ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01457573
Recruitment Status : Completed
First Posted : October 24, 2011
Results First Posted : April 2, 2018
Last Update Posted : April 2, 2018
Sponsor:
Collaborator:
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Timothy Boone, MD, PhD, The Methodist Hospital System

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.

Condition or disease Intervention/treatment Phase
Lower Urinary Tract Symptoms Drug: Tamsulosin Drug: Solifenacin Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Urinary Nerve Growth Factor as a Biomarker for Medical Treatment of Male Lower Urinary Tract Symptoms: A Pilot Trial
Actual Study Start Date : October 2011
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: One (single arm)
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
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®).
Other Name: tamsulosin hydrochloride, tamsulosin HCl, Flomax®
Drug: Solifenacin
Antispasmodic/anticholinergic used to treat overactive bladder. All men will receive Solifenacin (Vesicare®) 5 mg, 1 tab, per morning with Tamsulosin.
Other Name: solifenacin succinate, VESIcare®, Vesicare®



Primary Outcome Measures :
  1. Change in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.3/Wk12 [ Time Frame: 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.

  2. Change From Baseline in Urinary Growth Factor to Creatinine Ratio (GF/Cr) [ Time Frame: 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 Outcome Measures :
  1. Change in Post Void Residual (mL) at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 [ Time Frame: 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.

  2. Change in Maximum Urinary Flow Rate (ml/s) at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 [ Time Frame: 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.

  3. Change in IPSS-International Prostate Score Scale at Baseline Compared to Post Dose Survey at Month 1, 2, and Month 3/Week12. [ Time Frame: 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.

  4. 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 [ Time Frame: 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.

  5. Change in PBC-Patient Perception of Bladder Condition at Baseline Compared to Post Dose Exposure at Mo.1, Mo, 2, and Mo. 3/Wk12 [ Time Frame: 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.

  6. 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 [ Time Frame: 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.

  7. 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 [ Time Frame: 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.

  8. Change in Urinary Nerve Growth Factor (pg/mL) at Baseline Compared to Post Dose Exposure at Mo.1/Wk4 and Mo.2/Wk8 [ Time Frame: 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.

  9. Change in Urinary Growth Factor to Creatinine Ratio (GF/Cr) From Baseline Compared to Month 1/Week4 and Month 2/Week 8. [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01457573


Locations
United States, Texas
The Methodist Hospital System
Houston, Texas, United States, 77030
Sponsors and Collaborators
Timothy Boone, MD, PhD
Astellas Pharma US, Inc.
Investigators
Principal Investigator: Timothy Boone, MD,PhD The Methodist Hospital System

Publications of Results:
Other Publications:
McVary KT. 2010 AUA Benign Prostatic Hyperplasia Clinical Guidelines. Panel Chair, AUA News 2010; 15 (3) 10 - 11.
Kaplan SA. New data on Tolterodine: Do recent findings dispel questions about treating overactive bladder in men? Eur Urology 2007; Suppl 6: 10-16.

Responsible Party: Timothy Boone, MD, PhD, Sponsor-Investigator/Principal Investigator, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT01457573     History of Changes
Other Study ID Numbers: Pro00006253
IRB# 0711-0124 ( Other Identifier: HMRI IRB )
First Posted: October 24, 2011    Key Record Dates
Results First Posted: April 2, 2018
Last Update Posted: April 2, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Plan to share data to be determined.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Mitogens
Tamsulosin
Solifenacin Succinate
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Urological Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents