Sexual Penetration Pain in Postmenopausal Women: A Topical Botanical Drug Treatment

• ClinicalTrials.gov Identifier: NCT03682601
• Recruitment Status: Terminated
• First Posted: September 24, 2018
• Last Update Posted: October 8, 2021
• Sponsor: GTO Pharmaceutical, LLC
• Information provided by (Responsible Party): Lila Nachtigall, M.D., Dr. Lila Nachtigall Rapid Medical Research, New York

Study Description

Brief Summary:

This study will evaluate the use of topical 5 or 10% sinecatechins, a botanical drug derived from green tea for the alleviation of sexual pain in the area around the vaginal opening (the vulvar vestibule), that is a main source of pain during sexual contact or dyspareunia, in postmenopausal women, with vulvovaginal atrophy. Women may or may not be using estrogens. Half of the women will receive the study drug, 5 or 10% sinecatechins and half will receive placebo. In addition to the reduction or elimination of pain upon penetration, women may also experience increase in lubrication, arousal and intensity of orgasm

Condition or disease	Intervention/treatment	Phase
Sexual Pain Disorders; Postmenopausal Symptoms; Vulvovaginal Atrophy; Female Sexual Dysfunction; Dyspareunia; Vulvodynia; Vestibulodynia; Arousal Disorders, Sexual; Genito-Pelvic Pain/Penetration Disorder; Female Sexual Arousal Disorder	Drug: 5% sinecatechins ointment; Drug: Placebo; Drug: 10% sinecatechins ointment	Phase 2

Detailed Description:

Topical Veregen (15% sinecatechins) is an FDA approved botanical drug derived from green tea and is approved to be used as multiple doses, three times a day to treat all visible external genital warts.

Topical green tea ointment has been shown to alleviate pain and improve wound healing in the vulvar vestibule for women who have had a recent episiotomy in the medical literature. In private clinical practice, dilute Veregen, sinecatechins ointment, has been effective in alleviating , sexual pain, vulvar vestibular pain, dyspareunia, in postmenopausal women as well as improving overall sexual satisfaction,( increasing lubrication, arousal and quality of orgasm). In this study, dilute Veregen, (5 or 10% sinecatechins) or placebo is being applied, as a single dose, topically, three times/week up to once a day, to alleviate pain in the vulvar vestibule, penetration pain, upon sexual contact or other manipulation of this area in postmenopausal women. Women are eligible whether or not they are currently using any form of estrogen or other hormonal treatments (eg. DHEA). Please note that women not using estrogen or who maybe taking aromatase inhibitors, tamoxifen, SERMS, are also eligible to be included.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, Double Blinded, Placebo Controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double Blinded
• Primary Purpose: Treatment
• Official Title: Sinecatechins Ointment, a Botanical Drug Derived From Green Tea, for the Treatment of Significant to Severe Secondary Provoked Vestibulodynia in Sexually Active, Post-Menopausal Women With Vulvovaginal Atrophy
• Actual Study Start Date: August 30, 2018
• Actual Primary Completion Date: February 12, 2021
• Actual Study Completion Date: February 13, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; 15 postmenopausal women will apply a 1/2 inch strand of Placebo ointment once daily to their vulvar vestibule for a total of 4 weeks. They will come for three office visits with the gynecologist, who will exam their vulvar vestibule and perform a Qtip test. The Qtip test consists of applying pressure with a cotton tipped swab to the vulvar vestibule and asking the participant to rate the degree of pain that they experience on a scale from 0-10 ( 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-9=significant pain; 10=severe pain). A swab will be taken of the lateral vaginal wall for to assess the degree of vaginal atrophy. The participant will fill out questionnaire during office visits with the gynecologist. In addition, questionnaire will be filled out online on a HIPAA compliant web based survey at the end of weeks 1 and 3 and one week after stopping study ointment.	Drug: Placebo; Aquaphor/vehicle; Other Name: Aquafor
Active Comparator: 5% Topical sinecatechins ointment; 15 postmenopausal women will apply a 1/2 inch strand of 5% sinecatechins topical ointment once daily to their vulvar vestibule for a total of 4 weeks. They will come for three office visits with the gynecologist, who will exam their vulvar vestibule and perform a Qtip test. The Qtip test consists of applying pressure with a cotton tipped swab to the vulvar vestibule and asking the participant to rate the degree of pain that they experience on a scale from 0-10 ( 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-9=significant pain; 10=severe pain). A swab will be taken of the lateral vaginal wall for to assess the degree of vaginal atrophy. The participant will fill out questionnaire during office visits with the gynecologist. In addition, questionnaire will be filled out online on a HIPAA compliant web based survey at the end of weeks 1 and 3 and one week after stopping study ointment.	Drug: 5% sinecatechins ointment; Topical 5% sinecatechins ointment will be applied once daily.; Other Name: Veregen ointment
Active Comparator: 10% Topical sinecatechins ointment; 15 postmenopausal women will apply a 1/2 inch strand of 10% sinecatechins topical ointment once daily to their vulvar vestibule for a total of 4 weeks. They will come for three office visits with the gynecologist, who will exam their vulvar vestibule and perform a Qtip test. The Qtip test consists of applying pressure with a cotton tipped swab to the vulvar vestibule and asking the participant to rate the degree of pain that they experience on a scale from 0-10 ( 0=no pain; 1-3=mild pain; 4-6=moderate pain; 7-9=significant pain; 10=severe pain). A swab will be taken of the lateral vaginal wall for to assess the degree of vaginal atrophy. The participant will fill out questionnaire during office visits with the gynecologist. In addition, questionnaire will be filled out online on a HIPAA compliant web based survey at the end of weeks 1 and 3 and one week after stopping study ointment.	Drug: 10% sinecatechins ointment; Topical 10% sinecatechins ointment will be applied three times per week up to once daily.; Other Name: Veregen ointment

