Methylene Blue Injection for Nonneoplastic Epithelial Disorders of Vulva

Study Overview
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Brief Summary
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The aim of this study is to demonstrate the safety and effectiveness of mixed methylene blue compound Injection for the treatment of nonneoplastic epithelial disorders（NNEDS） of vulva. NNEDS of skin and mucosa of vulva refer to a group of chronic diseases including squamous hyperplasia and lichen sclerosus, which mainly cause vulvar itching and hypopigmentation. Usually the itching is severe may influence social activities and sleep. In addition, NNEDS cause scarring of the vulva which may cause significant sexual dysfunction or pain. The reasons for NNEDs are not clear and the methods of treatment are diverse. The current treatments are primarily local drug (e.g. steroid, calcineurin inhibitors, immunosuppressive agents ), surgical treatments, laser or photodynamic therapy, and the gold standard treatment for lichen sclerosus is potent steroids creams. However, all the treatments are not good enough, and the diseases often recur and severely affect women's quality of life. So the investigators reviewed plenty of literatures, and found some authors used single intradermal 1% methylene blue injection for intractable idiopathic pruritus ani and the effect was good. As a preliminary experiment, the investigators used intradermal mixed methylene blue compound injection for a NNEDs patient in the year of 2012, the itching of the patient stopped immediately and the color of the vulva recovered 6 months later. The patient keeps healthy till now. And from then on, the investigators designed this study and to verify the effect and complications of intradermal mixed methylene blue compound injection for the treatment of NNEDS. So far, there is no similar study reported internationally.

Detailed Description
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Methylene blue compound injection are mixed by Methylene Blue injection, Dexamethasone powder-injection, Ropivacaine injection and Normal saline injection. Each individual component can help in a very wide range of medical conditions without serious side effects. In this study，the investigators used methylene blue compound injection intradermally to treat NNEDs patients. Patients with a diagnosis of biopsy proven NNEDs from Maternal and Child Health Hospital of Hubei Province (China) between October 2013 to October 2016 were recruited. Every patient received intradermal mixed methylene blue compound injection twice. All patients were observed during the hospitalization at the first injection, and two weeks later they received the second injection at the outpatient department. Ages, itching scores, percentage of hypopigmented skin, and recurrences were recorded through inquiry and physical examination before and after treatment. Side effects (such as edema, fever and vulva pain) were also recorded. All women were followed up 1, 3, 6, 12 months after treatment, which included inquiry and physical examination.

Official Title
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Evaluation of the Efficacy of Mixed Methylene Blue Compound Injection for the Treatment of Nonneoplastic Epithelial Disorders of Vulva.

Conditions
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Nonneoplastic Epithelial Disorders of Vulva

Intervention / Treatment
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* Drug: mixed methylene blue compound injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinically and biopsy confirmed non-neoplasia epithelial disorders of skin and mucosa of vulva. Patient must have a score of 5 or greater in the itching score table before treatment and the itching must last at least 6 months. Exclusion Criteria: Patients with vulvovaginal or other gynecological trauma, acute inflammatory diseases and other acute illness Patients have been treated with any kind of topical therapy at the vulva within 12 weeks prior to participation in the study Patients with other serious diseases (e.g. liver or kidney diseases) that need immediate treatment Patients with atypical vulvar hyperplasia or vulvar cancer confirmed by biopsy

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
Intervention Model: Single Group Assignment
Interventional Model Description: Pations with nonneoplastic epithelial disorders（NNEDS） of vulva.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>Methylene blue compound injection are mixed by Methylene Blue injection, Dexamethasone powder-injection, Ropivacaine injection and Normal saline injection. Each individual component can help in a very wide range of medical conditions without serious side effects. Every patient received intradermal mixed methylene blue compound injection twice. All patients were observed during the hospitalization at the first injection, and two weeks later they received the second injection at the outpatient department. | Drug: mixed methylene blue compound injection<br>* Every patient received intradermal mixed methylene blue compound injection twice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| itching scores | The patients rate the itching on a visual analogue scale (VAS) before and after the treatment. A VAS is a 100-mm long horizontal line with verbal descriptors at each end to express the extremes of the itching feeling. The most severe itching equals to score 10, and no itching equals to score 0. Patients marked the point on the line that best corresponded to their itching severity. | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of hypopigmented skin | Doctors rate the hypopigmented skin on a vulva surface area scale (VSAS) before and after treatment through colposcopy. The vulva area is divided into six regions as labia majora, labia minora, interlabial sulci, clitoris and clitoral hood, perineum, and perianal area. The investigators estimated that the area percentage of labia majora, labia minora, interlabial sulci, clitoris and clitoral hood, perineum, and perianal area was 48%, 24%, 4%, 4%, 10% and 10% differently. Among the six regions, interlabial sulci, clitoris and clitoral hood, perineum, and perianal area could be divided into four equal proportions at most when the area percentage was calculated. And each side of labia majora and labia minora could be divided into four equal proportions at most. If all the vulva area is involved, the VSAS score is 100%, and if no area of vulva is involed, the VSAS score is 0%. | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methylene blue, treatment, Nonneoplastic Epithelial Disorders