Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Atrophy

Breast Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Breast Diseases

Skin Diseases

Pathological Conditions, Anatomical

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

All Drugs and Chemicals

Gastrointestinal Agents

Lipid Regulating Agents

Herbal and Botanical

Hormones

Betaine

Olive

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.

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.

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.

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.

C02 microablative laser

It is a moisturizing and regenerating gel whose active ingredients are olive oil, trimethylglycine and xylitol.

Regenerative topical treatment

Amalia Cañadas Molina

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 determine the prevalence and incidence of genitourinary syndrome in our population of patients diagnosed with breast cancer and who are undergoing adjuvant or neoadjuvant treatment (with the exception of chemotherapy).
* To assess the impact of genitourinary syndrome on the quality of life of these patients.
* To determine the degree of correlation between intensity of the symptomatology and impact on the quality of life of the same with the presence of characteristic changes of hormonal depletion at the tissue level and vaginal microbiota.
* To evaluate the safety and tolerability of the C02 laser in our group of patients. Special attention will be paid to the occurrence of adverse events that have not been described in the literature at the present time.
* Describe other effects of laser treatment on urinary symptoms that could serve as hypotheses for future studies.
* To evaluate the safety and tolerability of the topical non-hormonal regenerating agent XCM intim in our group of patients.
* To describe the effects of topical non-hormonal regenerative therapy on vulvo-vaginal and urinary symptoms and the impact on the quality of life of these patients.

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:

* Consult before treatment.
* First treatment visit (after acceptance and signing of the informed consent): First session of laser treatment and initiation of topical treatment.
* Second treatment visit (one month after the first session): Second session of laser treatment and topical treatment control.
* Third treatment visit (6 weeks after the second session): Third session of laser treatment and topical treatment control.
* Review 1.5 months after the 3rd session.
* Review 6 months after the 3rd session.
* Review 12 months after the 3rd session.
* Review 24 months after the 3rd session.

The tests and studies to be carried out during the study will be the following:

* Anamnesis (in all visits).
* Physical examination (at all visits).
* Gynecological ultrasound (in 1st visit, before starting treatment).
* Validated questionnaires (in all visits).
* Measurements of skin characteristics with cutometer (at all visits).
* Vaginal exudate (in first pretreatment visit, visit of the month and a half of finishing laser treatment, visit of the 6 months after finishing the laser treatment session, visit of the 12 months and visit of the 24 months).
* Vaginal mucosal biopsy (at the 1st visit before starting treatment and a month and a half after the third session).

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%, 60 patients in each group would be

A single-blind, randomized, controlled clinical trial is proposed, in which the patients included will be assigned to one of the three treatment arms.

In order to mask the patients from the treatment group to which they have been assigned, a simulated laser treatment session will be carried out in the case of patients belonging to the topical regenerative treatment group, which will consist of keeping the device turned off during it but faithfully reproducing both the duration as the sounds emitted by the device through recording previously made. In the case of patients assigned to laser treatment exclusively, they will be provided with a topical placebo (water-based), which must be applied with the same regimen as the emollient treatment under study.

A Laser and Topical Treatment Combination in the Vulvo-vaginal Atrophy Management in Breast Cancer Patients.

Effectiveness of C02 Microfractionated Laser in Conjunction With Topical Regenerative Therapy in the Management of Vulvo-vaginal Atrophy in Patients With a History of Breast Cancer. Randomized Experimental and Comparative Study.

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.

The tool used will be the Sexual Function-Vaginal Changes Questionnaire. Scores equal to or less than 24 points will result in an impact on quality of life. A rise of 3 or more points is considered a significant improvement.

The severity levels of quality of life impairment will be as follows:

* Mild (scores between 24 and 17)
* Moderate (scores between 16 and 8)
* Severe (scores between 7 and 1)

We will use the following measurement system:

Vulvar Health Index Score. It is based on the macroscopic inspection of the vulva performed through a colposcope. The scores range from 0 to 24, being higher to greater atrophy. It is considered a diagnosis of atrophy scores greater than 8 or having obtained 3 points in any of the items. The degrees of gravity are set as follows:

1. Between 9 and 14 points, mild
2. Between 15 and 20 points, moderate
3. Between 21 and 24 points, severe.

A reduction of 3 or more points in the overall score or at least one point will be considered a favorable response if there has been an item with a score of 3.

