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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01457573

Acronym

LUTS

Enrollment

Registered

2011-10-24

Start date

2011-10-31

Completion date

2014-07-31

Last updated

2018-04-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lower Urinary Tract Symptoms

Brief summary

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

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.

Interventions

DRUGTamsulosin

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®).

DRUGSolifenacin

Antispasmodic/anticholinergic used to treat overactive bladder. All men will receive Solifenacin (Vesicare®) 5 mg, 1 tab, per morning with Tamsulosin.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

45 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Change in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.3/Wk12	Change from baseline to week 12 (3 months)	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 in Urinary Growth Factor to Creatinine Ratio (GF/Cr)	change from baseline score to Month 3	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.

Secondary

Measure	Time frame	Description
Change in IPSS-International Prostate Score Scale at Baseline Compared to Post Dose Survey at Month 1, 2, and Month 3/Week12.	Change from baseline to months 1, 2 and 3	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 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	Change from baseline to months 1, 2 and 3	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 in PBC-Patient Perception of Bladder Condition at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12	Change from baseline to months 1, 2 and 3	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 in Maximum Urinary Flow Rate (ml/s) at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12	Change from baseline to months 1, 2 and 3	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 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 from baseline to months 1, 2 and 3	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 in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.1/Wk4 and Mo.2/Wk8	Change from baseline to 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 in Urinary Growth Factor to Creatinine Ratio (GF/Cr) From Baseline Compared to Month 1/Week4 and Month 2/Week 8.	change from baseline score to Mo.1/Wk4 and Mo.2/Wk8 scores	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 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	Change from baseline to months 1, 2 and 3	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 in Post Void Residual (mL) at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12	Change from baseline to months 1, 2 and 3	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.

Countries

United States

Participant flow

Recruitment details

Potential participants were approached by the PI and Study Team in an outpatient urology clinic setting between October 2011 and December 2014 for recruitment to the male lower urinary tract symptoms study.

Participants by arm

Arm	Count
All Study Participants Men \> 50 years old with urinary frequency symptoms, who entered study not taking any bladder related medications and on study took tamsulosin and solifenacin orally everyday throughout the study with follow-up assessments at Month 1/week 4, Month 2 week 8, and Month 3/week 12.	10
Total	10

Baseline characteristics

Characteristic	All Study Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	8 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Age, Continuous	64 years
Baseline International Consultation on Incontinence Mod. Questions Lower Urinary Tract Symptoms QoL	122.6 units on a scale STANDARD_DEVIATION 59.53
Baseline International Consultation on Incontinence Mod. Questions-Male Lower Urinary Tract Symptoms	67.2 units on a scale STANDARD_DEVIATION 21.04
Baseline International Prostate Symptom Score (IPSS)	18.2 units on a scale STANDARD_DEVIATION 5.07
Baseline Maximum urinary flow rate	18.71 ml/s STANDARD_DEVIATION 9.27
Baseline Patient Perception of Urgency Score (PPUS)	2.5 units on a scale STANDARD_DEVIATION 0.85
Baseline Perception of Bladder Condition (PBC)	3.5 units on a scale STANDARD_DEVIATION 0.85
Baseline Post-void residual (PVR) of urine	53.89 ml STANDARD_DEVIATION 51.74
Baseline Urinary Nerve Growth Factor	37.10 pg/ml STANDARD_DEVIATION 21.24
Baseline Urinary Nerve Growth Factor (pg/ml)/Cr (mg/dl)	34.20 ratio STANDARD_DEVIATION 56.69
Region of Enrollment United States	10 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	10 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	1 / 10
serious Total, serious adverse events	0 / 10

Outcome results

Primary

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.

Time frame: change from baseline score to Month 3

Arm	Measure	Value (MEAN)	Dispersion
Single Arm Receiving Tamsulosin 0.4 mg and Solifenacin 5 mg	Change From Baseline in Urinary Growth Factor to Creatinine Ratio (GF/Cr)	-19.61 ratio	Standard Deviation 13.21

Primary

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.

Time frame: Change from baseline to week 12 (3 months)

Arm	Measure	Value (MEAN)	Dispersion
Single Arm Receiving Tamsulosin 0.4 mg and Solifenacin 5 mg	Change in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.3/Wk12	-10.9 pg/ml	Standard Deviation 22.81

Secondary

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.