Investigation of the Effect of the Female Urinary Microbiome on Incontinence

NCT02835846 | Completed Phase 4 Results

• 1 other identifier: 207777
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This purpose of this study is to understand the types of bacteria that are in the bladder and vagina in patients with overactive bladder (OAB) symptoms and understand if the types of bacteria change when with the use of estrogen in the vagina. The investigators are also trying to understand how estrogen influences the body's ability to make substances called peptides that can kill bacteria.

Conditions

Overactive Bladder; Incontinence; Nocturia

Keywords

Overactive Bladder Syndrome; Female Urinary Microbiome; Urinary Urgency; Estrogen; Nocturia; 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)

Estrogen Arm

EXPERIMENTAL

The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks

Drug: Estrogen Cream

Interventions

Estrogen Cream DRUG

Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.

Also known as: Premarin Cream®

Estrogen Arm

Eligibility Criteria

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

You may qualify if:

• Women who present with symptoms of OAB, defined as a condition characterized by urgency, with or without urgency incontinence, usually with frequency and nocturia in the absence of obvious pathology or infection \[9\], with atrophic vaginitis.
• Postmenopausal by history (i.e., defined as twelve months or greater since last menstrual period), surgical menopause with removal of bilateral ovaries, or age over 55 with a previous hysterectomy (without removal of bilateral ovaries).
• English language skills sufficient to complete questionnaires
• Clinical indication for vaginal estrogen use (i.e., hypoestrogenic findings on physical examination)
• Patients not currently receiving vaginal estrogen therapy

You may not qualify if:

• Patients currently on systemic hormone replacement therapy (HRT) or who have been on HRT within the past three months
• Patients with current diagnosis or history of estrogen dependent malignancies (e.g., breast or endometrial malignancies)
• Contraindication or allergy to estrogen therapy
• Insufficient English language skills to complete study questionnaires
• Women with active, standard culture positive urinary tract infection at baseline assessment, or those with a urine dip positive for leukocytes and nitrates on straight catheterized sample.
• Patients who have received antibiotics within the past two weeks
• Patients with stage 3 or 4 pelvic organ prolapse based on the pelvic organ prolapse quantitation system (POP-q)
• Patients unwilling to use vaginal estrogen preparation
• Patients currently on anticholinergic medications or who have received anticholinergic medications within the past three months
• Patients who have previously failed two medications for treatment of OAB or have previously received more advanced treatment for OAB including intra-vesicle botulinum toxin injections, posterior tibial nerve stimulation, or implantation of a sacral neuromodulator
• Patients wishing to start anticholinergic medication at the initial encounter
• Undiagnosed abnormal genital bleeding
• Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions
• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
• Known liver dysfunction or disease

Sponsors & Collaborators

• Loyola University: lead
• Kimberly-Clark Corporation: collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Related Publications (20)

• 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

• Fouts DE, Pieper R, Szpakowski S, Pohl H, Knoblach S, Suh MJ, Huang ST, Ljungberg I, Sprague BM, Lucas SK, Torralba M, Nelson KE, Groah SL. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J Transl Med. 2012 Aug 28;10:174. doi: 10.1186/1479-5876-10-174.

  PMID: 22929533 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

• Haylen BT, Maher CF, Barber MD, Camargo S, Dandolu V, Digesu A, Goldman HB, Huser M, Milani AL, Moran PA, Schaer GN, Withagen MI. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic organ prolapse (POP). Int Urogynecol J. 2016 Apr;27(4):655-84. doi: 10.1007/s00192-016-3003-y.

  PMID: 26984443 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

• Cardozo LD, Wise BG, Benness CJ. Vaginal oestradiol for the treatment of lower urinary tract symptoms in postmenopausal women--a double-blind placebo-controlled study. J Obstet Gynaecol. 2001 Jul;21(4):383-5. doi: 10.1080/01443610120059941.

  PMID: 12521832 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 KS, Thompson CL, Lai JS, Sexton CC. An overactive bladder symptom and health-related quality of life short-form: validation of the OAB-q SF. Neurourol Urodyn. 2015 Mar;34(3):255-63. doi: 10.1002/nau.22559. Epub 2014 Jan 13.

  PMID: 25783168 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; Nocturia

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

Results Point of Contact

• Title: Alan J Wolfe
• Organization: Loyola University Chicago

awolfe@luc.edu

7082165814

Study Officials

• Alan Wolfe, PhD

  Loyola University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 10, 2016
• First Posted: July 18, 2016
• Study Start: September 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: May 1, 2018
• Last Updated: September 23, 2021
• Results First Posted: September 23, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)