Urgency Urinary, Urinary Incontinence
Conditions
Keywords
Urinary Incontinence, Urgency Urinary, Anticholinergic Treatment, Urinary Microbiome
Brief summary
Urinary incontinence (UI) is a very common condition affecting women of all ages. The objective of this pilot study is to better understand the urinary microbiome and associated inflammatory markers in blood and urine in women with urgency UI. The study will assess how inflammation may affect response to standard of care anticholinergic medication treatment for urgency urinary incontinence.
Detailed description
This study is designed as a prospective pilot study of women presenting to the Urogynecology clinic with urgency urinary incontinence symptoms who are offered treatment with a standard of care anticholinergic medication for six weeks. The patient will be asked to provide a catheterized urine sample at baseline and 6 weeks and blood draw only at baseline. Study participants will fill out a Urinary Distress Inventory-6 (UDI-6) questionnaire at baseline and fill a bladder diary for 48 hours before starting the anticholinergic medication. The urine will be assessed by standard and enhanced urine cultures and DNA amplification and 16S rRNA sequencing for urinary microbiome along with inflammatory markers in the urine. Inflammatory markers in both the blood and urine will be measured using immunoenzyme assays. Measurements for microbiome will be repeated for all patients at 6 weeks. Baseline urinary symptoms at enrollment and variation of symptoms after 6 weeks of anticholinergic treatment will be assessed using the UDI-6 questionnaire and a bladder diary.
Interventions
DRUGOxybutynin, Solifenacin, Tolterodine, Trospium, or Fesoterodine
Study participants will be evaluated for urgency urinary incontinence and will be offered treatment with a standard of care anticholinergic medication for 6 weeks. All study participants will fill out the UDI-6 and two day bladder diary at baseline before starting anticholinergic medication treatment. Participants will then provide a urine sample and blood draw to be assessed for urinary microbiome and inflammation. Anticholinergic medication will be taken daily for 6 weeks and the same procedures (UDI-6 questionnaire, bladder diary, urine sample except the blood draw for assessment) will be performed at the 6-week time period.
Sponsors
Medical University of Silesia
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postmenopausal (Age ≥ 50) women with Urgency Urinary Incontinence (UUI) * English speaking * Willing to take anticholinergics for at least 6 weeks * Willing to complete UDI-6 and voiding diary at baseline and 6 weeks * Willing to give urine and blood for study at baseline and 6 weeks
Exclusion criteria
* Have taken anticholinergic medication within the last month * Have taken antibiotics within the last month * Urinary Tract Infection (UTI) in the last three months * Neurological disease (eg. Parkinson's disease, Multiple Sclerosis, etc.) * Immunological deficiencies * History of sexually transmitted disease (STD) * Lack of consent * Not ambulatory (e.g. uses a wheelchair)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline and 6 weeks | Statistical testing was used to determine if there was a difference in inflammatory markers in the urine of patients between baseline visit and 6 week visit. 7 markers were chosen and compared, all inflammatory markers present in urine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effectiveness of Anticholinergic Treatment in Relation to the Urinary Microbiome. Culture to Standard Culture Media Will Pickup Aerobic Bacteria and Yeasts After DNA Extraction and End Point PCR for 16S rDNA Genes. | At the 6 week mark | The change in g\_lactobacillus from Baseline to Follow-up (6 weeks), which corresponds to before and after anticholinergic treatment. |
| The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms. | Baseline visit (0 weeks) | Symptoms taken from the UDI-6, a validated questionnaire for urogynecologic symptoms, were gathered at baseline for all patients. Duration of Urinary Incontinence symptoms is presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Anticholinergic Treatment Women presenting to the Urogynecology clinic with urgency urinary incontinence symptoms will receive standard of care anticholinergic treatment and will have their urinary microbiome evaluated before and after treatment
Oxybutynin, Solifenacin, Tolterodine, Sanctura or Toviaz: Study participants will be evaluated for urgency urinary incontinence and will be offered treatment with a standard of care anticholinergic medication for 6 weeks. All study participants will fill out the UDI-6 and two day bladder diary at baseline before starting anticholinergic medication treatment. Participants will then provide a urine sample and blood draw to be assessed for urinary microbiome and inflammation. Anticholinergic medication will be taken daily for 6 weeks and the same procedures (UDI-6 questionnaire, bladder diary, urine sample except the blood draw for assessment) will be performed at the 6-week time period. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Standard of Care Anticholinergic Treatment |
|---|---|
| Age, Continuous | 64 years |
| Alcohol Use Alcohol use | 11 Participants |
| Alcohol Use No alcohol use | 9 Participants |
| Caffeine Use Caffeine use | 17 Participants |
| Caffeine Use No caffeine use | 3 Participants |
| Comorbidities Arthritis | 3 Participants |
| Comorbidities Asthma/COPD | 4 Participants |
| Comorbidities Depression/anxiety | 6 Participants |
| Comorbidities Diabetes | 4 Participants |
| Comorbidities Heart disease | 1 Participants |
| Comorbidities Hypertension | 8 Participants |
| Comorbidities Liver Disease | 0 Participants |
| Comorbidities None | 11 Participants |
| Comorbidities Renal Disease | 0 Participants |
| Comorbidities Stroke | 1 Participants |
| Comorbidities Thyroid Disease | 2 Participants |
| Contraceptive Use Current contraceptive use | 2 Participants |
| Contraceptive Use No contraceptive use | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| HRT/Vaginal Estrogen Use Hormone Replacement Therapy (HRT)/Vaginal Estrogen Use | 4 Participants |
| HRT/Vaginal Estrogen Use No HRT/Vaginal Estrogen Use | 16 Participants |
| Menopausal Status Post-menopausal | 17 Participants |
| Menopausal Status Pre-menopausal | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
| Smoking Status Current smoker | 0 Participants |
| Smoking Status Never-smoker | 12 Participants |
| Smoking Status Past-smoker | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu.
