VulvodyniaNCT05478746
Effects of Flourish HEC on Localized Provoked Vulvodynia
A study testing BioNourish, a component of the Flourish HEC kit in people with Vulvodynia and Vestibulodynia, run by Vaginal Biome Science at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 52 years, women only
- Conditions the study is for
- Vulvodynia, Vestibulodynia, Vulvar Diseases
- What is being tested?
- BioNourish, a component of the Flourish HEC kit
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2022to 15 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 52 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 1. 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
EvoScient Gynecology
Virginia Beach, Virginia, 23455
About this study
Official title: Effects of Flourish HEC Vaginal Care System on Reduction of Pain in Women With Localized Provoked Vulvodynia
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.
Read the detailed description
Vulvodynia is a chronic pain condition affecting the tissues of the external genitalia in women. Localized provoked vulvodynia (LPV) is a specific subset of vulvodynia in which pain occurs upon touching specific sites on the vestibule (or, less commonly, another defined area), and which has been present for more than three months without a known cause. LPV is characterized both by allodynia (pain in response to a normally non-painful stimulus) and hyperalgesia (excessive pain response), leading to pain with sex, tampon use, and even with activities of daily life, such as sitting or wearing tight clothing.
It is becoming accepted that LPV occurs as a type of hypersensitivity to Candida and other antigens which occurs in susceptible women. LPV is an inflammatory condition with increased levels of B-cells, T-cells, and macrophages in tender areas vs. non-tender areas. The inflammatory process sparks neuroproliferation - growth of new nerve endings - which increases the density of nerve fibers in tender spots, especially in areas of lymphoid aggregates.
The vulvar and vaginal microbiomes are connected to each other; species found in one are often found in the other. In fact, Jayaram et al. showed that all vaginal species were also found on the vestibule, and the dominant vaginal species is also the dominant vestibular species, suggesting that vaginal secretions are a major contributor to the vestibular/vulvar microbiome. Three recent studies have examined the link between vulvodynia and the vaginal microbiome. Results vary by study, with one showing differences in the present vaginal microbiomes between women with vulvodynia and healthy women, and others not showing differences. These may be explainable by inclusion/exclusion criteria (two studies excluded women with active yeast infection; one study specified studying generalized, not localized, vulvodynia; while the others did not specify). But it is agreed that past alterations in the microbiome primed women for excessive pain in response to gentle stimuli.
Vaginal microbiome composition is known to affect immune activation in the vagina and vulva. Campisciano and colleagues showed that vaginal dysbiosis is associated with elevated levels of interleukin (IL)-1ra and IL-2, and lower levels of fibroblast growth factor (FGF)-beta and granulocyte-macrophage colony stimulating factor (GM-CSF) than observed in healthy vaginas. Another study by the same group reported associations between vaginal microbiome composition and IL-1alpha and IL-18. Doerflinger showed activation of the innate immune response by Lactobacillus iners (intermediate flora) and Fannyhessea vaginae (associated with bacterial vaginosis), but not L. crispatus (healthy flora). Of greatest relevance, Falsetta and colleagues investigated expression and activation of the toll-like receptor family and found seven of them to be expressed at higher levels in tissue biospies from tender spots in LPV than in control tissue, and that exposure to HIV increased expression of TLR7 expression and the downstream inflammatory molecule IL-6. Notably, no studies have examined whether improving the vaginal microbiome might lead to reductions in immune signaling in vulvodynia.
Taken together, it is reasonable to hypothesize that the constitution of the vaginal microbiome may influence the hypersensitivity to allergens that comprises the cause of LPV. It is also possible that improving the vaginal microbiome may reduce immune cell recruitment and activation, reducing pain. It is predicted that using sequencing-based technology, differences between the vaginal microbiomes of women with LPV and those without will be detectable. Furthermore, its is predicted that using an over-the-counter feminine hygiene system designed to support a healthy vulvovaginal microbiome will reduce pain in women with LPV over and above any reductions observed with standard-of-care treatment.
