Effects of Flourish HEC on Localized Provoked Vulvodynia

NCT05478746 | Completed FDA Device

• 1 other identifier: LPV0522
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to determine whether improving the vaginal microbiome in women with localized provoked vulvodynia (LPV) may help improve pain better than routine care alone. The study randomizes women with LPV to either routine care or routine care plus a vaginal hygiene system designed to improve the vaginal microbiome. Women will be assessed for vaginal microbiome, vaginal pH, and pain before enrollment and after 6 weeks, and after 3 months. Women will also have pain assessed 2 weeks after enrollment without assessing vaginal microbiome and pH.

Conditions

Vulvodynia; Vestibulodynia; Vulvar Diseases; Vulvar Vestibulitis; Vulvar Pain

Keywords

Localized provoked vulvodynia; Vaginal microbiome; Probiotic; Lactobacillus

Outcome Measures

Primary Outcomes (6)

• Vaginal microbiome in women with localized provoked vulvodynia (LPV)

  Using whole-genome sequencing, all microbes present in the vaginal microbiome will be identified and reported for relative abundance.

  Baseline

• Changes in the vaginal microbiome in women with localized provoked vulvodynia (LPV) with and without Flourish HEC

  Using whole-genome sequencing, all microbes present in the vaginal microbiome will be identified and reported for relative abundance. Changes in these values from baseline to 6 weeks will be compared in women using or not using the Flourish HEC system.

  Baseline to 6 weeks.

• Changes in the vaginal microbiome in women with localized provoked vulvodynia (LPV) with and without Flourish HEC

  Using whole-genome sequencing, all microbes present in the vaginal microbiome will be identified and reported for relative abundance. Changes in these values from baseline to 3 months will be compared in women using or not using the Flourish HEC system.

  Baseline to 3 months.

• Changes in the vaginal microbiome in women with localized provoked vulvodynia (LPV) with and without Flourish HEC

  Using whole-genome sequencing, all microbes present in the vaginal microbiome will be identified and reported for relative abundance. Changes in these values from 6 weeks to 3 months will be compared in women using or not using the Flourish HEC system.

  6 weeks to 3 months.

• Pain intensity by cotton swab test

  The PI will gently palpate the study participant at selected vulvar and extra-vulvar sites using a cotton swab; the participant will report pain on a scale of 0 (no pain) to 10 (most intense pain imaginable). Changes in pain intensity per location from baseline to 2 weeks, 6 weeks, and 3 months will be compared between women using and not using the Flourish HEC system.

  Baseline to 2 weeks to 6 weeks to 3 months.

• Vulvovaginal symptoms questionnaire (VSQ) and addendum

  Study participants responses to questions on the previously-validated VSQ and not-yet-validated additional questions will be collected on a 4-point Likert scale (0=not at all, 3 = all the time), except when questions are binary by nature. Change in question scores between timepoints will be compared between women who use and women who do not use the Flourish HEC system.

  Baseline to 2 weeks to 6 weeks to 3 months.

Secondary Outcomes (1)

• Treatment escalation

  Baseline to 2 weeks to 6 weeks to 3 months.

Study Arms (2)

Routine Care

OTHER

Participants enrolled in the control arm will undergo routine care for localized provoked vulvodynia according to the doctor's usual recommendations. These may include lidocaine cream, physical therapy, a compounded cream containing a blend of lidocaine, baclofen, amitryptyline, estradiol, testosterone, and bupivacaine, radiofrequency treatment, Naropin or botulinum toxin injections.

Other: Control - no intervention

Flourish HEC

EXPERIMENTAL

Participants in the Flourish HEC arm will undergo routine care as described for the control arm. Instead of lidocaine cream, they will be given a 4% lidocaine gel (called "Relief", to be used up to 4x/day as needed) in an iso-osmotic, pH-balanced gel base. In addition, they will be given 3 products to use as described here, comprising the "Flourish HEC" kit (HEC = hydroxyethylcellulose, the principal gelling compound in the vaginal gel, to distinguish from the original Flourish kit using aloe). 1. "Balance" - external vulvar wash to be used daily in the shower. 2. "BioNourish" - vaginal moisturizing gel to be used every day before bed. Iso-osmotic and pH-adjusted with lactic acid to match healthy vaginal fluid. 3. "BiopHresh" - vaginal homeopathic suppository with 7 vaginal probiotic strains, including Lactobacillus crispatus, to be used every 3rd day before bed.

