    Frequency and severity of side effects (e.g., redness, mild bleeding, burning, swelling) were recorded throughout the study.

Sponsors and collaborators

Lead sponsor

Institute for Social Security, Republic of San Marino

Other

Registry information

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Nov 24, 2025
Registry last updated
Jan 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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