The investigators recently conducted an 11-week pilot study of similar design. Women with recurrent bacterial vaginosis (BV) were recruited to use the Flourish Vaginal Care System® for 11 weeks. Primary outcomes were vaginal fluid pH and whether or not women had BV recurrence. By the end of the study, the average vaginal fluid pH had fallen from mean (SD) of 4.54 (0.53) at week 0 to 4.08 (0.40) at week 11. At baseline, 30% of women had active BV. (These women were treated with standard of care oral metronidazole). The number of BV-positive women steadily declined until 5 weeks, at which point no woman had BV. There was no recurrence of BV in any woman through the end of the study. Women reported fewer vulvovaginal symptoms throughout the study. An ad hoc follow-up phone survey a year later showed that only one participant had a recurrence of BV since the end of the study. This study shows that the system we propose to use in the present study is able to effect positive changes in the vaginal microbiome.
A follow-up trial at the same center examining the vaginal microbiome using the same system for 6 months has shown very low recurrence rates, based on preliminary analysis, less than 20% in 6 months, compared with other studies showing 3-month recurrence rates of 43% or 62%. This study, which has completed data collection but has not yet been published, also showed that the vaginal microbiome was in a healthy or intermediate community state type (CST; not BV) during use of the system, though it took over 5 weeks of usage for one woman to move from a BV-like CST to a healthy CST. A similar study is underway using the "Flourish HEC" system - a nearly identical kit with a different vaginal moisturizing gel, gentler for those with sensitivities. To date, five participants are enrolled, and only the initial microbiome tests are available. However, study subjects are reporting that they are feeling good while using the system. It is this Flourish HEC system that will be tested in the present study. We emphasize that the vaginal care system is not intended to modify the body; it has no active drug components. Instead, it is a hygiene system that mimics the proper vaginal environment for a healthy microbiome to develop and thrive.
The investigators hypothesize that regular use of the Flourish HEC Vaginal Care System by women with LPV for three months will colonize the vagina and vulva with healthy bacteria, and that this will reduce inflammation, immune system activation, and neuroproliferation, ultimately reducing pain.
- Conditions
- Vulvodynia, Vestibulodynia, Vulvar Diseases, Vulvar Vestibulitis, Vulvar Pain
- Being tested
- BioNourish, a component of the Flourish HEC kit, Control - no intervention
- Keywords
- Localized provoked vulvodynia, Vaginal microbiome, Probiotic, Lactobacillus
- Medical subject headings
- Vulvodynia, Vulvar Diseases, Vulvar Vestibulitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BioNourish, a component of the Flourish HEC kitDevice
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.
Control - no interventionOther
No intervention; participants only receive routine care.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: BioNourish, a component of the Flourish HEC kit |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 2 weeks to 6 weeks to 3 months.
Secondary outcomes (1)
Treatment escalation
A typical vulvodynia patient is started on a mild treatment, then escalated over time if symptoms do not improve. Treatment escalation will be compared between women who use and women who do not use the Flourish HEC system.
Measured: Baseline to 2 weeks to 6 weeks to 3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2022
- Study start26 Sep 2022
- Primary completion15 Jan 2024
- Study completion15 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for VulvodyniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Longitudinal open-label randomized controlled trial. Patients enrolled for 3 months in one of two concurrently enrolling groups.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vaginal Biome Science
- Sponsor type
- University, hospital or other
- Collaborators
- Evvy
- Responsible party
- Sponsor
- Investigators
- Mary Ojo-Carons, MD, Principal investigator, EvoScient Gynecology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05478746
- Sponsor's protocol ID
- LPV0522
- Status last verified
- Feb 2024
- First submitted
- 25 Jul 2022
- Last updated
- 6 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Committee Opinion No 673: Persistent Vulvar Pain. Obstet Gynecol. 2016 Sep;128(3):e78-e84. doi: 10.1097/AOG.0000000000001645.
PubMed 27548558Bornstein 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.
PubMed 27008217Paavonen 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.
PubMed 34222047Liao 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.
PubMed 28062309Tommola 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.
PubMed 27457118Pagan 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.
PubMed 34946169Jayaram 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.
PubMed 24961922Park 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.
PubMed 33652201Mitchell 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.
PubMed 32044865Bedford 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.
PubMed 32135142Campisciano 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.
PubMed 29396486De 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.
PubMed 31736898Doerflinger 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.
PubMed 24403560Falsetta 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.
