LURN: Urinary Urgency Phenotyping Protocol

Study Overview
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Brief Summary
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The purpose of this study is to define and characterize important subtypes of patients with urinary urgency to improve our understanding of the pathophysiology, risk factors, experiences, and comorbidities to lay the foundation for more effective treatment by focusing on the most bothersome and difficult to treat symptoms of urinary urgency and urgency urinary incontinence.

Detailed Description
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LURN is pursuing deeper phenotyping of patients with urinary urgency and UUI using distinct, but related, projects. The Urinary Urgency Phenotyping Protocol is the overarching effort, and will comprise five integrated projects. Project A, the Observational Cohort, will be a large-scale accrual of male and female participants with urinary urgency and age-matched controls without any LUTS. Standardized clinical data, comprising information typically gathered at the patient clinic encounter, self-report symptom, urologic and non-urologic data, and biosamples will be collected. Using this group of participants, subsets will be identified for more focused and in-depth studies of urinary urgency and urgency incontinence. This more focused effort will be conducted as Project B: the Central Sensitization Study; Project C: the Physical Activity and Sleep Study; Project D: the Organ-Based Study; and Project E: the Qualitative Assessment of Patients with Urinary Urgency Study.

Official Title
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Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Urinary Urgency Phenotyping Protocol

Conditions
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Lower Urinary Tract Symptoms

Intervention / Treatment
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* Other: Observational
* Other: Observational Controls
* Other: Central Sensitization
* Other: Physical Activity and Sleep Tracker
* Other: Physical Activity and Sleep Tracker Controls
* Other: Organ-Based
* Other: Qualitative Assessment of Patients with Urinary Urgency


