Bacterial Genomic Sequencing in Overactive Bladder

• Sponsor: Loyola University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01642277
• Collaborator: Astellas Pharma US, Inc. (Industry)
• Enrollment: 134
• Location: 1
• Arms: 2
• Duration (Months): 25
• Patients Per Site Per Month: 5.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Drug: Solifenacin	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: The Effect of Short Term Solifenacin for Overactive Bladder on the Female Urinary Microbiome
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Women using Solifenacin for OAB treatment Solifenacin treated women: Women with OAB who are prescribed solifenacin	Drug: Solifenacin; 5 mg for 4 weeks with option to increase to 10 mg for an additional 8 weeks; Other Names: Vesicare
No Intervention: Control: Women without OAB Women without OAB who are not prescribed solifenacin.

Outcome Measures

Primary Outcome Measures

1. Bacterial Genomic Sequencing [12 weeks]

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

Secondary Outcome Measures

1. Assessment of Overactive Bladder Questionnaire (OABQ) [End of study (Week 12)]

   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).

2. Assessment of Pelvic Floor Disease Inventory (PFDI) Questionnaire [12 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola University Chicago Health Sciences Division	Maywood	Illinois	United States	60153

Sponsors and Collaborators

• Loyola University
• Astellas Pharma US, Inc.

Investigators

• Principal Investigator: Alan J Wolffe, PhD, Loyola University Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Mostwin JL. Pathophysiology: the varieties of bladder overactivity. Urology. 2002 Nov;60(5 Suppl 1):22-6; discussion 27. Review.
• 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.
• Oliver JD. The viable but nonculturable state in bacteria. J Microbiol. 2005 Feb;43 Spec No:93-100. Review.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Alan J. Wolfe, Professor, Microbiology Immunology, Loyola University
• ClinicalTrials.gov Identifier: NCT01642277
• Other Study ID Numbers: 204195
• First Posted: Jul 17, 2012
• Last Update Posted: Dec 7, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Alan J. Wolfe, Professor, Microbiology Immunology, Loyola University: Overactive Bladder; OAB; Urinary Tract Infection; UTI; Microbiome; Bacteria; Solifenacin; 16S rRNA sequence
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Solifenacin Succinate

Study Results

Participant Flow

Recruitment Details	Recruitment began on July 16th, 2012 and ended on May 22nd, 2014 (i.e., 22.2 months). Participants were recruited during their outpatient appointments to the Urogynecology Clinic at Loyola University Medical Center (Maywood, IL) by a member of the research team.
Pre-assignment Detail	This was a 12-week open label study with no randomization scheme. Following diagnosis, patients were administered 5 mg daily solifenacin. At the 4-week visit, if a participant's symptoms were adequately controlled (response), she continued at dose for the study duration. If a participant reported no improvement, the dose was increased to 10 mg.

Arm/Group Title	Urinary Urge Incontinence	Non-Urinary Urge Incontinence
Arm/Group Description	Seventy-four (n = 74) women received 5-10mg daily solifenacin for the treatment of urinary urge incontinence (UUI).	Sixty (n = 60) women without UUI were evaluated at baseline only (week 0) in order to serve as a control cohort. These women never received study therapy (i.e., 5-10mg daily solifenacin).
Period Title: Overall Study
STARTED	74	60
COMPLETED	50	60
NOT COMPLETED	24	0

