Vaginal and Urinary Microbiome Trial
Primary Purpose
Atrophic Vaginitis, Menopause, Recurrent Urinary Tract Infections
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Conjugated equine estrogen topical cream
Apricot kernel oil
Sponsored by
About this trial
This is an interventional basic science trial for Atrophic Vaginitis focused on measuring Postmenopausal
Eligibility Criteria
Inclusion Criteria:
- Age 18-years old
- Women who qualify for vaginal estrogen
- Suitability for follow-up
- Hormonally post-menopausal status: Bilateral past ovarian removal, ≥1 year since last menses if uterus in place, OR hysterectomized woman with ≥1 ovary in place AND >1 year of menopausal symptoms or laboratory confirmation of menopausal hormonal status (such as serum follicle stimulation hormone >25 IU/mL)
- GSM symptoms (including, but not limited to genital symptoms of dryness, burning, itching, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired sexual function; and urinary symptoms of urgency, frequency, dysuria and recurrent (UTIs)
Exclusion Criteria:
- Age < 18-years old
- Known allergic reaction or other adverse reactions to Premarin® or any of its components or apricot kernel oil
- Nut allergy
- Inability to use or place vaginal therapy due to altered mental status or anatomical reasons
- Already using vaginal estrogen or apricot kernel oil in the past two weeks
- Known active vaginal infection (symptomatic and/or untreated) or completion of treatment for bacterial vaginosis or cervical/vaginal infection within one week of recruitment
- History of recurrent or chronic bacterial vaginosis with > 2 episodes per year or symptoms reported for > 6 months out of the last year.
- History of active vaginal ulcerative disease (active ulcers from atrophy, herpes symptoms at recruitment or herpes with >2 outbreaks per year or last outbreak <1month ago, or vaginal laceration.
- Chronic antibiotic or probiotic use for indications not listed.
- Pelvic organ prolapse beyond the hymenal ring
- Using a vaginal pessary or indwelling urinary catheter
- Evidence of active urinary tract infection by history and symptoms, urine dipstick, or urine culture on day of presentation or within last 2 weeks (defined as ≥ 100,000 colonies same pathologic bacteria on clean catch or 10,000 colonies on straight catheter specimen)
- Recurrent urinary tract infection 3 episodes with the last year or 2 episodes within the last 6 months.
- History of venous or arterial thromboembolism or genetic predisposition to thromboembolism.
- Ovarian cancer and estrogen responsive cancer including endometrial or breast or breast cancer history of unknown hormonal status
- Vaginal mesh erosion, sutures visible in the vagina or granulation tissue
- Uncorrected vesicovaginal or rectovaginal fistula
- Severe fecal or anal incontinence
- Active vulvar dermatoses (lichen sclerosis, Behcet's disease, vulvar eczema) and on chronic topical steroids.
- Subjects with absolute contraindications to estrogen, such as diabetes mellitus with end-organ damage and vascular disease, impaired liver function or a hepatic hemangioma, chronic renal disease, migraine with aura, systemic lupus erythematosus with prior thrombosis or vascular damage or other end-organ damage
- Patients < 6 weeks postop
- Inability to speak or read English
Sites / Locations
- Health Care Outpatient Center and Springs Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Conjugated equine estrogen topical cream
Apricot kernel oil
Arm Description
The conjugated equine estrogen topical vaginal cream 0.5 grams per vagina two times per week at nights for 3 months.
One teaspoonful per vagina every night for 3 months.
Outcomes
Primary Outcome Measures
Vaginal and urinary predominance of anaerobic/fastidious taxonomy of micro-organisms on genomic, microbial DNA analysis of vaginal and urinary specimens.
Predominance (greater than 50%) in vaginal and urinary specimen of anaerobic and/or fastidious organisms in the study population compared between conjugated equine estrogen cream (Premarin) and apricot kernel oil. The primary analysis will compare the prevalence of genomic taxonomic anaerobic and/or fastidious organism predominance (>50%) between the estrogen group and the non-estrogen alternative group.
Secondary Outcome Measures
Change in vaginal symptom questionnaire (VSQ)
Change in vaginal symptoms as assessed by vulvovaginal symptom questionnaire (VSQ) at baseline and after treatment.