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.

The collection of the sample will consist of taking biopsy of vaginal mucosa using a 4 mm punch as an instrument.

Once obtained, the sample will be stained with hematoxylin-eosin and subjected to microscopic assessment.

The unit of measurement shall be in nanometers.

The collection of the samples will consist of taking biopsies of vaginal mucosa using a 4 mm punch as an instrument.

The sample will undergo the Schiff technique (PAS) and the number of stained cells will be determined.

The collection of samples will consist of taking biopsies of vaginal mucosa using a 4 mm punch as an instrument.

The immunohistochemical technique will be applied with antibodies against CD31 and a quantitative assessment of the number of capillaries / field of 40 increases will be carried out.

It will be measured through microbiological study. Samples shall be obtained by vaginal exudate.

The measurements will be made by WERFEN system and PCR technique.

It will be measured through microbiological study. Samples shall be obtained by vaginal exudate.

Free glycogen detection will be performed using a commercial kit.

It will be measured through microbiological study. Samples shall be obtained by vaginal exudate.

It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin.

The value will be given in the unit of measurement N / m².

It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin.

The value will be given in the unit of measurement g/h/m².

It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin.

The degree of pigmentation of the skin will be determined based on the concentration of melanin.

It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin.

To determine the degree of vascularization of the skin, specific wavelengths will be used, corresponding to the maximum level of spectral absorption of hemoglobin and avoiding other color influences (for example, bilirubin). The result corresponding will be immediately displayed in the form of index figures, on a scale of 0 - 999.

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.

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

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.

Lumenis Be Ltd.

Mucosa Innovations, S.L.

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

WO2085 is a hormone-free Moisturizing Cream and is used to treat "vulvovaginal dryness" symptoms.

Week 1: 2.5 g of the investigational product WO2085 Moisturising Cream will be applied intravaginally, once daily in the evening. In addition 0.5 g (1 fingertip unit) may be applied to the outer genital area as needed (also several times per day).

Week 2-4: The frequency may be reduced by the patient as needed. In addition 0.5 g (1 fingertip unit) may be applied to the outer genital area as needed (also several times per day).

WO2085 Moisturising Cream

Prof. Christoph Abels, MD, PhD

The aim of the study is to gain further experience with regard to the performance of the medical device WO2085 Moisturising Cream for breast cancer patients undergoing chemotherapy or treatment with anti-oestrogens / aromatase inhibitors

The goal of this application study was to answer the question as to whether the application of WO2085 Moisturising Cream for breast cancer patients undergoing chemotherapy or treatment with anti-oestrogens / aromatase inhibitors can result in an improvement in the subjective symptoms and objective diagnoses of vulvovaginal dryness while also ensuring good tolerability.

Investigation on the Efficacy of WO 2085 Moisturising Cream for Breast Cancer Patients Suffering From Vulvovaginal Dryness

Multicentric Study on the Application of WO 2085 Moisturising Cream for Breast Cancer Patients Suffering From the Symptoms of Vulvovaginal Dryness

Each symptom is rated according to severity on a scale from 0 to 4 (0=not present, 1=hardly pronounced, 2=moderately pronounced, 3=quite pronounced, 4=very pronounced)

The global judgement of efficacy will be assessed by the investigator and the patient according to the following scale: 1=very good to 6=unsatisfactory.

The global judgement of tolerability will be assessed by the investigator and the patient according to the following scale: 1=very good to 6=unsatisfactory.

Adverse events will be documented on Visit after 4 weeks (and in the patient diary, if applicable).

Dr. Dimitrios Chatsiproios

Dr. med. Klaus König

SAM®, Statistische Analysen und Monitoring GmbH

Dr. August Wolff GmbH & Co. KG Arzneimittel

Sexual Dysfunction, Physiological

Genital Diseases

Dermatologic Agents

Central Nervous System Depressants

Other Dietary Supplements

Psyllium

Calcium polycarbophil

Mineral Oil

Dehydroepiandrosterone

Hypnotics and Sedatives

DHEA (Dehydroepiandrosterone)

Passionflower

The hypnotic relaxation intervention consists of three different audio files, each about 20 minutes in length. These three hypnotic inductions build upon each other. The first hypnotic induction audio focuses on relaxation, feelings of wellness, wholeness, strength, and confidence. The second hypnotic induction audio focuses more specifically on body image related to sexuality and being a sexual being. The third hypnotic induction audio focuses on sexual desire, passion, and energy. Each hypnotic induction will be used for two weeks, three times per week for a total of six weeks of hypnosis.

