Bacterial Genomic Sequencing in Overactive Bladder

NCT01642277 | Completed Phase 2 Results

• 1 other identifier: 204195
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

No one really knows what causes overactive bladder syndrome (OAB). Urinary tract infection (UTI)causes similar symptoms to OAB with the difference being the presence of bacteria, as evidenced by routine microbiology cultures. Recent work by the group on the genitourinary microbiome (GUM) has shown that female urine, even in the absence of culture evidence of bacteria does have evidence of bacterial DNA. Bacterial 16S rRNA can be isolated from urine and sequenced to identify bacterial species present in urine. From this the investigators can hypothesize that urinary bacteria contribute to urinary symptoms and that there is a difference in the bacterial communities in the urine of women who respond to Solifenacin, a drug used to treat OAB, versus those that do not.

Conditions

Overactive Bladder

Keywords

Overactive Bladder; OAB; Urinary Tract Infection; UTI; Microbiome; Bacteria; Solifenacin; 16S rRNA sequence

Outcome Measures

Primary Outcomes (1)

• Bacterial Genomic Sequencing

  Participants were classified into Low Biomass, Lactobacillus, Gardnerella, Diverse, and Other urotypes based on the bacterial DNA at baseline.

  12 weeks

Secondary Outcomes (2)

• Assessment of Overactive Bladder Questionnaire (OABQ)

  End of study (Week 12)

• Assessment of Pelvic Floor Disease Inventory (PFDI) Questionnaire

  12 weeks

Study Arms (2)

Women using Solifenacin for OAB treatment

EXPERIMENTAL

Solifenacin treated women: Women with OAB who are prescribed solifenacin

Drug: Solifenacin

Control: Women without OAB

NO INTERVENTION

Women without OAB who are not prescribed solifenacin.

Interventions

Solifenacin DRUG

5 mg for 4 weeks with option to increase to 10 mg for an additional 8 weeks

Also known as: Vesicare

Women using Solifenacin for OAB treatment

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Controls: Women without bother from urinary symptoms will be screened for potential study participation using the pelvic floor distress inventory (PFDI). Women with negative urinary responses will be further screened for participation using the following eligibility criteria:
• no anticholinergic medications for bladder conditions,
• no antibiotic exposure in the past 4 weeks for any reason,
• no immunologic deficiency,
• no pelvic malignancy or pelvic radiation, and
• Untreated symptomatic POP \> POP-Q Stage II.
• OAB cohort: Women with bother from overactive bladder symptoms will be screened for potential study participation using the pelvic floor distress inventory (PFDI). Women with positive urinary responses for urge predominant symptoms will be further screened for participation using the following eligibility criteria:
• willing to take Solifenacin as treatment for OAB,
• no neurological disease known to affect the lower urinary tract,
• no current UTI (based on urine dipstick) or recurrent UTI,
• no antibiotic exposure in the past 4 weeks for any reason,
• no immunologic deficiency,
• no pelvic malignancy or pelvic radiation,
• untreated symptomatic POP \> POP-Q Stage II,
• no contraindications to receiving Solifenacin.

You may not qualify if:

• Women who are of child-bearing potential who are pregnant, nursing, intending to become pregnant during the study or not practicing a reliable form of contraception are also excluded.

Sponsors & Collaborators

• Loyola University: lead
• Astellas Pharma US, Inc.: collaborator

Study Sites (1)

Loyola University Chicago Health Sciences Division

Maywood, Illinois, 60153, United States

Location

Related Publications (17)

• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. doi: 10.1002/nau.20798.

  PMID: 19941278 BACKGROUND

• Hartmann KE, McPheeters ML, Biller DH, Ward RM, McKoy JN, Jerome RN, Micucci SR, Meints L, Fisher JA, Scott TA, Slaughter JC, Blume JD. Treatment of overactive bladder in women. Evid Rep Technol Assess (Full Rep). 2009 Aug;(187):1-120, v.