Device: BioNourish, a component of the Flourish HEC kit

Interventions

BioNourish, a component of the Flourish HEC kit DEVICE

BioNourish is a vaginal moisturizing gel which obtained FDA 510k clearance in 2020. It is one component of the full system being tested. The main intervention is to use this kit to improve the vaginal microbiome.

Flourish HEC

Control - no intervention OTHER

No intervention; participants only receive routine care.

Routine Care

Eligibility Criteria

• Age: 18 Years - 52 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. Premenopausal cis women between ages 18 and 52 diagnosed with LPV via cotton swab test who have experienced symptoms for at least three months, and who do not have another diagnosis which may explain the pain.

You may not qualify if:

• Known allergies or sensitivities to aloe or any other ingredients of the Flourish HEC Vaginal Care System
• Individuals whose pain completely prevents application of intravaginal products (applicators similar in size to a tampon)
• Individuals who are immunosuppressed or otherwise immunocompromised
• Known allergy or sensitivity to metronidazole or fluconazole
• Known active vaginal infection at the beginning of the study
• Anyone who may have mental health disorders or trauma history triggered by answering questions related to vulvar or vaginal health, by pelvic exams, or self-application of vaginal products
• Vulnerable populations: adults unable to consent, individuals who are not yet adults, pregnant or lactating women (or those attempting to become pregnant), and prisoners

Sponsors & Collaborators

• Vaginal Biome Science: lead
• Evvy: collaborator

Study Sites (1)

EvoScient Gynecology

Virginia Beach, Virginia, 23455, United States

Location

Related Publications (17)

• Committee Opinion No 673: Persistent Vulvar Pain. Obstet Gynecol. 2016 Sep;128(3):e78-e84. doi: 10.1097/AOG.0000000000001645.

  PMID: 27548558 BACKGROUND

• Bornstein J, Goldstein AT, Stockdale CK, Bergeron S, Pukall C, Zolnoun D, Coady D; consensus vulvar pain terminology committee of the International Society for the Study of Vulvovaginal Disease (ISSVD), the International Society for the Study of Women's Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS). 2015 ISSVD, ISSWSH and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia. Obstet Gynecol. 2016 Apr;127(4):745-751. doi: 10.1097/AOG.0000000000001359.

  PMID: 27008217 BACKGROUND

• Paavonen J, Eschenbach DA. Localized Provoked Vulvodynia-An Ignored Vulvar Pain Syndrome. Front Cell Infect Microbiol. 2021 Jun 17;11:678961. doi: 10.3389/fcimb.2021.678961. eCollection 2021.

  PMID: 34222047 BACKGROUND

• Liao Z, Chakrabarty A, Mu Y, Bhattacherjee A, Goestch M, Leclair CM, Smith PG. A Local Inflammatory Renin-Angiotensin System Drives Sensory Axon Sprouting in Provoked Vestibulodynia. J Pain. 2017 May;18(5):511-525. doi: 10.1016/j.jpain.2016.12.008. Epub 2017 Jan 3.

  PMID: 28062309 BACKGROUND

• Tommola P, Unkila-Kallio L, Paetau A, Meri S, Kalso E, Paavonen J. Immune activation enhances epithelial nerve growth in provoked vestibulodynia. Am J Obstet Gynecol. 2016 Dec;215(6):768.e1-768.e8. doi: 10.1016/j.ajog.2016.07.037. Epub 2016 Jul 25.

  PMID: 27457118 BACKGROUND

• Pagan L, Ederveen RAM, Huisman BW, Schoones JW, Zwittink RD, Schuren FHJ, Rissmann R, Piek JMJ, van Poelgeest MIE. The Human Vulvar Microbiome: A Systematic Review. Microorganisms. 2021 Dec 12;9(12):2568. doi: 10.3390/microorganisms9122568.