The vaginal moisturizer component of this arm is the same as that described for the VVA study arm.

This study arm might best be described as standard of care. Vulvovaginal dryness will be treated with a daily moisturizer for two weeks, then every other day for the remaining six weeks. Vaginal moisturizer will be applied at night, before sleep and after all sexual activity. Several moisturizers are available, including vaginal DHEA (IntraRosa®). Due to the need for reproducibility, we have decided to use one non-hormonal vaginal moisturizer, Replens™ moisture, which is a vaginal moisturizer consisting primarily of a purified water, glycerin, and mineral oil. Other ingredients included in the formulation are polycarbophyl, carbomer, homopolymer type B, hydrogenated palm oil glyceride, sorbic acid, sodium hydroxide. The moisturizing gel was determined to be a medical device for marketing by the FDA in 2010. It is non-hormonal (unlike vaginal DHEA) and therefore will be more likely to be acceptable by a broader range of oncology providers.

HRI is a combination intervention (Replens™ vaginal moisturizer device and hypnotic relaxation behavioral intervention)

Hypnotic Relaxation Intervention (HRI)

VVA is a standard of care intervention (Replens™ vaginal moisturizer device)

Vulvovaginal Atrophy (VVA)

Debra L Barton, PhD,RN,FAAN

The overall objective of this program of research is to improve sexual health outcomes for women diagnosed with breast cancer. Our team is developing a multi-component intervention for the four key predictors of sexual health in female cancer survivors: self-image, vulvovaginal tissue quality and symptoms, desire/energy, and relationship-partner concerns. This proposal begins the proof-of-concept pilot study in women with a history of breast cancer to deliver a multi-component intervention to improve vulvo-vaginal atrophy with a vaginal moisturizer, and sexual energy and self-image with a mind-body intervention that involves relaxation and subconscious suggestions with a hypnotic induction delivered via audio file. The primary outcome will be to evaluate the feasibility and acceptability of a multi-component intervention for sexual function. It is hypothesized that at least eighty percent of randomized participants will complete the study without differential withdraws from the control group.

Women's Interventions for Sexual Health (WISH), is a two-arm randomized clinical trial to evaluate the feasibility and acceptability of a multi-component intervention addressing changes in body image, sexual desire, and vaginal dryness in thirty adult post-treatment breast cancer survivors. The study is eight weeks long and does not require any in-person visits. If a breast cancer survivor is determined eligible, they will be educated on the purpose, requirements, and procedures. If interested, they will be emailed the consent form and will schedule a virtual consent/baseline visit. After consent is obtained, the participant will be randomly assigned to a study arm, HRI (hypnotic relaxation intervention plus vaginal moisturizer) or VVA (vulvovaginal atrophy moisturizer only), given a study number, and educated on the use of Replens™ vaginal moisturizer. The participant will complete online surveys at the virtual baseline visit. Replens™ vaginal moisturizer will be sent to the participant's address and receipt of the moisturizer will be confirmed by study staff before the agreed upon week one start date. The participant will use the moisturizer every day during weeks one and two and every other day during weeks three through eight. Participants randomized to the HRI group will also receive an MP3 player with three hypnotic relaxation audio files and asked to complete a weekly practice log. Each hypnotic induction audio file will be used for two weeks, three times per week, for a total of six weeks of hypnosis. A second virtual visit will be held at two weeks to assess progress, adverse events and provide education to the HRI group. Check in phone calls will be scheduled for weeks four, six and eight. A link to online follow up surveys will be shared during weeks six and eight.

This is a two-arm, randomized clinical trial.

Women's Interventions for Sexual Health: WISH

Women's Interventions for Sexual Health: WISH, A Pilot Study

This is a small pilot study and as such, data will be thoroughly interrogated. However, if an investigator feels there are unanswered questions or wishes to add to a larger dataset, we would entertain all data sharing requests for deidentified data as appropriate.