Vaginal and urinary predominance of anaerobic/fastidious taxonomy of micro-organisms on genomic, microbial DNA analysis of vaginal and urinary specimens.
Predominance (greater than 50%) in vaginal and urinary specimen of anaerobic and/or fastidious organisms in the study population compared between the conjugated equine estrogen cream (Premarin) and apricot kernel oil. The primary analysis will compare the prevalence of genomic taxonomic anaerobic and/or fastidious organism predominance (>50%) between the baseline patients and the patients at 3 months and compare the change in prevalence in this taxonomic predominance between the two study groups.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02869165
Brief Title
Vaginal and Urinary Microbiome Trial
Official Title
The Effects of Vaginal Estrogen and a Nonhormonal Alternative on the Vaginal and Urinary Microbiome in Women With Genitourinary Syndrome of Menopause: A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 2017 (Actual)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
December 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Louisville
4. Oversight
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.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A randomized controlled trial looking at the effects of vaginal estrogen and a nonhormonal alternative on the vaginal and urinary microbiome in women with genitourinary syndrome of menopause.
Detailed Description
This is a study is looking at the effects of vaginal estrogen and a nonhormonal alternative on the vaginal and urinary microbiome in women with genitourinary syndrome of menopause. The primary objective is to describe the bacterial communities associated in the vagina and urine of postmenopausal women receiving treatment for genitourinary syndrome of menopause with conjugated equine estrogen topical cream (Premarin®) and a nonhormonal alternative (apricot kernel oil). The participants will be randomized to either conjugated equine estrogen topical vaginal cream or apricot kernel oil. They will be given validated questionnaires to assess their urinary and vaginal symptoms, sexual function, quality of life, and impressions of severity and improvement.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrophic Vaginitis, Menopause, Recurrent Urinary Tract Infections
Keywords
Postmenopausal
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Conjugated equine estrogen topical cream
Arm Type
Experimental
Arm Description
The conjugated equine estrogen topical vaginal cream 0.5 grams per vagina two times per week at nights for 3 months.
Arm Title
Apricot kernel oil
Arm Type
Experimental
Arm Description
One teaspoonful per vagina every night for 3 months.
Intervention Type
Drug
Intervention Name(s)
Conjugated equine estrogen topical cream
Other Intervention Name(s)
Premarin vaginal cream, Vaginal estrogen cream, CEE topical cream
Intervention Description
Comparison of the bacterial communities in the vagina and urine of postmenopausal women who use Premarin vaginal cream versus apricot kernel oil and to themselves before and after use.
Intervention Type
Drug
Intervention Name(s)
Apricot kernel oil
Other Intervention Name(s)
Natural oil, Organic oil
Intervention Description
Comparison of the bacterial communities in the vagina and urine of postmenopausal women who use Premarin vaginal cream versus apricot kernel oil and to themselves before and after use.
Primary Outcome Measure Information:
Title
Vaginal and urinary predominance of anaerobic/fastidious taxonomy of micro-organisms on genomic, microbial DNA analysis of vaginal and urinary specimens.
Description
Predominance (greater than 50%) in vaginal and urinary specimen of anaerobic and/or fastidious organisms in the study population compared between conjugated equine estrogen cream (Premarin) and apricot kernel oil. The primary analysis will compare the prevalence of genomic taxonomic anaerobic and/or fastidious organism predominance (>50%) between the estrogen group and the non-estrogen alternative group.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change in vaginal symptom questionnaire (VSQ)
Description
Change in vaginal symptoms as assessed by vulvovaginal symptom questionnaire (VSQ) at baseline and after treatment.
Time Frame
3 months
Title
Vaginal and urinary predominance of anaerobic/fastidious taxonomy of micro-organisms on genomic, microbial DNA analysis of vaginal and urinary specimens.
Description
Predominance (greater than 50%) in vaginal and urinary specimen of anaerobic and/or fastidious organisms in the study population compared between the conjugated equine estrogen cream (Premarin) and apricot kernel oil. The primary analysis will compare the prevalence of genomic taxonomic anaerobic and/or fastidious organism predominance (>50%) between the baseline patients and the patients at 3 months and compare the change in prevalence in this taxonomic predominance between the two study groups.