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men presenting for evaluation or treatment of urinary urgency/ UUI to one of the LURN sites. These symptoms are not required to be the primary symptom(s) of presentation, but must be bothersome to the participant. Age ≥ 18 years. The presence of any of the urinary urgency or urgency incontinence symptoms based on responses to the LUTS Tool with a 1-month recall period (Appendix A) as follows: Answered sometimes, often, or always on either: During the past month, how often have you had a sudden need to rush to urinate?. Participants who answered never or rarely are not eligible since they are not deemed to have significant urinary urgency symptoms. How often have you had a sudden need to rush to urinate for the fear of leaking urine? Positive answer must also be associated with bother rating on that particular question of somewhat, quite a bit, or a great deal The ability to give informed consent and complete self-reported questionnaires electronically. Access to and willingness to utilize smart phone Exclusion Criteria: a. Clinical impression of bladder outlet obstruction (based on symptoms or urodynamics) as primary etiology of LUTS. b. Gross hematuria/self-reported gross or visible urine in the blood. c. Significant neurologic disease or injury, including but not limited to: cerebral vascular accident with residual defect, Alzheimer's dementia, Parkinson's disease, traumatic brain injury, spinal cord injury, complicated spinal surgery, multiple sclerosis. d. Primary complaint is pelvic pain. e. Diagnosis of interstitial cystitis, chronic prostatitis, or chronic orchalgia. f. Pelvic or endoscopic GU surgery within the preceding 6 months (not including diagnostic cystoscopy). g. Ongoing symptomatic urethral stricture. h. History of LUT or pelvic malignancy. i. Current chemotherapy or other cancer therapy. j. Pelvic device or implant complication (e.g., sling or mesh complications). k. In men, prostate biopsy in the previous 6 months. l. In women, current pregnancy or planned pregnancy during the follow-up period. m. History of cystitis caused by tuberculosis, radiation therapy, or Cytoxan/cyclophosphamide therapy. n. Augmentation cystoplasty or cystectomy. o. Presence of urinary tract fistula. p. Current major psychiatric disorder or other psychiatric or medical issues that would interfere with study participation (e.g., dementia, psychosis, etc.). q. Inability to relay valid information, actively participate in the study, or provide informed consent (includes uncontrolled psychiatric disease). r. Difficulty reading or communicating in English. s. No access to internet/smart phone. t. Indwelling Foley catheter/routine self-catheterization. u. In addition to the criteria listed above, pregnancy during the study will be a study end point.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective Observational Cohort Study<br>Men and women with lower urinary tract symptoms. | Other: Observational<br>* Treatment: Up to five interactions: In-person visits at Baseline, 3 months, and 12 months after initial visit, and phone/online interaction at 6 months and 9 months after initial visit. Each in-person follow up visit is expected to last up to 2 hours and each phone/online interaction is expected to last up to 1½ hours. Answering questions about your general health and urinary symptoms - may be done remotely Physical exam Completing Self- Reported Measures questionnaires - may be done remotely Completing voiding/intake and food diaries, either online or on paper Weekly text message survey regarding symptom and treatment changes Biosample collection: At baseline: Up to 4 tablespoons of whole blood, dried blood spots, and urine At baseline: Whole blood will be collected with other biospecimens At 3 months: Up to 4 tablespoons of blood, dried blood spots and urine At 12 months: Dried blood spots<br>|
| Prospective Observational Cohort Study Controls<br>Men and women who do not have urinary dysfunction. | Other: Observational Controls<br>* One in-person visit that is expected to last up to 2 hours Answering questions about your general health and urinary history Physical exam Completing Self- Reported Measures questionnaires Completing voiding/intake and food diaries, either online or on paper Biosample collection of up to 4 tablespoons of whole blood, dried blood spots, and urine<br>|
| Central Sensitization Study<br>Men and women enrolled in the Prospective Observational Cohort Study with urinary urgency. | Other: Central Sensitization<br>* One in-person visit expected to take up to 30 minutes, that include: Segmental Mechanical Hyperalgesia - a hand-held device with a small flat rubber surface will be placed above the pubic bone and forearm, and will apply pressure. Participant will be asked about the intensity and unpleasantness that they experience. Pinprick Temporal Summation - participant will receive tactile stimulation by a pointed skin probe (pinprick stimulator) being placed above the pubic bone and forearm. Participant will be asked to rate the sensation they are feeling. Current treatment information including prior surgery or procedures, medication use, other current treatment/therapy used at the time of the visit. Self-reported measures questionnaires<br>|
| Central Sensitization Study Controls<br>Men and women enrolled in the Prospective Observational Cohort Study with no symptoms of urinary urgency. | Other: Central Sensitization<br>* One in-person visit expected to take up to 30 minutes, that include: Segmental Mechanical Hyperalgesia - a hand-held device with a small flat rubber surface will be placed above the pubic bone and forearm, and will apply pressure. Participant will be asked about the intensity and unpleasantness that they experience. Pinprick Temporal Summation - participant will receive tactile stimulation by a pointed skin probe (pinprick stimulator) being placed above the pubic bone and forearm. Participant will be asked to rate the sensation they are feeling. Current treatment information including prior surgery or procedures, medication use, other current treatment/therapy used at the time of the visit. Self-reported measures questionnaires<br>|
| Physical Activity and Sleep Study<br>Men and women enrolled in the Prospective Observational Cohort Study with urinary urgency. | Other: Physical Activity and Sleep Tracker<br>* A physical activity and sleep monitor (Fitbit Charge 3 or similar) will be worn for a 2 week period starting at baseline prior to treatment and again at 3 months. During each 2 week period: The Fitbit will be worn both day and night to collect the most information. Text message reminders to wear the Fitbit will be sent. Daily text messages asking the number of nighttime voids you had.<br>|
| Physical Activity and Sleep Study Controls<br>Men and women enrolled in the Prospective Observational Cohort Study with no symptoms of urinary urgency. | Other: Physical Activity and Sleep Tracker Controls<br>* A physical activity and sleep monitor (Fitbit Charge 3 or similar) will be worn for a 2 week period at baseline prior to treatment. During the 2 week period: The Fitbit will be worn both day and night to collect the most information. Text message reminders to wear the Fitbit will be sent. Daily text messages asking the number of nighttime voids you had.<br>|
| Organ-Based Study<br>Women enrolled in the Prospective Observational Cohort Study with urinary urgency, with and without urgency incontinence. | Other: Organ-Based<br>* One in-person visit involving: Urethral vibratory sensation threshold Urethral Pressure Profilometry Cystometry Uroflowmetry Lidocaine Pre-Treatment Cystometry<br>|
| Organ-Based Study Controls<br>Women enrolled in the Prospective Observational Cohort Study with no symptoms of urinary urgency pr urgency incontinence. | Other: Organ-Based<br>* One in-person visit involving: Urethral vibratory sensation threshold Urethral Pressure Profilometry Cystometry Uroflowmetry Lidocaine Pre-Treatment Cystometry<br>|
| Qualitative Assessment of Patients with Urinary Urgency Study<br>Men and women enrolled in the Prospective Observational Cohort Study with urinary urgency who have treatment plans prescribed at the baseline visit. | Other: Qualitative Assessment of Patients with Urinary Urgency<br>* Participation will include two interviews with a research assistant over the phone and are expected to take up to 60 minutes for each interview. The first interview will be done within four weeks from enrollment, before the start of treatment. The interview will include questions about participant's urinary urgency, including symptoms experienced, the onset of symptoms and other factors that affect urgency. Approximately three months after the start treatment the participant will be interviewed again. This interview will cover changes in symptoms and experience with treatment, such as side effects and satisfaction with treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lower urinary tract symptoms | Participants will be classified as treatment responders if they achieve at least a 10-point reduction from baseline on the OAB-q and/or respond much better or very much better on the PGI-I | Baseline, 3 months, 6 month, 9 months,12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine the presence of sensory hypersensitivity in urinary urgency (with or without urgency incontinence) | Participants will rate pain intensity and unpleasantness on 0-100 numeric rating scales when ascending pressure is applied to the suprapubic area using a hand-held algometer | Baseline | 
| Assess the relationship between physical activity and sleep quality in men and women with bothersome urinary urgency | Participants will wear a mobile tracker for two weeks at baseline and at 3 months to capture the average number of steps per 24 hours and number of nocturnal voids | Baseline and 3 months | 
| The role of the urethra and its interaction with the bladder in LUT function and dysfunction | Urodynamic studies will be performed on urethra and bladder to assess urethral closure pressure, urethral sensation, and bladder volume | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overactive Bladder, Urinary Urgency, Lower Urinary Tract Dysfunction, Lower Urinary Tract Symptoms, Bladder Symptoms