Novel Topical Therapies for the Treatment of Genital Pain

Study Overview
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Brief Summary
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This study is testing drugs not previously used topically for the treatment of vulvodynia, a common genital pain syndrome. It is hoped that one of these drugs will improve vaginal entryway pain with touch, daily pain scores and sexual functioning.

Detailed Description
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Vulvodynia is defined as burning pain, occurring in the absence of any visible finding or a clinically identifiable nervous disorder. Current treatments include vulvar care measure, topical medications, oral medications, biofeedback, physical therapy and surgery. The usual treatment is to have the patient take either tricyclic antidepressants or anti convulsants orally, however these methods seldom bring total relief. These drugs do have significant side effects limiting the patient's tolerance of the higher does sometimes needed. An effective topical medication would greatly benefit these women with fewer side effects and better tolerance. Topical amitriptyline and baclofen are often prescribed, but no studies have been done to support their use. Topical gabapentin has also been shown to have good effect, but no prospective clinical study as been done. This study will test topical application of Cetaphil, Loperamide, Gabapentin, Ketoprofen, Ketamine and Amitriptyline over a 19 week period in the first phase of the study. The drugs are compounded by the University of Rochester research pharmacy and dispensed in 19 vials, one vial to be used each week. Patients and study personnel are blinded as to which drug is being used. Each study participant was given a week of placebo at the initiation of the study. Each study compound, which contains both the drug and the base (Cetaphil) will be used twice a day for two weeks in a row, followed by a one week washout of base alone. If a patient finds that one of the drugs is effective she may stop participation after the first 13 weeks and request that the most effective drug be prescribed for her. The unblinding officer would then work with the research pharmacy to identify the effective drug and provide the patient with a prescription for that drug. If the patient desires, she may enroll in the second phase of the study when she will test the last two drugs over a six week period with the washout as in the first segment of the study. The drugs would be administered in vials as in the first section of the study. Every week on Sunday the patient will complete an electronic diary, recording her daily pain, any drug side effects, pain with the tampon test and overall health. Every three weeks she will complete the Female Sexual Function Index on the same electronic system. She would start her new drug on Monday each week. Additionally the coordinator of the study will call each patient on Wednesday to see if they are having any problems with the drug started on Monday. All patients who could become pregnant are required to maintain effective contraception throughout the study.

Official Title
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Novel Topical Therapies for the Treatment of Genital Pain

Conditions
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Female Genital Diseases

Intervention / Treatment
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* Drug: Amitriptyline
* Drug: Baclofen
* Drug: Ketoprofen
* Drug: Ketamine
* Drug: Loperamide
* Drug: Gabapentin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women between ages of 18 and 65 who complain of localized provoked vulvar pain and meet the criteria for the diagnosis of localized provoked vulvodynia. Patients who have failed or have been unable to tolerate previous attempts at systematic therapy or surgery will be specifically recruited. Exclusion Criteria: The presence of a dermatologic or neurologic condition which is determined by the investigator to be the primary cause of the patient's pain. Allergy to any of the medications or the base itself. Concurrent use of the following medications. . The patient may enroll in the study after a two week washout from these medications. Patients may need to receive approval from the prescribing physician before stopping these medications. Failure to obtain approval for medication cessation would be cause for exclusion. Gabapentin (NeurontinTM) Amitriptyline (ElavilTM) Nortriptyline (PamelorTM) Desipramine (NorpraminTM) Tramadol (UltramTM, ConZipTM, RybixTM, RysoltTM, Ultram ERTM) Pregabalin (LyricaTM) Baclofen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medications<br>Each study subject will be sequentially exposed to each of the study drugs and the placebo in a random order. The study is designed as a double blinded, crossover study. | Drug: Amitriptyline<br>* Topical application of the drug at a 2% concentration in combination with 2% Baclofen<br>* Other names: Elavil;Drug: Baclofen<br>* Used topically at 2% concentration in combination with 2% amitriptyline<br>* Other names: Lioresal;Drug: Ketoprofen<br>* To be applied topically at a 10% concentration<br>* Other names: Orudis KT;Drug: Ketamine<br>* To be applied topically at a 10% concentration<br>* Other names: Ketalar;Drug: Loperamide<br>* To be applied topically at a 5% concentration<br>* Other names: Kaopectate;Drug: Gabapentin<br>* To be applied topically at a 6% concentration<br>* Other names: Neurontin;|
| Placebo Comparator: Placebo<br>The compounding base alone will be used as a placebo. Each participant will be given each drug and the placebo sequentially in random order. | Drug: placebo<br>* Compounding base to be used alone as a placebo<br>* Other names: Cetaphil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Daily Genital Pain. | Each subject was asked to keep a symptom diary recording her daily genital pain, measured on a 10 point Likert scale. A score of 0 was defined as no pain and a score of 10 was defined as worst imaginable pain. These daily values were collected and a mean pain score for the period of treatment was calculated. | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Tampon Test Pain | Reduction in the pain, as measured on a 10 point Likert scale, associated with the insertion and removal of a tampon. This is a validated surrogate for pain associated with intercourse. Subjects were asked to insert and remove a tampon each week and report the degree of pain associated with this. A score of 0 was defined as no pain, and a score of 10 was defined as worst imaginable pain. | 13 weeks |