Fractional CO2 Laser Therapy Versus 4% Topical Lidocaine Gel for Dyspareunia in Breast Cancer Survivors

Study Overview
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Brief Summary
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This trial seeks to determine if therapy with a CO2 laser to the vagina is more effective than lidocaine to the opening of the vagina before intercourse to reduce painful intercourse in women who are breast cancer survivors. This study will also be looking at whether or not the CO2 laser improves pelvic floor function, bowel and bladder function, and sexual function before and after treatment.

Detailed Description
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This is a randomized trial to determine the comparative effectiveness of the CO2RE laser device relative to topical lidocaine in treating dyspareunia among breast cancer survivors. The large and growing population of breast cancer survivors experience a significant burden of urogenital symptoms including dyspareunia. Several studies have evaluated the feasibility and effectiveness of CO2 lasers for the treatment of symptomatic vulvovaginal atrophy in postmenopausal women suggesting improvements in atrophy symptoms with favorable histological and microscopic changes. There is little know about the effectiveness of CO2 laser therapy in breast cancer survivors. Patients who are breast cancer survivors experiencing dyspareunia and desiring intervention will be randomized to two cohorts: (1) Treatment with the CO2RE laser or (2) application of 4% aqueous lidocaine applied to the vulvar vestibule for 3 minutes before vaginal penetration. The primary outcome will be the overall as well as lubrication, satisfaction, and pain domain scores on the Female Sexual Function Index instrument. Secondary outcomes will be according to other validated pain and pelvic floor symptom instruments. Following initiation of treatment, both groups will follow up at one-week, 1-month, 3-months, and 6-months. At the 3-month assessment, subjects in the lidocaine arm will be given the option to undergo CO2RE laser therapy. A combination of validated and non-validated physical exam and survey instruments will be utilized at each visit in order to assess pelvic floor function, bowel and bladder function, and sexual function before and after treatment.

Official Title
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Prospective Randomized Trial Comparing Treatment of Dyspareunia With Fractional CO2 Laser Therapy Versus 4% Topical Lidocaine Gel in the Setting of Breast Cancer Survivors.

