An interventional study of C02 microablative laser and Regenerative topical treatment in Female Urogenital Diseases and Breast Cancer Female, sponsored by Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz. Recruiting at 1 site in Spain. Open to female participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz · Not applicable, Interventional, and Treatment
The genito-urinary syndrome of menopause severely affects patients with a history of gynecological cancer, especially those diagnosed with breast cancer. At the present time, we do not have solid scientific evidence on treatments that can be effective and safe to address this pathology. Based on the above, we have developed our working hypothesis where it is postulated that the microfractionated laser treatment of C02, in conjunction with topical regenerative treatment, constitute an effective alternative in the management of vulvo-vaginal atrophy in oncological patients who have contraindicated hormonal treatments.
Based on the hypothesis set out in the previous section, the main objective of the study will consist of:
-To assess the effectiveness of microfractionated C02 laser therapy in combination with non-hormonal topical regenerative therapy versus laser treatment or non-hormonal topical regenerative treatment (the latter two exclusively) in the management of symptoms derived from vulvovaginal atrophy in cancer patients who are contraindicated to the use of hormonal therapies.
As secondary objectives we have the following:
To carry out all the above, it is proposed to perform a controlled and randomized clinical trial, single blind, in which the patients included will be assigned to one of the 3 existing treatment arms and that we will explain in detail in later sections.
Recruitment is planned to begin in December 2022. The overall duration of the study is estimated at approximately 42 months, from the beginning of the recruitment period to the last follow-up visit. This study is intended to be conducted from December 2022 to January 2026.
All those patients who meet the inclusion criteria and do not present any reason for exclusion will be given the informative document on the study. If they agree to participate, they will deliver said signed document and will be recruited and randomized in a single-blind manner (only the participant), in a 1:1:1 ratio to laser treatment + regenerative topical treatment or to regenerative topical treatment or to laser treatment ( latter 2 in exclusivity). The entire process of selection, inclusion and randomization will be supervised by both the Research Institute and the Clinical Research Ethics Committee of the Jiménez Díaz Foundation, which will carry out regular audits.
The study will be conducted in accordance with the protocol and standards of good clinical practice, as described in: Harmonized Tripartite Standards of ICH E6, for Good Clinical Practice 1996. Law 14/2007 on Biomedical Research Directive 2001/20/EC. Updated Declaration of Helsinki and amendments concerning medical research on human beings. The researcher agrees, with the signing of this protocol, to follow the instructions and procedures described therein and therefore will comply with the principles of Good Clinical Practice on which it is based. Once the protocol has been signed, it should not be modified without the written agreement of both the sponsor and the principal investigator, and with the consent of the Clinical Trials Ethics Committee.
All the information collected will be treated in a strictly confidential manner, in accordance with current regulations (Regulation (EU) 2016/679 of the European Parliament and of the Council, of April 27, 2016 (GDPR), Law 41/2002 on Patient Autonomy, Law 14/1986 General Health and Law 14/2007 on Biomedical Research). The patient will have the right to access, modify, oppose and cancel their data. In addition, they can limit the processing of data that are incorrect, request a copy or transfer to a third party (portability) the data that has been provided for the study. To exercise their rights, the patient must contact the principal investigator of the study. Data cannot be deleted even if the patient stops participating in the trial to ensure the validity of the research and comply with legal duties and drug authorization requirements. Likewise, the patient has the right to contact the Data Protection Agency if they are not satisfied.
It is the investigator's responsibility to document all adverse events that occur during the clinical trial. At each visit/assessment, all adverse events observed by both the investigator and one of his or her clinical collaborators, as well as those reported by the subject spontaneously or in response to a direct question, shall be evaluated by the investigator and noted in the adverse events section of the subject's data collection notebook.
The nature of each event, the time of onset after the intervention, the duration, the severity and relationship to the intervention should be established. The details of its handling must be recorded on the corresponding pages of the data collection notebook. The initial symptomatology should be well documented at the screening visit. It is important to correctly collect the baseline information in order to interpret the data of the following visits.
Investigators should follow up on subjects with adverse events until they have subsided, disappeared, or until the process has stabilized. Reports on the course of the subject's evolution should be sent to the monitor of the clinical trial.
The principal investigator shall report serious and unexpected adverse events to the sponsor by telephone or fax within 24 hours of becoming aware of the adverse event by the investigator, who shall in turn inform the health authorities. The previous report made by telephone or fax shall be followed by a complete report including a copy of the relevant data collected or recorded at the centre or other documents that occur as a result of the adverse event.