PubMed 29271858Chidawanyika 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
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Flourish HEC Vaginal Care System on Reduction of Pain in Women With Localized Provoked Vulvodynia
- ClinicalTrials.gov ID
- NCT05478746
- Acronym / sponsor ID
- LPV0522
- Conditions
- Vulvodynia, Vestibulodynia, Vulvar Diseases, Vulvar Vestibulitis, Vulvar Pain
- Keywords
- Localized provoked vulvodynia, Vaginal microbiome, Probiotic, Lactobacillus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Vaginal Biome ScienceUniversity, hospital or other
- Collaborators
- Evvy
- Study start
- 26 Sep 2022 (actual)
- Primary completion
- 15 Jan 2024 (actual)
- Study completion
- 15 Jan 2024 (actual)
- First posted
- 28 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Vulvodynia is a chronic pain condition affecting the tissues of the external genitalia in women. Localized provoked vulvodynia (LPV) is a specific subset of vulvodynia in which pain occurs upon touching specific sites on the vestibule (or, less commonly, another defined area), and which has been present for more than three months without a known cause. LPV is characterized both by allodynia (pain in response to a normally non-painful stimulus) and hyperalgesia (excessive pain response), leading to pain with sex, tampon use, and even with activities of daily life, such as sitting or wearing tight clothing.
It is becoming accepted that LPV occurs as a type of hypersensitivity to Candida and other antigens which occurs in susceptible women. LPV is an inflammatory condition with increased levels of B-cells, T-cells, and macrophages in tender areas vs. non-tender areas. The inflammatory process sparks neuroproliferation - growth of new nerve endings - which increases the density of nerve fibers in tender spots, especially in areas of lymphoid aggregates.
The vulvar and vaginal microbiomes are connected to each other; species found in one are often found in the other. In fact, Jayaram et al. showed that all vaginal species were also found on the vestibule, and the dominant vaginal species is also the dominant vestibular species, suggesting that vaginal secretions are a major contributor to the vestibular/vulvar microbiome. Three recent studies have examined the link between vulvodynia and the vaginal microbiome. Results vary by study, with one showing differences in the present vaginal microbiomes between women with vulvodynia and healthy women, and others not showing differences. These may be explainable by inclusion/exclusion criteria (two studies excluded women with active yeast infection; one study specified studying generalized, not localized, vulvodynia; while the others did not specify). But it is agreed that past alterations in the microbiome primed women for excessive pain in response to gentle stimuli.
Vaginal microbiome composition is known to affect immune activation in the vagina and vulva. Campisciano and colleagues showed that vaginal dysbiosis is associated with elevated levels of interleukin (IL)-1ra and IL-2, and lower levels of fibroblast growth factor (FGF)-beta and granulocyte-macrophage colony stimulating factor (GM-CSF) than observed in healthy vaginas. Another study by the same group reported associations between vaginal microbiome composition and IL-1alpha and IL-18. Doerflinger showed activation of the innate immune response by Lactobacillus iners (intermediate flora) and Fannyhessea vaginae (associated with bacterial vaginosis), but not L. crispatus (healthy flora). Of greatest relevance, Falsetta and colleagues investigated expression and activation of the toll-like receptor family and found seven of them to be expressed at higher levels in tissue biospies from tender spots in LPV than in control tissue, and that exposure to HIV increased expression of TLR7 expression and the downstream inflammatory molecule IL-6. Notably, no studies have examined whether improving the vaginal microbiome might lead to reductions in immune signaling in vulvodynia.
Taken together, it is reasonable to hypothesize that the constitution of the vaginal microbiome may influence the hypersensitivity to allergens that comprises the cause of LPV. It is also possible that improving the vaginal microbiome may reduce immune cell recruitment and activation, reducing pain. It is predicted that using sequencing-based technology, differences between the vaginal microbiomes of women with LPV and those without will be detectable. Furthermore, its is predicted that using an over-the-counter feminine hygiene system designed to support a healthy vulvovaginal microbiome will reduce pain in women with LPV over and above any reductions observed with standard-of-care treatment.
The investigators recently conducted an 11-week pilot study of similar design. Women with recurrent bacterial vaginosis (BV) were recruited to use the Flourish Vaginal Care System® for 11 weeks. Primary outcomes were vaginal fluid pH and whether or not women had BV recurrence. By the end of the study, the average vaginal fluid pH had fallen from mean (SD) of 4.54 (0.53) at week 0 to 4.08 (0.40) at week 11. At baseline, 30% of women had active BV. (These women were treated with standard of care oral metronidazole). The number of BV-positive women steadily declined until 5 weeks, at which point no woman had BV. There was no recurrence of BV in any woman through the end of the study. Women reported fewer vulvovaginal symptoms throughout the study. An ad hoc follow-up phone survey a year later showed that only one participant had a recurrence of BV since the end of the study. This study shows that the system we propose to use in the present study is able to effect positive changes in the vaginal microbiome.