Outcome Measures

Primary Outcome Measures :

1. Numerical Rating Scale for pain [ Time Frame: Change in the Numerical Rating Scale for pain will be assessed weekly for 4 weeks including one week after completing use of the study ointment. ]
   Subjects will be asked to rate their pain 0=no pain, 1-3= mild pain, 4-6 =moderate pain; 7-9= significant pain and 10= severe pain

Secondary Outcome Measures :

1. Subjective comments by subject [ Time Frame: To be answered at the end of their participation in the clinical trial. ]

   1. Overall did you benefit from the use of the ointment?

      • None
      • Somewhat
      • Significant

      Please include any comments you would like to share on your experience using the ointment.

      All responses will remain anonymous and strictly confidential.

   2. Did the study ointment decrease your sexual pain?

      • Yes
      • No

      If yes, please specify where:

   3. Did the study ointment increase your positive sexual sensations?

      • Yes
      • No

   4. Did the study ointment increase your level of lubrication in the vaginal and/or vulvar area?

      • Yes
      • No

   5. Have you noticed any increase in your feelings of sexual arousal since you stopped using the study ointment for the past week?

      • Yes
      • No If yes, please explain.
2. Vaginal pH [ Time Frame: To be performed at each office visit , the first office visit; and at the end of the 4th week office visit ]
   A vaginal speculum exam will be performed by the gynecologist to evaluate with a pH paper the vaginal pH
3. Vaginal maturation index [ Time Frame: To be performed twice, once at the first office visit and then at the end of the 4th week office visit ]
   A vaginal speculum exam will be performed by the gynecologist and a gentle swabbing of the lateral vaginal wall will be performed to assess the degree of vaginal atrophy in the postmenopausal subject

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Participant must be a postmenopausal female who has not menstruated for at least one year either because of surgical removal of ovaries and uterus or because of natural menopause. Women taking estrogens, DHEA, can continue to use them during the clinical trial. Women not taking estrogens or are on aromatase inhibitors can enter the trial.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Postmenopausal women

Generally healthy women must meet the following eligibility criteria:

1. For surgically menopausal women, be 20-70 years of age and at least 12 months post menopause.
2. For naturally postmenopausal women, be 40-70 years of age and at least 1 year post menopause (defined as no spontaneous menses for 1 year).
3. Women taking estrogens may enroll in the trial.
4. For women who are not taking any estrogen or who are taking an aromatase inhibitor, In screening their vaginal pH will be 4.6 or greater and their vaginal maturation index will be consistent with vaginal atrophy. Vaginal atrophy is thinning, drying and of the vaginal walls due to having less estrogen in the body.
5. Be, sexually functional, both psychologically and physically, whereby a woman is to be psychologically interested in sexual activity and (unless these activities are precluded by pain) is physically sexually active with regular vestibular including vaginal introital genital manipulation whether through masturbation or partner sex, whether using digits, oral sexual contact, sex toys, and/or penile penetration present at regular intervals each month during the 4-week pre-treatment and the 4- week active treatment period of the study and ending at the 6th- week of their participation in the study.
6. Be able and willing to participate in the study as evidenced by providing written informed consent.