The number of participants who consented divided by the number eligible

The number of participants who complete the 8 weeks of the study divided by the number who consented.

Breast Cancer Research Foundation

The University of Tennessee, Knoxville

McMahan-McKinley Endowed Professor of Gerontology

Infertility

Hot Flashes

Young breast cancer participants will receive their SCPR and access to additional web-based educational reproductive health information, including resource lists of helpful websites, followed by regular reproductive health prompts and study adherence reminders for 24 weeks.

Healthcare providers of young breast cancer participants randomized to the intervention arm will receive their patient's SCPR and access to the same additional web-based educational reproductive health information as their patient, including resource lists of helpful websites.

Young breast cancer participants randomized to the waitlist control arm will receive access to the web-based resources and study adherence reminders. At completion of the 24 weeks of follow up, they will have access to their SCPR.

Healthcare providers of young breast cancer participants randomized to the waitlist control arm will receive access to the same web-based resources as their patient.

The reproductive health survivorship care plan (SCPR) is a web-based educational tool that will include information on how to manage various reproductive health issues such as hot flashes, fertility concerns, contraception practices, and sexual function. The intervention also includes additional web-based information and resource lists, text-based reproductive health and study adherence prompts.

Reproductive Health Survivorship Care Plan (SCPR)

Web-based resource lists and text-based study adherence reminders

Control

H. Irene Su, MD MSCE

The investigators propose to test the efficacy of the Reproductive Health Survivorship Care Plan (SCP-R), a novel survivorship care tool to meet the reproductive health needs of young breast cancer survivors (YBCS). Most YBCS undergo chemotherapy and/or endocrine therapy, treatments that impair ovarian function and result in significant reproductive health late effects. These late effects include symptoms of estrogen deprivation such as hot flashes, fertility concerns, limited contraception options and sexual problems. Together they have a major, negative impact on quality of life.

Despite substantial research, treatment guidelines and clinical expertise on these issues, most YBCS and their healthcare providers have limited guidance on how best to manage these reproductive health late effects. The research team has generated a practical, accessible, evidence-based reproductive health survivorship care plan (the SCP-R) for YBCS and their providers to address this deficit in survivorship care. This clinical trial will test if YBCS who receive the web-based SCP-R are more likely than controls to improve on at least one of these reproductive health issues: hot flashes, sexual health, fertility concerns, and contraception.

Participants may be recruited from throughout the United States, as all study activities may be done remotely. It is not necessary to live in San Diego or visit UC San Diego to participate in the study.

YBCS who are interested in the study will be provided access to an online screening survey to determine eligibility. Eligible YBCS who consent to the study will be followed for 24 weeks.

Following a one-week study run in, YBCS participants will be randomized to the SCPR intervention or control arms and receive the corresponding interventions.

All YBCS participants will complete 3 study time points at enrollment, 12 and 24 weeks. At each time point, they will complete a web-based study questionnaire on medical and reproductive health. YBCS participants will also daily track their hot flashes via text messaging. YBCS participants will designate a healthcare provider with whom they would discuss reproductive health issues.

Designated healthcare providers will be approached to participate in the study. Those providers who enroll will complete 2 study assessments at weeks 0 and 24. At each study time point, HCP will be assessed for preparedness on managing reproductive health issues by a web-based questionnaire.

Reproductive Health Survivorship Care Plan

Intervening on Reproductive Health in Young Breast Cancer Survivors

Interested investigators may apply for deidentified data from this study

50% decrease in hot flash score. The hot flash score is calculated as the weighted sum of the number of hot flashes in each severity category multiplied by a severity-exclusive weight (1-mild, 2-moderate, 3-severe, 4-very severe). The minimum is 0 and there is no maximum. For example a woman can experience an unlimited number of hot flashes per day. Higher score indicates worse outcome.

Fertility concerns subscale score \<=3. Scores for the fertility subscale calculated by averaging responses (range 1-5) to the 3 subscale questions. The minimum score is 1, the maximum score is 5, Higher scores indicate worse outcome.