Baseline Characteristics

Arm/Group Title	Urinary Urge Incontinence	Non-Urinary Urge Incontinence	Total
Arm/Group Description	Seventy-four (n = 74) women received 5mg daily solifenacin (with an option to increase to 10mg daily solifenacin at 4 weeks) for the treatment of urinary urge incontinence (UUI).	Sixty (n = 60) women without UUI were evaluated at baseline only (week 0) in order to serve as a control cohort. These women never received study therapy (i.e., 5-10mg daily solifenacin).	Total of all reporting groups
Overall Participants	74	60	134
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.5 (11.5)	49 (14.7)	56.04 (14.34)
Sex: Female, Male (Count of Participants)
Female	74 100%	60 100%	134 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	56 75.7%	43 71.7%	99 73.9%
Black	13 17.6%	12 20%	25 18.7%
Asian	0 0%	1 1.7%	1 0.7%
Hispanic	5 6.8%	4 6.7%	9 6.7%
Region of Enrollment (participants) [Number]
United States	74 100%	60 100%	134 100%
Body Mass Index (kg/m2) [Median (Standard Deviation) ]
Median (Standard Deviation) [kg/m2]	32.7 (8.4)	27.9 (5.5)	30.59 (7.61)
Vaginal Parity (Births) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Births]	2.00	2.00	2.00
Estrogen Status (participants) [Number]
Negative	7 9.5%	32 53.3%	39 29.1%
Positive	65 87.8%	26 43.3%	91 67.9%
Unknown	2 2.7%	2 3.3%	4 3%
Diabetes (participants) [Number]
No	67 90.5%	58 96.7%	125 93.3%
Yes	7 9.5%	2 3.3%	9 6.7%
Hypertension (participants) [Number]
No	48 64.9%	49 81.7%	97 72.4%
Yes	26 35.1%	11 18.3%	37 27.6%
Coronary Artery Disease (participants) [Number]
No	65 87.8%	59 98.3%	124 92.5%
Yes	9 12.2%	1 1.7%	10 7.5%
Smoking (participants) [Number]
Non-Smoker	68 91.9%	56 93.3%	124 92.5%
Smoker	6 8.1%	4 6.7%	10 7.5%
Marital Status (participants) [Number]
Married	38 51.4%	37 61.7%	75 56%
Separated	3 4.1%	1 1.7%	4 3%
Divorced	9 12.2%	6 10%	15 11.2%
Widowed	14 18.9%	1 1.7%	15 11.2%
Single	10 13.5%	15 25%	25 18.7%
Prior Treatment for OAB (participants) [Number]
Prior Treatment	37 50%	0 0%	37 27.6%
No prior treatment	37 50%	60 100%	97 72.4%
Sequencing Urotypes at Baseline (participants) [Number]
Low biomass	37 50%	34 56.7%	71 53%
Lactobacillus urotype	15 20.3%	16 26.7%	31 23.1%
Diverse urotype	8 10.8%	4 6.7%	12 9%
Gardnerella urotype	8 10.8%	4 6.7%	12 9%
Other urotypes	6 8.1%	2 3.3%	8 6%

Outcome Measures

1. Primary Outcome

Title	Bacterial Genomic Sequencing
Description	Participants were classified into Low Biomass, Lactobacillus, Gardnerella, Diverse, and Other urotypes based on the bacterial DNA at baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

This was a completer analysis comprising participants who completed 12 weeks of treatment (n = 50).

Arm/Group Title	Urinary Urge Incontinence
Arm/Group Description	Women who received 5-10mg daily solifenacin for the treatment of urinary urge incontinence (UUI).
Measure Participants	50
Low biomass	25 33.8%
Lactobacillus urotype	11 14.9%
Diverse urotype	3 4.1%
Gardnerella urotype	6 8.1%
Other urotypes	3 4.1%

2. Secondary Outcome

Title	Assessment of Overactive Bladder Questionnaire (OABQ)
Description	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).
Time Frame	End of study (Week 12)

Outcome Measure Data

Analysis Population Description

Participants who received solifenacin were asked to complete the OABQ at 12 weeks in order to assess overactive bladder symptoms.

Arm/Group Title	Solifenacin Responder	Solifenacin Non-Responder
Arm/Group Description	Individuals with urinary urge incontinence who responded to solifenacin at 12 weeks	Individuals with urinary urge incontinence who did not respond to solifenacin at 12 weeks
Measure Participants	37	13
Symptom Severity Score	17.50	37.50
Coping Score	92.50	80.00
Concern Score	97.14	82.86
Sleep Score	92.00	84.00
Social Score	100.00	96.00
Health Related Quality of Life (HRQL)	92.80	76.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For symptom-severity score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size and non-normal distributions of symptom severity scores. The null hypothesis is that there is no difference between the two groups in symptom severity, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) symptom severity than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.052
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For coping score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size, non-normal distributions, and outliers of coping scores. The null hypothesis is that there is no difference between the two groups in coping, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) coping than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the concern score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size, non-normal distributions, and outlier of the concern scores. The null hypothesis is that there is no difference between the two groups in their concern, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) concern than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	2.176
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the sleep score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size, non-normal distributions, and outliers of sleep scores. The null hypothesis is that there is no difference between the two groups in sleep scores, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) sleep scores than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For social score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size, non-normal distributions, and outliers of social scores. The null hypothesis is that there is no difference between the two groups in social scores, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) social scores than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	2.02
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the overall health related quality of life (HRQL) score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size, non-normal distributions, and outliers of HRQL scores. The null hypothesis is that there is no difference between the two groups in health related quality of life, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) health realted quality of life than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	2.03
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Assessment of Pelvic Floor Disease Inventory (PFDI) Questionnaire
Description	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).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received solifenacin were asked to complete the PFDI questionnaire at 12 weeks in order to assess certain bowel, bladder, and pelvic symptoms.