Time Frame
3 months
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Must be genetically female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age 18-years old
Women who qualify for vaginal estrogen
Suitability for follow-up
Hormonally post-menopausal status: Bilateral past ovarian removal, ≥1 year since last menses if uterus in place, OR hysterectomized woman with ≥1 ovary in place AND >1 year of menopausal symptoms or laboratory confirmation of menopausal hormonal status (such as serum follicle stimulation hormone >25 IU/mL)
GSM symptoms (including, but not limited to genital symptoms of dryness, burning, itching, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired sexual function; and urinary symptoms of urgency, frequency, dysuria and recurrent (UTIs)
Exclusion Criteria:
Age < 18-years old
Known allergic reaction or other adverse reactions to Premarin® or any of its components or apricot kernel oil
Nut allergy
Inability to use or place vaginal therapy due to altered mental status or anatomical reasons
Already using vaginal estrogen or apricot kernel oil in the past two weeks
Known active vaginal infection (symptomatic and/or untreated) or completion of treatment for bacterial vaginosis or cervical/vaginal infection within one week of recruitment
History of recurrent or chronic bacterial vaginosis with > 2 episodes per year or symptoms reported for > 6 months out of the last year.
History of active vaginal ulcerative disease (active ulcers from atrophy, herpes symptoms at recruitment or herpes with >2 outbreaks per year or last outbreak <1month ago, or vaginal laceration.
Chronic antibiotic or probiotic use for indications not listed.
Pelvic organ prolapse beyond the hymenal ring
Using a vaginal pessary or indwelling urinary catheter
Evidence of active urinary tract infection by history and symptoms, urine dipstick, or urine culture on day of presentation or within last 2 weeks (defined as ≥ 100,000 colonies same pathologic bacteria on clean catch or 10,000 colonies on straight catheter specimen)
Recurrent urinary tract infection 3 episodes with the last year or 2 episodes within the last 6 months.
History of venous or arterial thromboembolism or genetic predisposition to thromboembolism.
Ovarian cancer and estrogen responsive cancer including endometrial or breast or breast cancer history of unknown hormonal status
Vaginal mesh erosion, sutures visible in the vagina or granulation tissue
Uncorrected vesicovaginal or rectovaginal fistula
Severe fecal or anal incontinence
Active vulvar dermatoses (lichen sclerosis, Behcet's disease, vulvar eczema) and on chronic topical steroids.
Subjects with absolute contraindications to estrogen, such as diabetes mellitus with end-organ damage and vascular disease, impaired liver function or a hepatic hemangioma, chronic renal disease, migraine with aura, systemic lupus erythematosus with prior thrombosis or vascular damage or other end-organ damage
Patients < 6 weeks postop
Inability to speak or read English
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deslyn Hobson, M.D.
Organizational Affiliation
University of Louisville School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Health Care Outpatient Center and Springs Medical Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202 and 40205
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23985562
Citation
Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013 Sep;20(9):888-902; quiz 903-4. doi: 10.1097/GME.0b013e3182a122c2.
Results Reference
result
PubMed Identifier
23935388
Citation
Parish SJ, Nappi RE, Krychman ML, Kellogg-Spadt S, Simon JA, Goldstein JA, Kingsberg SA. Impact of vulvovaginal health on postmenopausal women: a review of surveys on symptoms of vulvovaginal atrophy. Int J Womens Health. 2013 Jul 29;5:437-47. doi: 10.2147/IJWH.S44579. Print 2013.
Results Reference
result
PubMed Identifier
16458626
Citation
Danforth KN, Townsend MK, Lifford K, Curhan GC, Resnick NM, Grodstein F. Risk factors for urinary incontinence among middle-aged women. Am J Obstet Gynecol. 2006 Feb;194(2):339-45. doi: 10.1016/j.ajog.2005.07.051.
Results Reference
result
PubMed Identifier
8293835
Citation
Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril. 1994 Jan;61(1):178-80. doi: 10.1016/s0015-0282(16)56474-7.
Results Reference
result
PubMed Identifier
22047020
Citation
Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011 Nov 2;11:244. doi: 10.1186/1471-2180-11-244.
Results Reference
result
PubMed Identifier
17054136
Citation
Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001500. doi: 10.1002/14651858.CD001500.pub2.