Use of World Health Organization Class I or II contraceptive methods (intrauterine devices, female sterilization, male partner sterilization, combined hormonal contraception, progestin implants or injections)

The Vulvovaginal Atrophy Score is a 4-item scale on vaginal dryness, soreness, irritation and dyspareunia experienced in the prior 4 weeks\]. Each item has a 4-point Likert scale response (0-none, 1-mild, 2-moderate, 3-severe). The scale is summarized by averaging responses, with higher scores indicating a greater level of vaginal atrophy.

University of California, San Diego

Professor of Obstetrics, Gynecology, and Reproductive Sciences

Young breast cancer participants will receive their SCPR and access to additional web-based educational reproductive health information, including resource lists of helpful websites, followed by regular reproductive health prompts and study adherence reminders for 24 weeks.

Reproductive Health Survivorship Care Plan (SCPR): The reproductive health survivorship care plan (SCPR) is a web-based educational tool that will include information on how to manage various reproductive health issues such as hot flashes, fertility concerns, contraception practices, and sexual function. The intervention also includes additional web-based information and resource lists, text-based reproductive health and study adherence prompts.

SCPR Intervention

Young breast cancer participants randomized to the waitlist control arm will receive access to the web-based resources and study adherence reminders. At completion of the 24 weeks of follow up, they will have access to their SCPR.

Control: Web-based resource lists and text-based study adherence reminders

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Irene Su, MD MSCE

Young breast cancer participants will receive their SCPR and access to additional web-based educational reproductive health information, including resource lists of helpful websites, followed by regular reproductive health prompts and study adherence reminders for 24 weeks.

Reproductive Health Survivorship Care Plan (SCPR): The reproductive health survivorship care plan (SCPR) is a web-based educational tool that will include information on how to manage various reproductive health issues such as hot flashes, fertility concerns, contraception practices, and sexual function. The intervention also includes additional web-based information and resource lists, text-based reproductive health and study adherence

Number of Participants With a 50% Decrease in Hot Flash Score

Number of Participants With the Reproductive Concerns After Cancer Scale - Fertility Concerns Subscale Score <=3

Number of Participants Using a WHO Class I or II Contraception

Number of Participants With a 50% Decrease in Vulvovaginal Atrophy Score

Young breast cancer participants will receive their SCPR and access to additional web-based educational reproductive health information, including resource lists of websites, followed by reproductive health prompts and study adherence reminders for 24 weeks.

Healthcare providers of young breast cancer participants randomized to the intervention arm will receive their patient's SCPR and access to the same additional web-based educational reproductive health information as their patient, including resource lists of helpful websites.

Reproductive Health Survivorship Care Plan (SCPR): The reproductive health survivorship care plan (SCPR) is a web-based educational tool that will include information on how to manage various reproductive health issues such as hot flashes, fertility concerns, contraception practices, and sexual function. The intervention also includes additional web-based information and resource lists, text-based reproductive health and study adherence prompts.

Young breast cancer participants randomized to the waitlist control arm will receive access to the web-based resources and study adherence reminders. At completion of the 24 weeks of follow up, they will have access to their SCPR.

Healthcare providers of young breast cancer participants randomized to the waitlist control arm will receive access to the same web-based resources as their patient.

Control: Web-based resource lists and text-based study adherence reminders

Healthcare Provider Preparedness Scale

Depression (PHQ-8)

Social Support (MOS Social Support)

Insomnia Scale

Female Sexual Function Inventory

Confidence for Managing Reproductive Health Issues Scale

Menopause Quality of Life (MENQOL)

Overall Study

Behaviors and Mental Disorders

Pruritus

Dyspareunia

Dysuria

Menopause

3 treatments approximately 4 weeks apart with vaginal/vulval laser

3 treatments approximately 4 weeks apart with "sham" laser

CO2 Fractional Ablative Laser

Placebo

Antonia Pearson, BMed

Emily Forward, MBBS MBA BSc

Antonia Pearson, BMed FRACP

Emily Forward, MBBS MBA Bsc

Gail Fischer, OAM FACD MD

Sally Baron-Hay, MBBS FRACP

Rebecca Stevenson

Nina Singh

Gavin Marx, MBBS FRACP

Andrew Booker, BMedFRANZCOG

To determine the efficacy of ablative carbon dioxide laser in the treatment of the signs and symptoms of vulvovaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) in women with breast cancer.