Statistical testing was used to determine if there was a difference in inflammatory markers in the urine of patients between baseline visit and 6 week visit. 7 markers were chosen and compared, all inflammatory markers present in urine.
Time frame: Baseline and 6 weeks
Population: 20 patients were involved in the study, however only 13 returned for follow-up, hence 13 patients involved in follow-up group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline GM-CSF | 0.102 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline CRP | 2.192 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up CRP | 2.565 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline IL-12/IL-23p40 | 2.192 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up IL-12/IL-23p40 | 2.565 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline MCP-1 | 75.49 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up MCP-1 | 65.02 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up GM CSF | 0.203 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline IL-1B | 0.203 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up IL-1B | 0.415 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline IL-6 | 0.667 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up IL-6 | 0.967 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Baseline IL-8 | 7.211 pg/mL |
| Standard of Care Anticholinergic Treatment | Inflammatory Markers in Urine Will be Measured Using Immunoenzyme Assays to Measure the Interaction of Anticholinergic Treatment and the Inflammatory Milieu. | Follow-up IL-8 | 6.116 pg/mL |
Comparison: T-test of Wilcoxon rank sum was used to test this non-normal data. Null hypothesis is that the concentration of urine inflammatory markers is the same at baseline and follow-up. This p-value is the probability that the difference in the CRP Calc. Conc. (pg/ml) between baseline and follow-up.p-value: 0.6497Wilcoxon (Mann-Whitney)
Comparison: T-test of Wilcoxon rank sum was used to test this non-normal data. Null hypothesis is that the concentration of urine inflammatory markers is the same at baseline and follow-up. This p-value is the probability that the difference in the IL-12/IL-23p40 Calc. Conc. (pg/ml) between baseline and follow-up.p-value: 0.4281Wilcoxon (Mann-Whitney)
Comparison: The null hypothesis is that the baseline and follow-up levels of the urine inflammatory markers are due to chance. This p-value represents the probability that the difference between the baseline and follow-up levels of MCP-1 Calc. Conc. (pg/ml) is due to chance.p-value: 0.3157Wilcoxon (Mann-Whitney)
Comparison: This p-value represents the probability that the difference between baseline and follow-up levels of GM-CSF Calc. Conc. (pg/ml) is due to chance.p-value: 0.1463Wilcoxon (Mann-Whitney)
Comparison: The null hypothesis is that the baseline and follow-up levels of the urine inflammatory markers are due to chance. This p-value represents the probability that the difference between the baseline and follow-up levels of IL-1β Calc. Conc. (pg/ml) is due to chance.p-value: 0.6091Wilcoxon (Mann-Whitney)
Comparison: The null hypothesis is that the baseline and follow-up levels of the urine inflammatory markers are due to chance. This p-value represents the probability that the difference between the baseline and follow-up levels of IL-6 Calc. Conc. (pg/ml) is due to chance.p-value: 0.3011Wilcoxon (Mann-Whitney)
Comparison: The null hypothesis is that the baseline and follow-up levels of the urine inflammatory markers are due to chance. This p-value represents the probability that the difference between the baseline and follow-up levels of IL-8 Calc. Conc. (pg/ml) is due to chance.p-value: 0.5009Wilcoxon (Mann-Whitney)
Secondary
The Effectiveness of Anticholinergic Treatment in Relation to the Urinary Microbiome. Culture to Standard Culture Media Will Pickup Aerobic Bacteria and Yeasts After DNA Extraction and End Point PCR for 16S rDNA Genes.
The change in g\_lactobacillus from Baseline to Follow-up (6 weeks), which corresponds to before and after anticholinergic treatment.
Time frame: At the 6 week mark
Population: The median change in g\_lactobacillus for patients who had both baseline and follow-up samples analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Anticholinergic Treatment | The Effectiveness of Anticholinergic Treatment in Relation to the Urinary Microbiome. Culture to Standard Culture Media Will Pickup Aerobic Bacteria and Yeasts After DNA Extraction and End Point PCR for 16S rDNA Genes. | 0.001131599 pg/mL |
Secondary
The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms.
Symptoms taken from the UDI-6, a validated questionnaire for urogynecologic symptoms, were gathered at baseline for all patients. Duration of Urinary Incontinence symptoms is presented.
Time frame: Baseline visit (0 weeks)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care Anticholinergic Treatment | The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms. | <6 months | 8 Participants |
| Standard of Care Anticholinergic Treatment | The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms. | 6-23 monts | 7 Participants |
| Standard of Care Anticholinergic Treatment | The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms. | 2-4 years | 4 Participants |
| Standard of Care Anticholinergic Treatment | The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms. | 5-10 years | 0 Participants |
| Standard of Care Anticholinergic Treatment | The Urogenital Distress Inventory (UDI-6) Questionnaire Will be Used to Assess Baseline Urinary Symptoms Prior to Anticholinergic Treatment. Participants Indicate How Long They Have Had These Symptoms. | >10 years | 1 Participants |