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

NCT01457573 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: Pro00006253IRB# 0711-0124
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Lower Urinary Tract Symptoms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

One (single arm)

EXPERIMENTAL

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; Drug: Solifenacin

Interventions

Tamsulosin DRUG

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®).

Also known as: tamsulosin hydrochloride, tamsulosin HCl, Flomax®

One (single arm)

Solifenacin DRUG

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

Also known as: solifenacin succinate, VESIcare®, Vesicare®

One (single arm)

Eligibility Criteria

• Age: 45 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Timothy Boone, MD, PhD: lead
• Astellas Pharma US, Inc.: collaborator

Study Sites (1)

The Methodist Hospital System

Houston, Texas, 77030, United States

Location

Related Publications (13)

• McVary KT. 2010 AUA Benign Prostatic Hyperplasia Clinical Guidelines. Panel Chair, AUA News 2010; 15 (3) 10 - 11.

  BACKGROUND

• Chapple CR, Roehrborn CG. A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder. Eur Urol. 2006 Apr;49(4):651-8. doi: 10.1016/j.eururo.2006.02.018. Epub 2006 Feb 17.

  PMID: 16530611 BACKGROUND

• Kaplan SA. New data on Tolterodine: Do recent findings dispel questions about treating overactive bladder in men? Eur Urology 2007; Suppl 6: 10-16.

  BACKGROUND

• Lee JY, Kim HW, Lee SJ, Koh JS, Suh HJ, Chancellor MB. Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder. BJU Int. 2004 Oct;94(6):817-20. doi: 10.1111/j.1464-410X.2004.05039.x.

  PMID: 15476515 BACKGROUND

• Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28. doi: 10.1001/jama.296.19.2319.

  PMID: 17105794 BACKGROUND

• Kaplan SA, Roehrborn CG, Chancellor M, Carlsson M, Bavendam T, Guan Z. Extended-release tolterodine with or without tamsulosin in men with lower urinary tract symptoms and overactive bladder: effects on urinary symptoms assessed by the International Prostate Symptom Score. BJU Int. 2008 Nov;102(9):1133-9. doi: 10.1111/j.1464-410X.2008.07761.x. Epub 2008 May 26.

  PMID: 18510659 BACKGROUND

• Kaplan SA, Goldfischer ER, Steers WD, Gittelman M, Andoh M, Forero-Schwanhaeuser S. Solifenacin treatment in men with overactive bladder: effects on symptoms and patient-reported outcomes. Aging Male. 2010 Jun;13(2):100-7. doi: 10.3109/13685530903440408.

  PMID: 20001469 BACKGROUND

• Liu HT, Kuo HC. Urinary nerve growth factor level could be a potential biomarker for diagnosis of overactive bladder. J Urol. 2008 Jun;179(6):2270-4. doi: 10.1016/j.juro.2008.01.146. Epub 2008 Apr 18.

  PMID: 18423678 BACKGROUND

• Yokoyama T, Kumon H, Nagai A. Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder. Neurourol Urodyn. 2008;27(5):417-20. doi: 10.1002/nau.20519.

  PMID: 17924444 BACKGROUND

• Liu HT, Chancellor MB, Kuo HC. Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder. BJU Int. 2009 Jun;103(12):1668-72. doi: 10.1111/j.1464-410X.2009.08380.x. Epub 2009 Feb 11.

  PMID: 19220267 BACKGROUND

• Jacobs BL, Smaldone MC, Tyagi V, Philips BJ, Jackman SV, Leng WW, Tyagi P. Increased nerve growth factor in neurogenic overactive bladder and interstitial cystitis patients. Can J Urol. 2010 Feb;17(1):4989-94.

  PMID: 20156378 BACKGROUND

• Cardozo L, Hessdorfer E, Milani R, Arano P, Dewilde L, Slack M, Drogendijk T, Wright M, Bolodeoku J; SUNRISE Study Group. Solifenacin in the treatment of urgency and other symptoms of overactive bladder: results from a randomized, double-blind, placebo-controlled, rising-dose trial. BJU Int. 2008 Nov;102(9):1120-7. doi: 10.1111/j.1464-410X.2008.07939.x. Epub 2008 Oct 6.

  PMID: 18990175 BACKGROUND

• Dmochowski RR, Gomelsky A. Overactive bladder in males. Ther Adv Urol. 2009 Oct;1(4):209-21. doi: 10.1177/1756287209350383.

  PMID: 21789068 RESULT

MeSH Terms

Conditions

Lower Urinary Tract Symptoms

Interventions

Tamsulosin; Solifenacin Succinate

Condition Hierarchy (Ancestors)

Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Timothy Boone, MD, PhD, Principal Investigator
• Organization: Houston Methodist Hosptial System

tboone3@houstonmethodist.org

713-441-6455

Study Officials

• Timothy Boone, MD,PhD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator/Principal Investigator

Study Record Dates

• First Submitted: October 20, 2011
• First Posted: October 24, 2011
• Study Start: October 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: April 2, 2018
• Results First Posted: April 2, 2018

Record last verified: 2018-03

Locations

US (1)