Bacterial Genomic Sequencing in Overactive Bladder

Overactive Bladder Clinical Trial

Official title:

The Effect of Short Term Solifenacin for Overactive Bladder on the Female Urinary Microbiome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01642277
• Other study ID #: 204195
• Status: Completed
• Phase: Phase 2
• First received: July 3, 2012
• Last updated: October 30, 2015
• Start date: July 2012
• Est. completion date: August 2014

Study information

• Verified date: October 2015
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

This is a prospective study with two groups: Women who have accepted a clinical recommendation for OAB treatment with solifenacin and a comparator (control) group of women unaffected by OAB. All women will have a baseline urine assessment with bacterial genome sequencing. Solifenacin treated patients will also have urine assessments with bacterial genomic sequencing at 4 and 12 weeks on treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: August 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

• 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Overactive Bladder
• Urinary Bladder, Overactive

Intervention

Drug:
• Solifenacin
5 mg for 4 weeks with option to increase to 10 mg for an additional 8 weeks

Locations

Country	Name	City	State
United States	Loyola University Chicago Health Sciences Division	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Astellas Pharma US, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. Review. — View Citation

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. Epub 2005 Jan 5. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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 . Review. — View Citation

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. — View Citation

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. Review. — View Citation

Mostwin JL. Pathophysiology: the varieties of bladder overactivity. Urology. 2002 Nov;60(5 Suppl 1):22-6; discussion 27. Review. — View Citation

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. Epub 2010 Feb 4. Review. — View Citation

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

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. Review. — View Citation

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. — View Citation

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

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bacterial Genomic Sequencing	Participants were classified into Low Biomass, Lactobacillus, Gardnerella, Diverse, and Other urotypes based on the bacterial DNA at baseline.	12 weeks	No
Secondary	Assessment of Overactive Bladder Questionnaire (OABQ)	The Overactive Bladder Questionnaire (OAB-q) was developed to assess symptom bother and the impact of overactive bladder (OAB) on health-related quality of life (HRQL). The instrument comprises 33 items. Response options for the symptom frequency and HRQL items are presented as 6-point Likert scales ranging from 'none of the time' to 'all of the time' for symptom frequency (and 'not at all' to 'a very great deal' for symptom bother). From these 33 items, six sub-scales are assessed separately: (1) OAB symptom severity, (2) Coping with OAB symptoms, (3) Concern for OAB symptoms, (4) Sleep as a function of OAB symptoms, (5) Social functioning as a consequence of OAB symptoms, and (6) Health related quality of life (HRQL) as a function of OAB symptoms. Each sub-scale score ranges from 0 to 100 (where higher scores indicate more severe OAB symptoms and lower scores indicate minimal symptom severity).	End of study (Week 12)	No
Secondary	Assessment of Pelvic Floor Disease Inventory (PFDI) Questionnaire	The PFDI comprises 46 items on a 4-point symptom severity scale ranging from 1 = "Not at all" to 4 = "Quite a bit". From these items, 13 separate sub-scales are reported: (1) Obstructive discomfort, (2) Irritation, (3) Stress resulting from urinal distress, (4) A general sub-scale for pelvic organ prolapse distress, (5) An anterior sub-scale for pelvic organ prolapse distress, (6) A posterior sub-scale for pelvic organ prolapse distress, (7) An obstructive sub-scale for colorectal anal distress, (8) Incontinence, (9) Pain, and (10) A rectal prolapse sub-scale for colorectal anal distress. For each of these sub-scales, scores from from 0 to 100 (where higher scores indicate greater symptom severity). There are three additional sub-scales: (11) The urinary distress inventory, (12) The pelvic organ distress inventory, and (13) The colorectal distress inventory. Each of these ranges from 0 to 400 (with higher scores indicating greater symptom severity).	12 weeks	No