Topicals: Novel Topical Therapies for the Treatment of Genital Pain

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT02099006
• Collaborator: Mae Stone Goode Foundation (Other)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 19
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Female Genital Diseases	Drug: Amitriptyline; Drug: Baclofen; Drug: Ketoprofen; Drug: Ketamine; Drug: Loperamide; Drug: Gabapentin; Drug: placebo	Phase 2/Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Novel Topical Therapies for the Treatment of Genital Pain
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Medications 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; Topical application of the drug at a 2% concentration in combination with 2% Baclofen; Other Names: Elavil ; Drug: Baclofen; Used topically at 2% concentration in combination with 2% amitriptyline; Other Names: Lioresal ; Drug: Ketoprofen; To be applied topically at a 10% concentration; Other Names: Orudis Oruvail Nexcede Orudis KT ; Drug: Ketamine; To be applied topically at a 10% concentration; Other Names: Ketalar ; Drug: Loperamide; To be applied topically at a 5% concentration; Other Names: Imodium Imotil Kaopectate ; Drug: Gabapentin; To be applied topically at a 6% concentration; Other Names: Neurontin
Placebo Comparator: Placebo 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; Compounding base to be used alone as a placebo; Other Names: Cetaphil

Outcome Measures

Primary Outcome Measures

1. Reduction in Daily Genital Pain. [13 weeks]

   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.

Secondary Outcome Measures

1. Reduction in Tampon Test Pain [13 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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:

1. The presence of a dermatologic or neurologic condition which is determined by the investigator to be the primary cause of the patient's pain.

2. Allergy to any of the medications or the base itself.

3. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Rochester	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester
• Mae Stone Goode Foundation

Investigators

• Principal Investigator: Adrienne D Bonham, MD, University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adrienne Bonham, Associate Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT02099006
• Other Study ID Numbers: 46905
• First Posted: Mar 28, 2014
• Last Update Posted: Jul 15, 2016
• Last Verified: Jul 1, 2016

• Additional relevant MeSH terms: Ketoprofen; Ketamine; Gabapentin; Amitriptyline; Baclofen; Loperamide; Antidiarrheals

Study Results

Participant Flow

Arm/Group Title	All Study Participants
Arm/Group Description	Each study subject was 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. Amitriptyline 2%/ Baclofen 2%: Topical application of the drug at a 2% concentration in combination with 2% Baclofen Ketoprofen: To be applied topically at a 10% concentration Ketamine: To be applied topically at a 10% concentration Loperamide: To be applied topically at a 5% concentration Gabapentin: To be applied topically at a 6% concentration
Period Title: Overall Study
STARTED	9
Received Placebo	9
Received Amitriptyline/ Baclofen	7
Received Ketoprofen	3
Received Loperamide	7
Received Ketamine	6
Received Gabapentin	8
COMPLETED	8
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	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. Amitriptyline/ Baclofen: Topical application of the drug at a 2% concentration in combination with 2% Baclofen Ketoprofen: To be applied topically at a 10% concentration Ketamine: To be applied topically at a 10% concentration Loperamide: To be applied topically at a 5% concentration Gabapentin: To be applied topically at a 6% concentration
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	9 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Reduction in Daily Genital Pain.
Description	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.
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

For each placebo entry the data is limited to include only those participates who also received the named intervention.

Arm/Group Title	Medications	Placebo
Arm/Group Description	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. Amitriptyline: Topical application of the drug at a 2% concentration in combination with 2% Baclofen Baclofen: Used topically at 2% concentration in combination with 2% amitriptyline Ketoprofen: To be applied topically at a 10% concentration Ketamine: To be applied topically at a 10% concentration Loperamide: To be applied topically at a 5% concentration Gabapentin: To be applied topically at a 6% concentration	The compounding base alone will be used as a placebo. Each participant will be given each drug and the placebo sequentially in random order. placebo: Compounding base to be used alone as a placebo
Measure Participants	9	9
Loperamide	2.4 (1.94)	2.92 (2.3)
Ketamine	3.42 (2.45)	2.77 (2.46)
Gabapentin	3.70 (2.92)	3.41 (2.55)
amtriptyline/baclofen	3.87 (2.74)	3.61 (2.68)
ketoprofen	5.05 (3.34)	5.05 (3.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in daily genital pain would be no different with the daily application of loperamide than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	t-test, 2 sided
	Comments	Paired T test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in daily genital pain would be no different with the daily application of ketamine than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	t-test, 2 sided
	Comments	Paired

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in daily genital pain would be no different with the daily application of gabapentin than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	t-test, 2 sided
	Comments	paired

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in daily genital pain would be no different with the daily application of amitriptyline and baclofen than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	t-test, 2 sided
	Comments	Paired

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in daily genital pain would be no different with the daily application of ketoprofen than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	t-test, 2 sided
	Comments	Paired

2. Secondary Outcome

Title	Reduction in Tampon Test Pain
Description	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.
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

For each placebo entry the data is limited to include only those participates who also received the named intervention.

Arm/Group Title	Medications	Placebo
Arm/Group Description	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. Amitriptyline: Topical application of the drug at a 2% concentration in combination with 2% Baclofen Baclofen: Used topically at 2% concentration in combination with 2% amitriptyline Ketoprofen: To be applied topically at a 10% concentration Ketamine: To be applied topically at a 10% concentration Loperamide: To be applied topically at a 5% concentration Gabapentin: To be applied topically at a 6% concentration	The compounding base alone will be used as a placebo. Each participant will be given each drug and the placebo sequentially in random order. placebo: Compounding base to be used alone as a placebo
Measure Participants	9	9
loperamide	4.71 (2.75)	5.29 (3.21)
ketamine	5.92 (3.56)	5.92 (3.00)
gabapentin	5.125 (3.57)	4.875 (3.19)
ketoprofen	6.17 (3.18)	6.0 (3.46)
amitriptyline/baclofen	5.43 (2.75)	5.36 (3.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in tampon test pain would be no different with the daily application of loperamide cream than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	t-test, 2 sided
	Comments	paired

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in tampon test pain would be no different with the daily application of ketamine cream than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	t-test, 2 sided
	Comments	Paired

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in tampon test pain would be no different with the daily application of gabapentin cream than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	t-test, 2 sided
	Comments	Paired

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in tampon test pain would be no different with the daily application of ketoprofen cream than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	t-test, 2 sided
	Comments	Paired

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Medications, Placebo
	Comments	Null hypothesis - that the improvement in tampon test pain would be no different with the daily application of amitriptyline/baclofen cream than with the daily application of a placebo cream.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	t-test, 2 sided
	Comments	Paired

Adverse Events

Time Frame	1.5 years
Arm/Group Title	Medications		Placebo
Arm/Group Description	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. Amitriptyline: Topical application of the drug at a 2% concentration in combination with 2% Baclofen Baclofen: Used topically at 2% concentration in combination with 2% amitriptyline Ketoprofen: To be applied topically at a 10% concentration Ketamine: To be applied topically at a 10% concentration Loperamide: To be applied topically at a 5% concentration Gabapentin: To be applied topically at a 6% concentration		The compounding base alone will be used as a placebo. Each participant will be given each drug and the placebo sequentially in random order. placebo: Compounding base to be used alone as a placebo
All Cause Mortality
	Medications		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Medications		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Medications		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)

Limitations/Caveats

The small number of patients recruited left this study underpowered to uncover significant effects with the medications studied.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.