A follow-up trial at the same center examining the vaginal microbiome using the same system for 6 months has shown very low recurrence rates, based on preliminary analysis, less than 20% in 6 months, compared with other studies showing 3-month recurrence rates of 43% or 62%. This study, which has completed data collection but has not yet been published, also showed that the vaginal microbiome was in a healthy or intermediate community state type (CST; not BV) during use of the system, though it took over 5 weeks of usage for one woman to move from a BV-like CST to a healthy CST. A similar study is underway using the "Flourish HEC" system - a nearly identical kit with a different vaginal moisturizing gel, gentler for those with sensitivities. To date, five participants are enrolled, and only the initial microbiome tests are available. However, study subjects are reporting that they are feeling good while using the system. It is this Flourish HEC system that will be tested in the present study. We emphasize that the vaginal care system is not intended to modify the body; it has no active drug components. Instead, it is a hygiene system that mimics the proper vaginal environment for a healthy microbiome to develop and thrive.
The investigators hypothesize that regular use of the Flourish HEC Vaginal Care System by women with LPV for three months will colonize the vagina and vulva with healthy bacteria, and that this will reduce inflammation, immune system activation, and neuroproliferation, ultimately reducing pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Longitudinal open-label randomized controlled trial. Patients enrolled for 3 months in one of two concurrently enrolling groups.
| Arm | Type | Receives |
|---|---|---|
| Routine Care | Other | Other: Control - no interventionParticipants 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. |
| Flourish HEC | Experimental | Device: BioNourish, a component of the Flourish HEC kitParticipants 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. |
Who may qualify
- Ages
- 18 to 52 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 1. 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BioNourish, a component of the Flourish HEC kitBioNourish 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. | Device | Flourish HEC |
| Control - no interventionNo intervention; participants only receive routine care. | Other | Routine Care |
Primary outcome
Vaginal microbiome in women with localized provoked vulvodynia (LPV)
Time frame: Baseline
Using whole-genome sequencing, all microbes present in the vaginal microbiome will be identified and reported for relative abundance.
Changes in the vaginal microbiome in women with localized provoked vulvodynia (LPV) with and without Flourish HEC
Time frame: Baseline to 6 weeks.
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.
Changes in the vaginal microbiome in women with localized provoked vulvodynia (LPV) with and without Flourish HEC
Time frame: Baseline to 3 months.
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.
Changes in the vaginal microbiome in women with localized provoked vulvodynia (LPV) with and without Flourish HEC
Time frame: 6 weeks to 3 months.
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.
Pain intensity by cotton swab test
Time frame: Baseline to 2 weeks to 6 weeks to 3 months.
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.
Vulvovaginal symptoms questionnaire (VSQ) and addendum
Time frame: Baseline to 2 weeks to 6 weeks to 3 months.
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.
1 secondary outcome
Treatment escalation
Time frame: Baseline to 2 weeks to 6 weeks to 3 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
- Background: PubMed 27548558Committee Opinion No 673: Persistent Vulvar Pain. Obstet Gynecol. 2016 Sep;128(3):e78-e84. doi: 10.1097/AOG.0000000000001645.
- Background: PubMed 27008217Bornstein 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.
- Background: PubMed 34222047Paavonen 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.
- Background: PubMed 28062309Liao 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.
- Background: PubMed 27457118Tommola 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.
- Background: PubMed 34946169Pagan 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.
- Background: PubMed 24961922Jayaram 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.
- Background: PubMed 33652201Park 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.
- Background: PubMed 32044865Mitchell 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.
- Background: PubMed 32135142Bedford 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.
- Background: PubMed 29396486Campisciano 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.
- Background: PubMed 31736898De 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.
- Individual participant dataSharing planned: No
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Vulvodynia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary Ojo-Carons, MD principal investigator
EvoScient Gynecology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BioNourish, a component of the Flourish HEC kit in people with Vulvodynia and Vestibulodynia, run by Vaginal Biome Science at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vaginal microbiome in women with localized provoked vulvodynia (LPV) (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05478746, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.