Clinical trial NCT03682601: Sexual Penetration Pain in Postmenopausal Women: A Topical Botanical Drug 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Keywords: Sexual Pain
Postmenopausal Symptoms
Vulvovaginal Atrophy
Vulvodynia
Dyspareunia
Vestibulodynia
Female Sexual Dysfunction
Arousal Disorders, Sexual
Painful Penetration
Painful intercourse
Vulvar Pain
Pain at vaginal opening
Entrance Pain
Lack of Lubrication
Lack of Arousal
Lead sponsor: GTO Pharmaceutical, LLC
Sponsor class: OTHER
First posted: 2018-09-24
Enrollment: 32
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double Blinded, Placebo Controlled
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

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 power of hydrogen (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, phosphodiesterase type 5 (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.

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Primary outcomes:
measure: Numerical Rating Scale for Pain
timeFrame: Numerical Rating Scale for pain was assessed at Visit 1 (initial visit); Visit 2 (at 2 weeks), and Visit 3 (at 4 weeks).
Secondary outcomes:
measure: Q-tip Test Test for Pain on the Vulvar Vestibule
timeFrame: Q-tip test score for pain was assessed at Visit 1 (initial visit); Visit 2 (at 2 weeks), and Visit 3 (at 4 weeks).
Other outcomes:
Locations:
city: New York
country: United States
facility: Lila Nachtigall, M.D.
state: New York
city: New York
country: United States
facility: Miriam Greene, M.D.
state: New York
city: New York
country: United States
facility: Cynthia Krause, M.D.
state: New York
city: Nyack
country: United States
facility: Janis Enzenbacher, M.D.
state: New York
Study officials:
affiliation: Rapid Medical Research, New York
name: Lila Nachtigall, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.