Arm/Group Title	Solifenacin Responder	Solifenacin Non-Responder
Arm/Group Description	Individuals with urinary urge incontinence who responded to solifenacin at 12 weeks	Individuals with urinary urge incontinence who did not respond to solifenacin at 12 weeks
Measure Participants	37	13
Obstructive Discomfort Score	5.77	7.69
Irritative Score	12.50	32.50
Stress Score	8.33	16.67
Urinary Distress Inventory Score	40.19	60.26
General Score	7.14	14.29
Anterior Score	8.33	8.33
Posterior Score	0	16.67
Pelvic Organ Prolapse Distress Inventory Score	20.83	47.62
Obstructive Score	0	16.67
Pain Irritation Score	10.71	10.71
Rectal Prolapse	0	0
Colo-Rectal-Anal Distress Inventory Score	17.86	42.86
Incontinence Score	0	10.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the obstructive discomfort score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in obstructive discomfort, and and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) obstructive discomfort than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.46
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the irritative score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in irritation, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) irritation than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.07
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.80
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the stress score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in stress, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) stress than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.11
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.59
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the urinary distress inventory score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in urinary distress, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) urinary distress than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.69
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the general score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in general pelvic floor disease severity, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) general pelvic floor disease severity than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.68
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the anterior score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in anterior pelvic floor disease severity, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) anterior pelvic floor disease severity than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.82
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the posterior score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in posterior pelvic floor disease severity, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) posterior pelvic floor disease severity than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.06
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Urinary Urge Incontinence, Solifenacin Non-Responder
	Comments	For the pelvic organ prolapse distress score, the non-parametric Mann-Whitney test was used to compare the responder and non-responder groups due to low sample size in the non-responder group (n = 13). The null hypothesis is that there is no difference between the two groups in pelvic organ prolapse distress, and the two-sided alternative hypothesis is that one of the two groups has higher (or lower) pelvic organ prolapse distress than the other group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.07
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Standardized test statistic (z-score)
	Estimated Value	-1.85
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Participants who received solifenacin were assessed for adverse events over 12 weeks. Control participants who did not receive solifenacin, however, were only seen at baseline (0 weeks).
Arm/Group Title	Urinary Urge Incontinence		Non-Urinary Urge Incontinence
Arm/Group Description	Seventy-four (n = 74) women received 5-10mg daily solifenacin for the treatment of urinary urge incontinence (UUI).		Sixty (n = 60) women without UUI were evaluated at baseline only (week 0) in order to serve as a control cohort. These women never received study therapy (i.e., 5-10mg daily solifenacin).
All Cause Mortality
	Urinary Urge Incontinence		Non-Urinary Urge Incontinence
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Urinary Urge Incontinence		Non-Urinary Urge Incontinence
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Urinary Urge Incontinence		Non-Urinary Urge Incontinence
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/74 (13.5%)		0/0 (NaN)
Gastrointestinal disorders
Constipation	4/74 (5.4%)	4	0/0 (NaN)	0
General disorders
Dry Mouth	3/74 (4.1%)	3	0/0 (NaN)	0
Elevated Blood Pressure	1/74 (1.4%)	1	0/0 (NaN)	0
Dizziness	1/74 (1.4%)	1	0/0 (NaN)	0
Immune system disorders
Hives	1/74 (1.4%)	1	0/0 (NaN)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.