Symptoms of Lower Urinary Tract Dysfunction Phenotyping Study

Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Phenotyping Study Protocol

The purpose of this study is to advance our understanding of people who experience urinary and bladder problems. We are interested in learning about people's experiences with urinary symptoms and how these symptoms will be managed. We want to understand the important differences among people and what factors affect urinary and bladder problems. After all of the information is collected, we will have a better understanding of how to improve the care and treatment for people who have urinary and bladder problems.

The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to advance our understanding of lower urinary tract dysfunction (LUTD) in women and men. LUTD is a term intended to be comprehensive and to challenge current paradigms about how symptomatic pelvic disorders are defined as 'diseases.' Lower urinary tract symptoms (LUTS) are likely caused and exacerbated by a variety of factors and thus do not represent the manifestation of a single disease. Clinical management of LUTD, including treatment outcomes, remains suboptimal since the biological and psychosocial factors that initiate, exacerbate, and modify this group of symptoms remain largely unknown. As an initial effort to better characterize the biological and psychosocial factors that initiate, exacerbate, and modify LUTS, the LURN investigators will establish a prospective Observational Cohort Study of men and women with LUTS presenting for the first time to LURN physicians.

Information to be obtained from study participants initially (at time of enrollment) includes a standardized clinical examination, medical history, select testing of the lower urinary tract, and participants' self-report of LUTS, pelvic floor symptoms including sexual function and bowel symptoms, depression, anxiety, sleep patterns, stress, metabolic risk factors, and health-related quality of life. We will also collect serum, urine, saliva, and perineal swabs from men and vaginal swabs from women for storage at the NIDDK Sample Repository for future study by the LURN investigators and the broader research community. This information will be used to construct subgroups of patients who have similar symptoms, clinical presentations, comorbidities, pelvic floor dysfunctions, and psychological profiles. These patient characteristics and behaviors likely affect the evaluation, diagnosis, and/or treatment of LUTS. Additional information will be collected 3 months and 12 months after enrollment or 3 and 12 months after surgery for patients receiving surgical treatment, and will include an interval clinical history, participants' self-report of LUTS, pelvic floor symptoms including sexual function and bowel symptoms, depression, anxiety, and health-related quality of life. We will also collect biological samples at 3 and 12 months after enrollment.

The LURN Neuroimaging and Sensory Testing component of the study will investigate abnormal sensation of the lower urinary tract at the level of the organism. Subjects and controls will have a one-time visit soon after their baseline visit, where they will undergo an fMRI scan of their brain and multimodal quantitative sensory testing assessing perceptual responses to physical stimuli (pain and sound).

The information to be collected from the prospective Observational Cohort Study will be limited and not sufficient to fully understand the pathophysiology and biology of LUTS. Therefore, the Observational Cohort Study will serve as the basis for further LURN studies. The long-term goal of the LURN is to better characterize patients with LUTD in order to advance future research on the pathophysiology of these

Inclusion Criteria:

1. Men and women presenting for new patient visits for evaluation or treatment of LUTS to one of the LURN physicians.
2. Age ≥ 18 years.
3. The presence of any of the symptoms reported in Table 1, based on responses to the LUTS Tool with a one month recall period.
4. The ability to give informed consent and complete self-reported questionnaires electronically.

Table 1: LUTS Appropriate for Study Inclusion

• Daytime frequency
• Nocturia
• Urgency
• Incontinence/leakage (various types)
• Poor or absent sensation of bladder filling
• Slow/weak stream
• Splitting or spraying
• Intermittent stream/Double voiding
• Hesitancy
• Straining
• Dribbling at the end of flow
• Paruesis (shy bladder syndrome)
• Poor or absent sensation of urethra during void
• Feeling of incomplete emptying
• Post-micturition dribble (delayed)
• Abnormal bladder or urethral sensations

Exclusion Criteria:

1. Gross hematuria.
2. 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.
3. Primary complaint is pelvic pain.
4. Diagnosis of interstitial cystitis, chronic prostatitis, or chronic orchialgia.
5. Pelvic or endoscopic GU surgery within the preceding 6 months (not including diagnostic cystoscopy).
6. Current sexually transmitted infection. (deferral; subject can enroll after negative culture)
7. Ongoing symptomatic urethral stricture.
8. History of lower urinary tract or pelvic malignancy.
9. Current chemotherapy or other cancer therapy.
10. Pelvic device or implant complication (e.g., sling or mesh complications).
11. Current functioning neurostimulator.
12. Botox injection to the bladder or pelvic structures within the preceding 12 months.
13. In men, prostate biopsy in the previous 3 months.
14. In women, pregnancy.
15. History of cystitis caused by tuberculosis, radiation therapy, or Cytoxan/cyclophosphamide therapy.
16. Augmentation cystoplasty or cystectomy.
17. Presence of urinary tract fistula.
18. Current major psychiatric disorder or other psychiatric or medical issues that would interfere with study participation (e.g., dementia, psychosis, etc.).
19. Inability to relay valid information, actively participate in the study, or provide informed consent (includes uncontrolled psychiatric disease).
20. Difficulty reading or communicating in English.