The Estrogen Impact on Overactive Bladder Syndrome: Female Pelvic Floor Microbiomes and Antimicrobial Peptides

NCT02524769 | Completed Results DMC

• 1 other identifier: 207152
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The medical field is beginning to adopt treatments that alter an individual's microbiome to improve patient health; however, this approach has not been adopted for treatment of lower urinary tract symptoms (LUTS). Here, the investigators propose the first step in development of such a therapy. If the investigators hypothesis is correct, the investigators could change the first line of treatment for hypoestrogenic women and develop future therapies that modulate bacteria in the bladder to improve not only LUTS but also treatment response. This could lead to the first treatment for lower urinary disorders that incorporates a person's individual microbiome.

Conditions

Overactive Bladder

Keywords

Urge Urinary Incontinence; Urinary Incontinence

Outcome Measures

Primary Outcomes (1)

• Change in the Relative Abundance of Lactobacillus

  The relative abundance of Lactobacillus to total microbes per sample was measured before and after treatment. The within-participant change in relative abundance of Lactobacillus was calculated subtracting pre-treatment from post-treatment.

  0, 12 weeks

Secondary Outcomes (4)

• Change in OAB Symptoms

  0, 12 weeks

• OAB Symptoms Associated With Relative Abundance of Lactobacillus

  0, 12 weeks

• Change in Urothelial Antimicrobial Peptide (AMP) Levels

  0, 12 weeks

• Change in OAB Symptoms Associated With Change in AMP Levels

  0, 12 weeks

Study Arms (1)

conjugated estrogen

OTHER

All patients in the study will receive 0.625 mg conjugated estrogen/gram to use 0.5 grams twice weekly with the applicator for 12 weeks.

Drug: conjugated estrogen

Interventions

conjugated estrogen DRUG

0.625 mg conjugated estrogen/gram and instructions to use 0.5 grams twice weekly with the applicator.

Also known as: Vaginal estrogen Premarin Cream® 0.625 mg

conjugated estrogen

Eligibility Criteria

• Age: 55 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of Overactive bladder
• Clinical diagnosis of Postmenopausal:
• English language skills sufficient to complete questionnaires
• Clinical indication for vaginal estrogen use
• Not currently receiving vaginal estrogen therapy

You may not qualify if:

• Currently on systemic hormone replacement therapy (HRT) Have been on HRT within the past three months
• Clinical diagnosis of estrogen dependent malignancies
• Allergy to local estrogen therapy
• Insufficient language skills to complete study questionnaires
• Women with active, urinary tract infection
• Received antibiotics within the past two weeks
• Clinical diagnosis of stage 3 or 4 pelvic organ prolapse
• Patient unwilling to use vaginal estrogen preparation
• Currently on anticholinergic medication Have received anticholinergic medication within the past three months
• Previously failed two medications for treatment of OAB Previously received intra-vesicle botulinum toxin injections Previously had posterior tibial nerve stimulation Previously had implantation of sacral neuromodulator
• Patients wishing to start anticholinergic medication at the initial encounter
• Undiagnosed abnormal genital bleeding
• Clinical diagnosis of deep vein thrombosis (DVT) Clinical diagnosis of pulmonary embolism (PE)
• Clinical diagnosis of arterial thromboembolic disease
• Clinical diagnosis of liver dysfunction or disease

Sponsors & Collaborators

• Loyola University: lead

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Related Publications (17)

• Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas-White K, Fok C, Kliethermes S, Schreckenberger PC, Brubaker L, Gai X, Wolfe AJ. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014 Jul 8;5(4):e01283-14. doi: 10.1128/mBio.01283-14.

  PMID: 25006228 BACKGROUND

• Hilt EE, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, Brubaker L, Gai X, Wolfe AJ, Schreckenberger PC. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014 Mar;52(3):871-6. doi: 10.1128/JCM.02876-13. Epub 2013 Dec 26.

  PMID: 24371246 BACKGROUND

• Wolfe AJ, Toh E, Shibata N, Rong R, Kenton K, Fitzgerald M, Mueller ER, Schreckenberger P, Dong Q, Nelson DE, Brubaker L. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012 Apr;50(4):1376-83. doi: 10.1128/JCM.05852-11. Epub 2012 Jan 25.