  PMID: 34946169 BACKGROUND

• Jayaram A, Witkin SS, Zhou X, Brown CJ, Rey GE, Linhares IM, Ledger WJ, Forney LJ. The bacterial microbiome in paired vaginal and vestibular samples from women with vulvar vestibulitis syndrome. Pathog Dis. 2014 Dec;72(3):161-6. doi: 10.1111/2049-632X.12197. Epub 2014 Jul 10.

  PMID: 24961922 BACKGROUND

• Park SY, Lee ES, Lee SR, Kim SH, Chae HD. Vaginal Microbiome Is Associated With Vulvodynia, Vulvar Pain Syndrome: A Case-Control Study. Sex Med. 2021 Apr;9(2):100314. doi: 10.1016/j.esxm.2020.100314. Epub 2021 Feb 27.

  PMID: 33652201 BACKGROUND

• Mitchell CM, Watson L, Mitchell AJ, Hyrien O, Bergerat A, Valint DJ, Pascale A, Hoffman N, Srinivasan S, Fredricks DN. Vaginal Microbiota and Mucosal Immune Markers in Women With Vulvovaginal Discomfort. Sex Transm Dis. 2020 Apr;47(4):269-274. doi: 10.1097/OLQ.0000000000001143.

  PMID: 32044865 BACKGROUND

• Bedford L, Parker SE, Davis E, Salzman E, Hillier SL, Foxman B, Harlow BL. Characteristics of the vaginal microbiome in women with and without clinically confirmed vulvodynia. Am J Obstet Gynecol. 2020 Sep;223(3):406.e1-406.e16. doi: 10.1016/j.ajog.2020.02.039. Epub 2020 Mar 2.

  PMID: 32135142 BACKGROUND

• Campisciano G, Zanotta N, Licastro D, De Seta F, Comar M. In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis. Sci Rep. 2018 Feb 2;8(1):2307. doi: 10.1038/s41598-018-20649-x.

  PMID: 29396486 BACKGROUND

• De Seta F, Campisciano G, Zanotta N, Ricci G, Comar M. The Vaginal Community State Types Microbiome-Immune Network as Key Factor for Bacterial Vaginosis and Aerobic Vaginitis. Front Microbiol. 2019 Oct 30;10:2451. doi: 10.3389/fmicb.2019.02451. eCollection 2019.

  PMID: 31736898 BACKGROUND

• Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis. 2014 Jun 15;209(12):1989-99. doi: 10.1093/infdis/jiu004. Epub 2014 Jan 7.

  PMID: 24403560 BACKGROUND

• Falsetta ML, Foster DC, Woeller CF, Pollock SJ, Bonham AD, Piekna-Przybylska D, Maggirwar SB, Haidaris CG, Phipps RP. Toll-Like Receptor Signaling Contributes to Proinflammatory Mediator Production in Localized Provoked Vulvodynia. J Low Genit Tract Dis. 2018 Jan;22(1):52-57. doi: 10.1097/LGT.0000000000000364.

  PMID: 29271858 BACKGROUND

• Chidawanyika T, Yi CHC, Kelly-Martin R, Cleland J, DuPriest E. Clinical trial to survey results of Flourish vaginal care system for recurrent BV [A80]. Obstet Gynecol. 2022;139:24S. doi:10.1097/01.AOG.0000826648.49549.01

  BACKGROUND

• Bradshaw CS, Morton AN, Hocking J, Garland SM, Morris MB, Moss LM, Horvath LB, Kuzevska I, Fairley CK. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006 Jun 1;193(11):1478-86. doi: 10.1086/503780. Epub 2006 Apr 26.

  PMID: 16652274 BACKGROUND

• Sobel JD, Schmitt C, Meriwether C. Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J Infect Dis. 1993 Mar;167(3):783-4. doi: 10.1093/infdis/167.3.783. No abstract available.

  PMID: 8440952 BACKGROUND

MeSH Terms

Conditions

Vulvodynia; Vulvar Diseases; Vulvar Vestibulitis

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vulvitis

Study Officials

• Mary Ojo-Carons, MD

  EvoScient Gynecology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Longitudinal open-label randomized controlled trial. Patients enrolled for 3 months in one of two concurrently enrolling groups.

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: July 28, 2022
• Study Start: September 26, 2022
• Primary Completion: January 15, 2024
• Study Completion: January 15, 2024
• Last Updated: February 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)