7. Answer affirmatively to ALL of the following questions:

   1. Before your vulvar pain, would you say that in general, your sex life was good and satisfying?
   2. Since you have been experiencing vulvar pain, do you feel you have experienced a meaningful loss in your desire for sex?
   3. Since experiencing vulvar pain, do you feel you have experienced a significant decrease in your sexual activity?
   4. Are you concerned or bothered by your current level of desire for or interest in sex?
   5. Would you like to see an increase in your level of interest or desire for sex and sexual activity?
8. Women can enter the trial if they are taking estrogens.
9. Women can enter the trial if they are taking DHEA.
10. Women can enter the trial if they are not taking estrogens.
11. Women can enter the trial if they are taking aromatase inhibitors.

Exclusion Criteria:

1. Have any physical limitations or sexual trauma that would interfere with normal sexual function.
2. Have used within the last 12 weeks any of the following medications/preparations that may interfere with the study purpose: systemic corticosteroids (acute use for fewer than 7 days is accepted), SSRI's, tricyclic antidepressants, anti-androgens, spironolactone, PDE5 inhibitors (Viagra ®).
3. Be experiencing any chronic or acute life stress relating to any major life change, such as recent loss of income or the death of a close family member, that may, in the opinion of the Investigator, significantly interfere with sexual function.
4. Have significant psychiatric disorder, a significant alcohol or drug dependency and/or be receiving pharmacologic treatment for such illness or disorder.
5. Have evidence of clinically significant organic disorder on the history and/or physical examination that would, in the opinion of the Investigator, put the patient at risk, present the patient from completing the study, or otherwise affect the outcome of the study.
6. Have a history of genital herpes because of the episodic nature of genital herpes and of the known possibility of occurrence of herpetic pain without visible dermatologic manifestations of herpes. Genital herpes and its accompanying genital pain may obscure the source of the genital pain experienced and confound the ability to determine the efficacy of treatment/placebo on endpoint of alleviation of pain in women with secondary provoked vulvar vestibular pain.
7. Have any infection of the genitalia
8. Have lichen sclerosis, lichen planus, contact dermatitis, psoriasis or any inflammatory condition or abrasions of the vulva
9. Have an episiotomy scar in the area where pain is perceived as it may confound the etiology of the perceived pain

10. Have diabetes.

    -

Contacts and Locations

Locations

United States, New York

Lila Nachtigall, M.D.

New York, New York, United States, 10016

Miriam Greene, M.D.

New York, New York, United States, 10016

Cynthia Krause, M.D.

New York, New York, United States, 10128

Janis Enzenbacher, M.D.

Nyack, New York, United States, 10960

Sponsors and Collaborators

GTO Pharmaceutical, LLC

  Study Documents (Full-Text)

Documents provided by Lila Nachtigall, M.D., Dr. Lila Nachtigall Rapid Medical Research, New York:

Study Protocol and Statistical Analysis Plan  [PDF] May 13, 2020

More Information

Publications:

Shahrahmani H, Kariman N, Jannesari S, Rafieian-Kopaei M, Mirzaei M, Ghalandari S, Shahrahmani N, Mardani G. The effect of green tea ointment on episiotomy pain and wound healing in primiparous women: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2018 Mar;32(3):522-530. doi: 10.1002/ptr.5999. Epub 2017 Dec 13.

Goetsch MF, Lim JY, Caughey AB. Locating pain in breast cancer survivors experiencing dyspareunia: a randomized controlled trial. Obstet Gynecol. 2014 Jun;123(6):1231-1236. doi: 10.1097/AOG.0000000000000283.

• Responsible Party: Lila Nachtigall, M.D., Lila Nachtigall, M.D., Professor of Gynecology, Dr. Lila Nachtigall Rapid Medical Research, New York
• ClinicalTrials.gov Identifier: NCT03682601
• Other Study ID Numbers: GTO1
• First Posted: September 24, 2018
• Last Update Posted: October 8, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Lila Nachtigall, M.D., Dr. Lila Nachtigall Rapid Medical Research, New York:

Sexual Pain; Postmenopausal Symptoms; Vulvovaginal Atrophy; Vulvodynia; Dyspareunia; Vestibulodynia; Female Sexual Dysfunction; Arousal Disorders, Sexual; Painful Penetration; Painful intercourse; Vular Pain; Pain at vaginal opening; Entrance Pain; Lack of Lubrication; Lack of Arousal

Additional relevant MeSH terms:

Vulvodynia; Dyspareunia; Vulvar Vestibulitis; Disease; Atrophy; Pelvic Pain; Somatoform Disorders; Sexual Dysfunctions, Psychological; Pathologic Processes; Pathological Conditions, Anatomical; Pain; Neurologic Manifestations; Vulvar Diseases; Sexual Dysfunction, Physiological; Mental Disorders; Vulvitis