Results Reference
result
PubMed Identifier
21251190
Citation
Lamont RF, Sobel JD, Akins RA, Hassan SS, Chaiworapongsa T, Kusanovic JP, Romero R. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG. 2011 Apr;118(5):533-49. doi: 10.1111/j.1471-0528.2010.02840.x. Epub 2011 Jan 20.
Results Reference
result
PubMed Identifier
22073175
Citation
Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, Koenig D, Gloor GB, Reid G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One. 2011;6(11):e26602. doi: 10.1371/journal.pone.0026602. Epub 2011 Nov 2.
Results Reference
result
PubMed Identifier
22143133
Citation
Martin DH. The microbiota of the vagina and its influence on women's health and disease. Am J Med Sci. 2012 Jan;343(1):2-9. doi: 10.1097/MAJ.0b013e31823ea228.
Results Reference
result
PubMed Identifier
8794418
Citation
Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996 Apr;23(3):259-63. doi: 10.1016/0378-5122(95)00955-8.
Results Reference
result
PubMed Identifier
18489500
Citation
Coyne KS, Margolis MK, Thompson C, Kopp Z. Psychometric equivalence of the OAB-q in Danish, German, Polish, Swedish, and Turkish. Value Health. 2008 Dec;11(7):1096-101. doi: 10.1111/j.1524-4733.2008.00346.x. Epub 2008 May 16.
Results Reference
result
PubMed Identifier
23632798
Citation
Rogers RG, Rockwood TH, Constantine ML, Thakar R, Kammerer-Doak DN, Pauls RN, Parekh M, Ridgeway B, Jha S, Pitkin J, Reid F, Sutherland SE, Lukacz ES, Domoney C, Sand P, Davila GW, Espuna Pons ME. A new measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Int Urogynecol J. 2013 Jul;24(7):1091-103. doi: 10.1007/s00192-012-2020-8. Epub 2013 Apr 30.
Results Reference
result
PubMed Identifier
11166145
Citation
Hopwood P, Fletcher I, Lee A, Al Ghazal S. A body image scale for use with cancer patients. Eur J Cancer. 2001 Jan;37(2):189-97. doi: 10.1016/s0959-8049(00)00353-1.
Results Reference
result
PubMed Identifier
16647928
Citation
Jelovsek JE, Barber MD. Women seeking treatment for advanced pelvic organ prolapse have decreased body image and quality of life. Am J Obstet Gynecol. 2006 May;194(5):1455-61. doi: 10.1016/j.ajog.2006.01.060.
Results Reference
result
PubMed Identifier
8628042
Citation
Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003.
Results Reference
result
PubMed Identifier
12861145
Citation
Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol. 2003 Jul;189(1):98-101. doi: 10.1067/mob.2003.379.
Results Reference
result
PubMed Identifier
19252451
Citation
Freedman M, Kaunitz AM, Reape KZ, Hait H, Shu H. Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy. Menopause. 2009 Jul-Aug;16(4):735-41. doi: 10.1097/gme.0b013e318199e734.
Results Reference
result
PubMed Identifier
18698279
Citation
Levine KB, Williams RE, Hartmann KE. Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women. Menopause. 2008 Jul-Aug;15(4 Pt 1):661-6. doi: 10.1097/gme.0b013e31815a5168.
Results Reference
result
PubMed Identifier
25415166
Citation
Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526.
Results Reference
result
PubMed Identifier
25392183
Citation
Rahn DD, Ward RM, Sanses TV, Carberry C, Mamik MM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines. Int Urogynecol J. 2015 Jan;26(1):3-13. doi: 10.1007/s00192-014-2554-z. Epub 2014 Nov 13.
Results Reference
result
PubMed Identifier
23481118
Citation
Erekson EA, Yip SO, Wedderburn TS, Martin DK, Li FY, Choi JN, Kenton KS, Fried TR. The Vulvovaginal Symptoms Questionnaire: a questionnaire for measuring vulvovaginal symptoms in postmenopausal women. Menopause. 2013 Sep;20(9):973-9. doi: 10.1097/GME.0b013e318282600b.
Results Reference
result
Links:
URL
https://www.oecd.org/els/health-systems/Health-at-a-Glance-2013.pdf
Description
Organization for Economic Cooperation and Development. Health at a glance 2013: OECD indicators.
Learn more about this trial
Vaginal and Urinary Microbiome Trial
We'll reach out to this number within 24 hrs