The total number of visits for patients in both treatment arms will be 8, leaving the study schedule as follows:
The tests and studies to be carried out during the study will be the following:
A digital data collection notebook will be created by the company Xolomon ® to guarantee the quality and reliability of the information. All data will be entered 2 times by 2 different researchers between whom there will be no contact. In the event that there is a discrepancy in the same field, the computer system will send an alert to the main researcher and he will be in charge of clarifying where the error is. Likewise, it will be the principal investigator who verifies the integrity, accuracy and veracity of the data entered, by comparing them with those collected in the clinical history of patient care.
All variables entered in the digital data notebook will have masks, ranges of values and dictionaries depending on the type of variable and the content they must integrate.
Regarding the statistical analysis of the data, a description of the characteristics of the patients will be made. Qualitative variables will be described by frequencies and percentages. The quantitative variables will be described by the mean and the standard deviation, or by the median and the interquartile range, depending on the degree of symmetry presented by the distribution of the data. Comparisons between the two treatment groups referring to the qualitative variables will be made by the Chi-square test, or failing that by Fisher's exact test. In the case of quantitative variables, comparisons will be made by Student's t test, or by Wilcoxon range test, depending on whether or not the data follow a normal distribution. To test normality, the Shapiro-Wilk test will be used. Whenever possible, the difference between the two treatment groups will be quantified, along with their 95% confidence intervals. The treatment of the lost values will be carried out through the Multiple Imputation method, for which, sets of databases will be generated from the original database, which will contain imputed values based on a random selection. The statistical analyses will be carried out by the Biostatistics service of the Jiménez Díaz Foundation University Hospital, through the Statistical Program Stata 14.0.
The sample size has been calculated in order to detect a difference of 2 points, between the means of the symptom intensity scale of the three groups. A maximum standard deviation of 3 points and a loss percentage of 10% are assumed. Under these assumptions, if we set the significance level at 5% and statistical power at 90%, 65 patients in each group would be
Patients must meet ALL of the following criteria to be included in the study:
Exclusion Criteria:
Patients who present ANY of the following criteria may not be selected to participate in this study:
The treatments used in this arm are the following: 1. º Microfractionated laser treatment of C02, through the AcupulseDuo generator of the company Lumenis®. The treatment regimen would consist of three sessions in total with periodicity of 4 weeks, between the first and the second, and 6 weeks between the second and third. The application of laser energy will be carried out by vaginal and vulvar terminals. The dose applied will consist of monopulse shots distributed throughout the vaginal mucosa and vulvar skin of 10 mJ of energy and at a density of 10%. 2. nd Topical treatment: It consists of the application of XCM® intim of the company Mucosa Innovations. The route of administration would be vulvo-vaginal. The dose applied would be 2 ml of total product every 12 hours during 36 months.
Device: C02 microablative laser · Combination Product: Regenerative topical treatment
In this arm, only the regenerative treatment of XCM® intim of the company Mucosa Innovations will be used. The route of administration would be vulvo-vaginal. The dose applied would be 2 ml of total product every 12 hours. The total duration of treatment would be 36 months.
Combination Product: Regenerative topical treatment
The treatments used in this arm are the following: 1. º Microfractionated laser treatment of C02, through the AcupulseDuo generator of the company Lumenis®. The treatment regimen would consist of three sessions in total with periodicity of 4 weeks, between the first and the second, and 6 weeks between the second and third. The application of laser energy will be carried out by vaginal and vulvar terminals. The dose applied will consist of monopulse shots distributed throughout the vaginal mucosa and vulvar skin of 10 mJ of energy and at a density of 10%. 2. ºPlacebo vulvo-vaginal topical gel, consisting of a watery base.
Device: C02 microablative laser
The C02 microablative laser was the first to be used in the treatment of menopausal genitourinary syndrome. Its mechanism of action is based on the emission of light at a wavelength of 10600nm that is absorbed by the water molecules contained in the vaginal mucosa, leading to local remodeling of connective tissue and neoformation of collagen, elastic fibers and other components of the extracellular matrix.
It is a moisturizing and regenerating gel whose active ingredients are olive oil, trimethylglycine and xylitol.
Presence of symptoms at the vulvovaginal level and their intensity
This group will include the following items: * Pain with sexual intercourse (dyspareunia). * Feeling of vaginal stiffness. * Dryness. * Vulvar itching. * Vulvar and/or vaginal burning. * Urinary frequency (more than 8 times a day). * Burning when urinating (dysuria). The way to measure the intensity of these symptoms will be through Visual Analog Scale Of Symptom Intensity, with absolute values ranging from 0 to 10. We will consider improvement a reduction of 2 or more points in at least 50% of the items. Meeting only this item is already considered an efficacy criterion.