LAAVA 2 is a double blinded randomised placebo/sham-controlled trial assessing whether fractional ablative carbon dioxide is beneficial in improving symptoms in women with a history of early breast cancer. Patients will be randomly assigned in a 1:1 ratio to either active laser treatment or inactive "sham" laser treatment (setting of close to zero)

Participants will receive the 3 treatments approximately 4 weeks apart. Participants will then be followed up at twelve weeks post completion of treatment and twelve months post completion of treatment. At the twelve week follow up visit, after completion of study procedures, patients will be unblinded and those who received "sham" treatment will be allowed to crossover to "active" treatment if they wish.

Laser Therapy for Vulvovaginal Symptoms in Breast Cancer Patients

Improvement in vaginal dryness on a 10cm visual analog scale (VAS). A 10cm VAS is a scale from 0 to 10 with 0 being no symptoms and 10 being worst symptoms possible.

Improvement in itch, burning, dysuria, dyspareunia and urinary incontinence of a 10cm visual analog scale (VAS)

Improvement in maturation index from a vaginal swab (a pathological test: the maturation index counts 200 cells and compares the ratio of parabasal:intermediate:superficial squamous cells. Oestrogen deficient smears will show fewer superficial cells and an increase in parabasals (implies an atrophic picture)

)

Improvement in vaginal moistness, colour and labia stickiness (moistness and stickiness assessed by a physician as present or not, colour as assessed on a predefined colour chart out of 4 colours).

Improvement in QOL assessed on the Vulval Quality of Life Index (VQLI) -a validated tool. The scoring bands of the VQLI includes: 0-5 = no effect on patient's life, 6-13 = small effect on patient's life, 14-23 = moderate effect on patient's life, 24-37 = very large effect on patient's life, 38-45 = extremely large effect on patient's life.

Improvement in sexual function assessed on the Female Sexual Function Index (FSFI) - a validated tool

Patient satisfaction assessed on Likert Scale - a validated tool scoring from 1 to 5 (1=strongly disagree, 2=disagree, 3= neutral, 4=agree, 5=strongly agree)

Side effects reported over the duration of the study will be collected descriptively

Royal North Shore Hospital

Quality of Life

Two applications of HA gel (Mucogyne®) per week during one year.

Laser CO2 for vulvovaginal area during 2 sessions (15 min) at visits D0 and M6.

Injection of 1 mL of HA at D0 and M6 (DESIRIAL®).

Vaginal gel based on HA with liposomal structure applicated 2 times a week

Hyaluronique Acid Gel

The laser energy delivered along the vaginal wall heats the tissue without damaging it.

Laser CO2

HA injection performed under the mucosae (2-3mm in depth) following one injection point every 5mm on the 3 first cm of the vagina and on the posterior part of the introitus.

Hyaluronique Acid Injection

Barbara HERSANT, MD

Yazid BELKACEMI, MD, PhD

YAZID BELKACEMI

Many studies have shown that locoregional treatment (surgery, radiotherapy) and systemic treatment (endocrine therapy and chemotherapy) for breast cancer (BC) may impact sexuality by causing physical and/or psychological damages.

Approximately 50-75 % of BC survivors suffer from vulvovaginal atrophy (VVA). The earliest symptoms of VVA are decreased vaginal lubrication, followed by other vaginal and urinary symptoms, such as burning, itching, bleeding, leucorrhoea, dyspareunia and dysuria symptoms. Various surveys have shown that VVA symptoms lead to female sexual disorder and on their partners through sexual unsatisfactory. However, it appears that sexuality is a little discussed topic during the follow-up of BC survivors. Most of patients relate a poor satisfaction with information and counselling related to sexuality and vaginal health, which are denied by many practitioners.

Patients treated for BC cannot find relief in hormonal replacement therapy (HRT), which is considered the gold standard treatment for VVA symptoms. The usual treatments for these women are topics such as ovula or gel (lubricant, hyaluronic acid (HA)...) with however, a short term effect even when these topics are applied regularly and correctly during at least 2 to 3/weeks.In the literature, there is a significant impact on VVA at one month but later data are lacking . Moreover, patients' compliance and daily application are paramount of importance for efficacy that could disappear when the treatment is stopped.