Conditions
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Dyspareunia

Intervention / Treatment
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* Drug: 4% Topical Lidocaine Gel
* Device: CO2RE fractional laser therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects included must be female breast cancer survivors over the age of 18, sexually active (at least 4 episodes of sexual intercourse per month), and find intercourse painful. Subjects must also be English speaking and able to give informed consent. Exclusion Criteria: Subjects will be excluded if pregnant, has not had breast cancer, does not have painful intercourse secondary to treatment received for their breast cancer, is not English speaking, or lacks the ability to sign informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to two treatment cohorts (each with 35 patients): (1) treatment with the CO2RE laser or; (2) treatments of 4% aqueous lidocaine applied to the vulvar vestibule for 3 minutes before vaginal penetration. Both cohorts will have four follow-up assessments following initiation of treatment: (1) One-week post treatment initiation; (2) 1-month post treatment initiation; (3) 3-months post treatment initiation and; (4) 6-months post laser-only treatment initiation. At the 3-month assessment, subjects in the lidocaine arm will be allowed to try the CO2RE laser therapy. In doing this, an imbedded crossover trial is included that will allow assessment of subject decision-satisfaction between the two therapy approaches. The primary outcome will be the overall and lubrication, satisfaction, and pain domain scores on the Female Sexual Function Index instrument. Secondary outcomes will be other validated pain and pelvic floor symptom instruments.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CO2RE Laser<br>This group will undergo vaginal CO2 laser therapy for a total of three (3) treatments with one month between treatments. | Device: CO2RE fractional laser therapy<br>* This group will undergo vaginal CO2 laser therapy for a total of three (3) treatments with one month between treatments.<br>|
| Active Comparator: 4% Topical Lidocaine Gel<br>This group will be given 4% topical lidocaine gel to take home. The patient will apply the 4% lidocaine gel to the outside and opening of the vagina for 3 minutes before vaginal penetration. The patient will continue using the numbing gel prior to vaginal penetration for the extent of the study (3 months). | Drug: 4% Topical Lidocaine Gel<br>* This group will be given 4% topical lidocaine gel to take home. The patient will apply the 4% lidocaine gel to the outside and opening of the vagina for 3 minutes before vaginal penetration. The patient will continue using the numbing gel prior to vaginal penetration for the extent of the study (3 months).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Female Sexual Function Index (FSFI) score before and after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The Female Sexual Function Index (FSFI) is a survey instrument used to determine the level of sexual function or dysfunction in females. It is comprised of a 19 item questionnaire focused on sexual functioning. There are six domains assessed: desire, arousal, lubrication, orgasm, satisfaction, and pain. The subject is to consider each of the questions in the context of the previous 4 weeks. The scores of each of the domains are then calculated into a final score. Initial and follow-up assessments will allow comparisons across this instrument as well as all the secondary and other pre-specified outcome measures. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NPRS) score before and after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The Numeric Pain Rating Scale (NPRS) is a measure of pain intensity in adults.The NPRS is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of his/her pain. The common format is a horizontal bar or line. Similar to the VAS, the NPRS is anchored by terms describing pain severity extremes. The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable).The NPRS can be administered verbally (therefore also by telephone) or graphically for self-completion. Scores range from 0-10 with higher numbers representing higher pain intensity. | 9 months | 
| Incontinence Severity Index (ISI) score before and after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The Incontinence Severity Index (ISI) consists of two questions, regarding frequency and amount of leakage. It categorizes urinary incontinence (UI) into none, slight, moderate, severe, and very severe. It assess the frequency (from 0-4): (0-never, 1-less than once a month, 2-a few times a month, 3-a few times a week, 4-every day and/or night ), and amount (from 0-3) of urine leakage: 0-none, 1-drops, 2-small splashes, 3-more. The index value is from 0-12 obtained by multiplying the numbers responded in the two questions with categories of urinary incontinence severity of: None (0), Slight (1-2), Moderate (3-6), Severe (8-9), Very severe (12). | 9 months | 
| 3 Incontinence Questions (3-IQ) score before and after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The 3 Incontinence Questions (3-IQ) is a survey instrument that is used to determine if a patient has stress urinary incontinence (SUI), urge urinary incontinence (UUI), or mixed urinary incontinence (MUI). The subject is to consider each of the questions in the context of the previous 3 months.The first question asks if the patient has every leaked urine. The second question asks the patient to indicate if she has leaked urine with any of the following: activity, urge, or without activity or urge. The Third question asks which form of urinary leakage was most common. The response to question 3 is then used to determine if the patient has: 1) Stress only or mostly stress, 2) urge only or mostly urge, 3) other cause, or 4) mixed. | 9 months | 
| Colon Rectal Anal Distress Inventory (CRADI) score before and after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The Colon Rectal Anal Distress Inventory (CRADI) is a survey instrument used to determine the level and severity of bowel symptoms. It consists of 17 questions inquiring to specific questions regarding bowel symptoms. Total score out of 400, with higher scores indicating more bowel symptoms. | 9 months | 
| Patient Global Impression of Severity (PGI-S) score before treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The PGI-S are 1 question assessments of overall condition severity before implementation of therapy measured on a 7-point response scale. | 9 months | 
| Patient Global Impression of Improvement (PGI-I) score after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The Patient Global Impression of Improvement (PGI-I) is 1 question assessment of overall condition improvement since implementation of therapy measured on a 7-point response scale. | 9 months | 
| Satisfaction with Decision (SDS) score before and after treatment with topical lidocaine ointment or transvaginal CO2 laser among breast cancer survivors with dyspareunia. | The Satisfaction with Decision (SDS) was developed to measure patient satisfaction with health care decisions. The SDS is a 6-item questionnaire with a 5-point response scale with higher scores indicating higher overall satisfaction. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyspareunia, Laser, CO2, Breast Cancer, Vaginal Atrophy, Lidocaine