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Impact in the quality of life of vulvo-vaginal symptoms.
The tool used will be the Day-to-Day impact of Vaginal Aging (DIVA) Questionnaire. This questionnaire covers four domains: * Activities of daily living * Sexual activity * Emotional well-being * Self-concept and body image Each domain, in turn, consists of several questions. The score for each domain is calculated as the mean of the scores obtained for the questions comprising that domain. The total questionnaire score is, in turn, calculated as the mean of the scores for each domain. Therefore, the total score ranges from 0 to 4 points. The categories assigned to each score value are as follows: 0 = No impairment 1. = Minimal impairment 2. = Moderate impairment 3. = Considerable impairment 4. = Extreme impairment A reduction of at least one point in the final score will be considered a clinically significant improvement.
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Changes in vaginal physical examination
We will use the following measurement systems: Vaginal Health Index Score. It is based on the macroscopic inspection of the vagina performed through a colposcope. Scores range from 5 to 25 points (scores equal to or less than 15 are considered diagnostic of atrophy). It is carried out by assessing different items related to exploratory findings. We can categorize the scores into different degrees of severity of vulvo-vaginal atrophy objectified to the examination: 1. \>from 15 points, absence of atrophy 2. Between 15 and 13 points, mild 3. Between 12 and 9 points, moderate 4. Between 8 and 5 points, severe An increase of 2 or more points in the overall score will be considered a favourable response.
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Histological Changes in Vaginal Mucosa
Samples will be collected by obtaining vaginal mucosal biopsies using a 4-mm punch biopsy instrument. The histological assessment will include the following: Hematoxylin and eosin (H\&E) staining: overall assessment of the sample and measurement, in micrometers, of the vaginal mucosal epithelial thickness. Vaginal Maturation Index (VMI): percentage of superficial, intermediate, and parabasal epithelial cells. Periodic Acid-Schiff (PAS) staining: quantification of cellular glycogen and qualitative assessment of the degree of hyalinization on a 0-3 scale. Orcein staining: qualitative assessment of the density of elastic fibers on a 0-3 scale. Collagen quantification using Masson's trichrome staining. The immunohistochemical assessment will include: CD31: quantitative assessment of the number of capillaries per ×40 microscopic field. Three measurements will be performed in the most representative fields, and the mean value will be calculated.
Time frame: At baseline (first study visit) and 6 weeks after completion of treatment.
Microbiological Assessment of the Vaginal Ecosystem
Samples will be collected by obtaining vaginal swabs. The following assessments will be performed: * Microscopic examination for the diagnosis of bacterial vaginosis. * Molecular identification by PCR and MALDI-TOF analysis of isolated colonies of: Lactobacilli, including differentiation of: Lactobacillus crispatus Lactobacillus jensenii Lactobacillus gasseri Candida spp. Gardnerella vaginalis --\>Measurement of the pH of the sample
Time frame: At baseline (first study visit) and 6 weeks after completion of treatment.
Vulvar Skin Characteristics
Various measurements of vulvar skin will be obtained using the Soft Plus skin analyzer (Callegari). The following characteristics will be assessed: * Elasticity. The value will be given in the unit of measurement N / m². * Hydration. The value will be given in the unit of measurement g/h/m². * Hydration. The values will be reported categorically using the following items: none, mild, moderate, and severe.
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Presence of bladder hyperactivity clinic
The following questionnaires will be used: Bladder control self-assessment questionnaire. This scale measures 2 items: Presence of symptoms and discomfort generated by them. The range of values for each of them goes from 0 to 12, with the severity levels being the following in both cases: 0--\>Absence of symptoms/discomfort. 1-3--\>Mild symptoms/discomfort. 4-6--\>Moderate symptoms/discomfort. 7-9--\>Severe symptoms/discomfort. 10-12--\>Very serious symptoms/discomfort.
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Presence of urinary incontinence
The Sandvik Test will be used. It consists of 2 sections whose scores are multiplied. The range of scores goes from 0 to 12, with the only possible values being 0, 1, 2, 3, 4, 6, 8, 9 and 12. The degree of urinary incontinence shall be classified as follows: 0--\>Absence of incontinence 1-2--\>Mild urinary incontinence 3-6--\>Moderate urinary incontinence 8-9--\>Severe urinary incontinence 12--\>Very severe urinary incontinence
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Impact of urinary incontinence on quality of life
We will use the International Consultation on Incontinence Questionnaire-Short Form. Of this scale we will only use in section that measures the degree of discomfort caused by incontinence and that reaches the values of 1 to 10.
Time frame: From prior consultation at the beginning of treatment to 6 months after it ends.
Plan to share: No
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Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz