Pilot Trial Of Urinary Nerve Growth Factor (NGF) As Biomarker for Male Lower Urinary Tract Symptoms

Study Overview
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Brief Summary
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A single center, pilot trial using tamsulosin and solifenacin in 10 men with symptomatic lower urinary tract symptoms (LUTS). Subjects will be evaluated at baseline, 1, 2, and 3 months for urinary NGF, urine creatinine, NGF/CR ratio and patient reported outcomes through questionnaires.

Detailed Description
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Single center, pilot trial, single arm study using once daily dosing of tamsulosin and solifenacin in 10 men with symptomatic lower urinary tract symptoms (LUTS). Assessments occur at Baseline, 1 Month, 2 Month and 3 Month to evaluate: urinary NGF (pg/mL), urine creatinine (mg/dL), NGF/Cr ratio and patient reported questionnaire outcomes (AUA Symptom Score/IPSS, Patient Perception of Bladder Condition, Patient Perception of Urge Intensity 'PPIUS', LUTS Urinary Symptoms and Quality of Life). Each participant is assessed from baseline to Month 3 measurements. Protection of human subjects will be provided through the Houston Methodist Research Institute Institutional Review Board (see appendix 2). All men will receive morning dosing with Tamsulosin 0.4 mg (1 tab) and Solifenacin 5 mg (1 tab) orally at the same time.

Official Title
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Urinary Nerve Growth Factor as a Biomarker for Medical Treatment of Male Lower Urinary Tract Symptoms: A Pilot Trial

Conditions
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Lower Urinary Tract Symptoms

Intervention / Treatment
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* Drug: Tamsulosin
* Drug: Solifenacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men > 45 years old with symptomatic LUTS (clinical benign prostatic hypertrophy/BPH) International Prostate Symptom Score (IPSS) > 8 PSA < 10 ng/ml (negative biopsies within 6 months for any age-specific PSA elevation suspicious for prostate carcinoma) Post void residual urine < 150 mls Urinary Flow rate > 15 mL/sec Exclusion Criteria: Neurogenic bladder Urinary tract infection, Urinary stone(s), Urinary tract tumor Radiation therapy for urologic malignancy or prostate surgery; radiation to pelvic, colon, rectum, prostate, bladder, uterus or ovaries Alpha blocker therapy or anticholinergic therapy within 3 months of entry or 5 alpha reductase therapy within 18 months. History of cataracts with planned surgery

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: One (single arm)<br>All men will receive morning dosing with Tamsulosin (Flomax) 0.4 mg (1 tab) and Solifenacin (Vesicare) 5 mg (1 tab) orally at the same time. | Drug: Tamsulosin<br>* Alpha blocker used to in the treatment of urinary difficulties related to enlarged prostate or symptomatic benign prostatic hypertrophy. All men will receive Tamsulosin (Flomax®) 0.4 mg, 1 tab, per morning with Solifenacin (Vesicare®).<br>* Other names: tamsulosin hydrochloride, tamsulosin HCl, Flomax®;Drug: Solifenacin<br>* Antispasmodic/anticholinergic used to treat overactive bladder. All men will receive Solifenacin (Vesicare®) 5 mg, 1 tab, per morning with Tamsulosin.<br>* Other names: solifenacin succinate, VESIcare®, Vesicare®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.3/Wk12 | Urine sample tested for urinary Nerve Growth Factor (uNGF as measured in pg/mL), a small secreted protein in the bladder that supports bladder function regulation, at baseline (pre-dose) and week 12/Month 3 post-dose, after using daily tamsulosin and solifenacin. | Change from baseline to week 12 (3 months) | 
| Change From Baseline in Urinary Growth Factor to Creatinine Ratio (GF/Cr) | The urinary growth factor (GF) to creatinine ratio may be potential biomarker for overactive bladder, based on published articles. Measuring the ratio at baseline and Month 3, comparing the difference after treatment with tamsulosin and solifenacin which may provide insight into how lower urinary tract symptoms in men progresses. | change from baseline score to Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Post Void Residual (mL) at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 | Urine sample tested for urinary post void residual (measured in mL) at baseline (pre-dose), Month 1 and Month 2and week 12/Month 3 post-dose, post dose w/tamsulosin and solifenacin. | Change from baseline to months 1, 2 and 3 | 
| Change in Maximum Urinary Flow Rate (ml/s) at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 | Urination flow rate (measured in milliliters per second) at baseline (pre-dose), and Month 1, Month 2, and Month 3/Week 12 pose-dosing with tamsulosin and solifenacin. An average maximum urinary flow rate in males is 21 ml/sec aged 14-45 years-old and 12 ml/sec in males aged 46-65 years-old. | Change from baseline to months 1, 2 and 3 | 
| Change in IPSS-International Prostate Score Scale at Baseline Compared to Post Dose Survey at Month 1, 2, and Month 3/Week12. | The survey, IPSS-International Prostate Score Scale, survey responses measured 0-35, is collected at baseline compared to post dose survey response at Month 1, Month 2, and Month 3/Week12 post-dose. The lower the score is indicative of less or fewer urinary symptoms while 35 is consistent with more bothersome symptoms. | Change from baseline to months 1, 2 and 3 | 
| Change in PPUS-Patient Perception of Urinary Urgency Survey Score at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 | The Patient Perception of Urinary Urgency self administered survey score has a maximum score 4, zero to four, for how severe a patient describes their urinary voiding frequency. Four is the most bothersome score, 0 or 1 is the least bothersome. Pre-dose / baseline score is compared at Month 1, Month 2, and Month 3, after dosing with tamsulosin and solifenacin. | Change from baseline to months 1, 2 and 3 | 
| Change in PBC-Patient Perception of Bladder Condition at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 | Change in the Perception of Bladder through a self administered survey at baseline compared to Month 1, Month 2, and Month 3, following exposure to tamsulosin and solifenacin. The survey score measures from zero to 6, with 6 being the most bothersome bladder symptoms and 0 to 1 being the least bothersome. | Change from baseline to months 1, 2 and 3 | 
| Change in ICIQ-MLUTS - International Consultation on Incontinence Modular Questionnaire for Male LUTS Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 | Measuring change in the International Consultation on Incontinence Modular Questionnaire for male lower urinary tract symptoms through a self administered survey at baseline compared to Month 1, Month 2, and Month 3, after exposure to tamsulosin and solifenacin. The survey score is a zero to 182 range with 182 being the most bothersome and zero to one being the least bothersome. | Change from baseline to months 1, 2 and 3 | 
| Change in ICIQ LUTS QoL -International Consultation on Incontinence Modular Questionnaire LUTS Quality of Life for Male LUTS Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 | Change in the International Consultation on Incontinence Modular Questionnaire on lower urinary tract symptoms quality of life survey for men, self administered, compared to Month 1, Month 2, and Month 3, after exposure to tamsulosin and solifenacin. The survey scoring is zero to 182, with 182 being the most bothersome and 0 to 1 being the least bothersome. | Change from baseline to months 1, 2 and 3 | 
| Change in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.1/Wk4 and Mo.2/Wk8 | Urine sample tested for urinary Nerve Growth Factor (uNGF as measured in pg/mL), a small secreted protein in the bladder that supports bladder function regulation, at baseline (pre-dose) compared to Month 1/Week 4 and Month 2/Week 8, post dosing with tamsulosin and solifenacin. | Change from baseline to Mo.1/Wk4 and Mo.2/Wk8 | 
| Change in Urinary Growth Factor to Creatinine Ratio (GF/Cr) From Baseline Compared to Month 1/Week4 and Month 2/Week 8. | Assessing the change from baseline to Month 1/Week 4 and Month 2/Week 8, of the urinary growth factor (GF) to creatinine ratio in men, which may be potential biomarker for overactive bladder, based on published articles. Measuring the ratio at baseline compared to Month 1 and Month 2 may provide insight into how lower urinary tract symptoms in men progresses. | change from baseline score to Mo.1/Wk4 and Mo.2/Wk8 scores |