  PMID: 22278835 BACKGROUND

• Khasriya R, Sathiananthamoorthy S, Ismail S, Kelsey M, Wilson M, Rohn JL, Malone-Lee J. Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol. 2013 Jul;51(7):2054-62. doi: 10.1128/JCM.03314-12. Epub 2013 Apr 17.

  PMID: 23596238 BACKGROUND

• Fok CS, McKinley K, Mueller ER, Kenton K, Schreckenberger P, Wolfe A, Brubaker L. Day of surgery urine cultures identify urogynecologic patients at increased risk for postoperative urinary tract infection. J Urol. 2013 May;189(5):1721-4. doi: 10.1016/j.juro.2012.11.167. Epub 2012 Dec 3.

  PMID: 23219547 BACKGROUND

• Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell DR Jr. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause. 2011 Sep;18(9):962-6. doi: 10.1097/gme.0b013e3182104977.

  PMID: 21532512 BACKGROUND

• Tseng LH, Wang AC, Chang YL, Soong YK, Lloyd LK, Ko YJ. Randomized comparison of tolterodine with vaginal estrogen cream versus tolterodine alone for the treatment of postmenopausal women with overactive bladder syndrome. Neurourol Urodyn. 2009;28(1):47-51. doi: 10.1002/nau.20583.

  PMID: 19089890 BACKGROUND

• Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15.

  PMID: 12811491 BACKGROUND

• Eriksen PS, Rasmussen H. Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol. 1992 Apr 21;44(2):137-44. doi: 10.1016/0028-2243(92)90059-8.

  PMID: 1587379 BACKGROUND

• Brading AF. A myogenic basis for the overactive bladder. Urology. 1997 Dec;50(6A Suppl):57-67; discussion 68-73. doi: 10.1016/s0090-4295(97)00591-8.

  PMID: 9426752 BACKGROUND

• Griebling TL, Liao Z, Smith PG. Systemic and topical hormone therapies reduce vaginal innervation density in postmenopausal women. Menopause. 2012 Jun;19(6):630-5. doi: 10.1097/gme.0b013e31823b8983.

  PMID: 22205148 BACKGROUND

• Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2014 May;21(5):450-8. doi: 10.1097/GME.0b013e3182a4690b.

  PMID: 24080849 BACKGROUND

• Raz R. Urinary tract infection in postmenopausal women. Korean J Urol. 2011 Dec;52(12):801-8. doi: 10.4111/kju.2011.52.12.801. Epub 2011 Dec 20.

  PMID: 22216390 BACKGROUND

• Coyne K, Revicki D, Hunt T, Corey R, Stewart W, Bentkover J, Kurth H, Abrams P. Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: the OAB-q. Qual Life Res. 2002 Sep;11(6):563-74. doi: 10.1023/a:1016370925601.

  PMID: 12206577 BACKGROUND

• 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.

  PMID: 25392183 BACKGROUND

• Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4680-7. doi: 10.1073/pnas.1002611107. Epub 2010 Jun 3.

  PMID: 20534435 BACKGROUND

• Thomas-White K, Taege S, Limeira R, Brincat C, Joyce C, Hilt EE, Mac-Daniel L, Radek KA, Brubaker L, Mueller ER, Wolfe AJ. Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms. Am J Obstet Gynecol. 2020 Nov;223(5):727.e1-727.e11. doi: 10.1016/j.ajog.2020.08.006. Epub 2020 Aug 11.

  PMID: 32791124 DERIVED

MeSH Terms

Conditions

Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urinary Incontinence

Interventions

Estrogens, Conjugated (USP)

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urination Disorders

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Elizabeth Mueller
• Organization: Loyola University Chicago

EMUELLE@lumc.edu

708-216-2180

Study Officials

• Cynthia Brincat, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. PhD

Study Record Dates

• First Submitted: August 7, 2015
• First Posted: August 17, 2015
• Study Start: December 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: June 1, 2017
• Last Updated: April 15, 2021
• Results First Posted: April 15, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)