No randomized controlled trial has compared this treatment to innovative strategies. In this context, it is important to establish management strategies for VVA and sexual disorder after BC.

Our objective is to assess prevalence rate of VVA among breast cancer survivors after the loco regional treatment and chemotherapy, and to compare the efficacy of innovative treatments namely, new biophysical inductor (Laser CO2) and chemical bio inductor (Hyaluronic acid injections) treatments to the efficacy of standard non-hormonal topic treatment for improving the VVA and the quality of sexual life on a long-term.

An open-label multicentre controlled trial randomized in 3 parallel groups (1:1:1) to assess the one-year superiority of bio physical inductor (C02 laser, D0 and M6, group laser) compared to the standard treatment currently recommended (Mucogyne, 2 times a week for one year, control group) in the one hand, and of chemical bio inductor (Desirial, injection of 1 mL of hyaluronic acid in the first 3 cm of the vaginal walls, D0 and M6, HA injection group) compared to the control group in the other hand in BC survivors with VVA, with blinded primary endpoint assessment.

The use of these innovative treatments (lasers and injections) for Vulvovaginal atrophy based on the bio induction and the regenerative medicine could improve the quality of the vaginal mucosa after breast cancer therapy and could be a new strategy for these women who cannot benefit from Hormone Replacement Therapy (HRT). The benefits expected are the improvement of the quality of vulvo-vaginal mucosa and the improvement of the sexual quality of life of the patient.

An open-label multicentre controlled trial randomized in 3 parallel groups (1:1:1) :

* Bio physical inductor : CO2 laser
* Standard treatment : Hyaluronic Acid gel
* Chemical bio inductor : injection of Hyaluronic Acid

According to the center's organization, an operator and an investigator-evaluator will be identified for each patient or for all patients.

Evaluation of Innovative Therapeutic Approaches of Vaginal and Sexual Dysfunction After Breast Cancer Treatment

Prospective Evaluation of Innovative Therapeutic Approaches of Vaginal and Sexual Dysfunction After Breast Cancer Treatment : a Randomized Multicenter Controlled Trial

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Laser and Topical Treatment Combination in the Vulvo-vaginal Atrophy Management in Breast Cancer Patients.	NCT05585476	Female Urogenit... Breast Cancer F...	C02 microablati... Regenerative to...	18 Years - 100 Years	Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Investigation on the Efficacy of WO 2085 Moisturising Cream for Breast Cancer Patients Suffering From Vulvovaginal Dryness	NCT03593122	Vulvovaginal At...	WO2085 Moisturi...	18 Years -	Dr. August Wolff GmbH & Co. KG Arzneimittel
Women's Interventions for Sexual Health: WISH	NCT05692960	Sexual Dysfunct... Body Image Libido; Loss, A...	Hypnotic Relaxa... Vulvovaginal At...	18 Years - 99 Years	The University of Tennessee, Knoxville
Investigation on the Efficacy of WO 2085 Moisturising Cream for Breast Cancer Patients Suffering From Vulvovaginal Dryness	NCT03593122	Vulvovaginal At...	WO2085 Moisturi...	18 Years -	Dr. August Wolff GmbH & Co. KG Arzneimittel
Reproductive Health Survivorship Care Plan	NCT02667626	Breast Cancer Hot Flashes Sexual Dysfunct... Fertility Contraception	Reproductive He... Control	18 Years - 45 Years	University of California, San Diego
Laser Therapy for Vulvovaginal Symptoms in Breast Cancer Patients	NCT03628092	Vulvovaginal At... Genitourinary S...	CO2 Fractional ... Placebo	18 Years -	Royal North Shore Hospital
Evaluation of Innovative Therapeutic Approaches of Vaginal and Sexual Dysfunction After Breast Cancer Treatment	NCT04713917	Breast Cancer	Hyaluronique Ac... Laser CO2 Hyaluronique Ac...	18 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
LASER and Radiofrequency for Treatment of Vaginal Vulvar Atrophy (VVA) in Women Treated for Breast Cancer (EPMLARF-arm2)	NCT04081805	Vaginal Atrophy Vulva; Atrophy Breast Cancer	LASER Micro Ablative ... Promestriene	30 Years - 75 Years	Federal University of São Paulo

Spots Global Cancer Trial Database for vulvovaginal atrophy