  PMID: 19947666 BACKGROUND

• Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int. 2011 Oct;108(7):1132-8. doi: 10.1111/j.1464-410X.2010.09993.x. Epub 2011 Jan 13.

  PMID: 21231991 BACKGROUND

• de Boer TA, Salvatore S, Cardozo L, Chapple C, Kelleher C, van Kerrebroeck P, Kirby MG, Koelbl H, Espuna-Pons M, Milsom I, Tubaro A, Wagg A, Vierhout ME. Pelvic organ prolapse and overactive bladder. Neurourol Urodyn. 2010;29(1):30-9. doi: 10.1002/nau.20858.

  PMID: 20025017 BACKGROUND

• Sajadi KP, Vasavada SP. Overactive bladder after sling surgery. Curr Urol Rep. 2010 Nov;11(6):366-71. doi: 10.1007/s11934-010-0136-2.

  PMID: 20803179 BACKGROUND

• Mostwin JL. Pathophysiology: the varieties of bladder overactivity. Urology. 2002 Nov;60(5 Suppl 1):22-6; discussion 27. doi: 10.1016/s0090-4295(02)01788-0.

  PMID: 12493346 BACKGROUND

• Michel MC, Chapple CR. Basic mechanisms of urgency: roles and benefits of pharmacotherapy. World J Urol. 2009 Dec;27(6):705-9. doi: 10.1007/s00345-009-0446-5.

  PMID: 19588154 BACKGROUND

• Ohtake A, Sato S, Sasamata M, Miyata K. The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: ameliorative effect of solifenacin succinate (Vesicare), a bladder-selective antimuscarinic agent, on overactive bladder symptoms, especially urgency episodes. J Pharmacol Sci. 2010;112(2):135-41. doi: 10.1254/jphs.09r13fm. Epub 2010 Feb 4.

  PMID: 20134114 BACKGROUND

• Hoffstetter S, Leong FC. Solifenacin succinate for the treatment of overactive bladder. Expert Opin Drug Metab Toxicol. 2009 Mar;5(3):345-50. doi: 10.1517/17425250902762866.

  PMID: 19331596 BACKGROUND

• Pelman RS, Capo JP Jr, Forero-Schwanhaeuser S. Solifenacin at 3 years: a review of efficacy and safety. Postgrad Med. 2008 Jul;120(2):85-91. doi: 10.3810/pgm.2008.07.1795.

  PMID: 18654073 BACKGROUND

• Haab F, Cardozo L, Chapple C, Ridder AM; Solifenacin Study Group. Long-term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome. Eur Urol. 2005 Mar;47(3):376-84. doi: 10.1016/j.eururo.2004.11.004. Epub 2005 Jan 5.

  PMID: 15716204 BACKGROUND

• Santos JC, Telo ER. Solifenacin: scientific evidence in the treatment of overactive bladder. Arch Esp Urol. 2010 Apr;63(3):197-213. English, Spanish.

  PMID: 20431184 BACKGROUND

• Oliver JD. The viable but nonculturable state in bacteria. J Microbiol. 2005 Feb;43 Spec No:93-100.

  PMID: 15765062 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

• Thomas-White KJ, Hilt EE, Fok C, Pearce MM, Mueller ER, Kliethermes S, Jacobs K, Zilliox MJ, Brincat C, Price TK, Kuffel G, Schreckenberger P, Gai X, Brubaker L, Wolfe AJ. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J. 2016 May;27(5):723-33. doi: 10.1007/s00192-015-2847-x. Epub 2015 Sep 30.

  PMID: 26423260 DERIVED

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Urinary Bladder, Overactive; Urinary Tract Infections

Interventions

Solifenacin Succinate

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; Infections

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Alan J. Wolfe
• Organization: Loyola University Chicago, Microbiology and Immunology

awolfe@luc.edu

224-392-4002

Study Officials

• Alan J Wolffe, PhD

  Loyola University Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Microbiology Immunology

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: July 17, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: December 7, 2015
• Results First Posted: December 7, 2015

Record last verified: 2015-10

Locations

US (1)