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

NCT03682601 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GTO1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

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

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

Outcome Measures

Primary Outcomes (1)

• Numerical Rating Scale for Pain

  Scale Title: Numerical Pain Scale to measure overall pain perceived from vulvar vestibule. Minimum value of scale: 0; Maximum value of scale: 10. Subjects were asked to rate from 0 to 10 pain perceived from their vulvar vestibule. The mean (standard error) for Numerical Pain Scale at each visit was calculated. A higher Numerical Rating Score means worse outcome and lower Numerical Rating Score means a better outcome. The following Numerical Rating Scale categories for Pain definition were utilized: 0=no pain, 1-3=mild pain, 4-6=moderate pain; 7-9=significant pain and 10=severe pain.

  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 (1)

• Q-tip Test Test for Pain on the Vulvar Vestibule

  Q-tip test score for pain was assessed at Visit 1 (initial visit); Visit 2 (at 2 weeks), and Visit 3 (at 4 weeks).

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

5% Topical sinecatechins ointment

ACTIVE COMPARATOR

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

10% Topical sinecatechins ointment

ACTIVE COMPARATOR

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

Interventions

5% sinecatechins ointment DRUG

Topical 5% sinecatechins ointment will be applied once daily.

Also known as: Veregen ointment

5% Topical sinecatechins ointment

Placebo DRUG

Aquaphor/vehicle

Also known as: Aquaphor

Placebo

10% sinecatechins ointment DRUG

Topical 10% sinecatechins ointment will be applied three times per week up to once daily.

Also known as: Veregen ointment

10% Topical sinecatechins ointment

Eligibility Criteria

• Age: 20 Years - 70 Years
• Gender Eligibility Details: 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.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Generally healthy women must meet the following eligibility criteria:
• For surgically menopausal women, be 20-70 years of age and at least 12 months post menopause.
• 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).
• Women taking estrogens may enroll in the trial.
• 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.
• 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.
• Be able and willing to participate in the study as evidenced by providing written informed consent.
• Answer affirmatively to all of the following questions:
• Before your vulvar pain, would you say that in general, your sex life was good and satisfying?
• Since you have been experiencing vulvar pain, do you feel you have experienced a meaningful loss in your desire for sex?
• Since experiencing vulvar pain, do you feel you have experienced a significant decrease in your sexual activity?
• Are you concerned or bothered by your current level of desire for or interest in sex?
• Would you like to see an increase in your level of interest or desire for sex and sexual activity?
• Women can enter the trial if they are taking estrogens.
• Women can enter the trial if they are taking DHEA.

You may not qualify if:

• Have any physical limitations or sexual trauma that would interfere with normal sexual function.
• 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 ®).
• 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.
• Have significant psychiatric disorder, a significant alcohol or drug dependency and/or be receiving pharmacologic treatment for such illness or disorder.
• 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.
• 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.
• Have any infection of the genitalia
• Have lichen sclerosis, lichen planus, contact dermatitis, psoriasis or any inflammatory condition or abrasions of the vulva
• Have an episiotomy scar in the area where pain is perceived as it may confound the etiology of the perceived pain
• Have diabetes.

Sponsors & Collaborators

• GTO Pharmaceutical, LLC: lead

Study Sites (4)

Lila Nachtigall, M.D.

New York, New York, 10016, United States

Location

Miriam Greene, M.D.

New York, New York, 10016, United States

Location

Cynthia Krause, M.D.

New York, New York, 10128, United States

Location

Janis Enzenbacher, M.D.

Nyack, New York, 10960, United States

Location

Related Publications (2)

• 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.

  PMID: 29235159 BACKGROUND

• 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.

  PMID: 24807329 BACKGROUND

MeSH Terms

Conditions

Dyspareunia; Vulvodynia; Sexual Dysfunctions, Psychological

Interventions

polyphenon E; Petrolatum

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Mental Disorders; Vulvar Diseases

Intervention Hierarchy (Ancestors)

Hydrocarbons; Organic Chemicals

Limitations and Caveats

Early termination due to Coronavirus disease (COVID-19) pandemic.

Results Point of Contact

• Title: Clinical Trial Coordinator
• Organization: GTO Pharma

akhmea01@gmail.com

9175436934

Study Officials

• Lila Nachtigall, M.D.

  Rapid Medical Research, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lila Nachtigall, M.D., Professor of Gynecology

Model Details: Randomized, Double Blinded, Placebo Controlled

Study Record Dates

• First Submitted: September 14, 2018
• First Posted: September 24, 2018
• Study Start: August 30, 2018
• Primary Completion: February 12, 2021
• Study Completion: February 13, 2021
• Last Updated: July 27, 2022
• Results First Posted: June 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)