Urinary NGF as A Biomarker for Acute Bacterial Cystitis

NCT01800799 | Completed

• 1 other identifier: TCGHUROL007
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll 30 female patients with the first time urinary tract infection (UTI), 30 female patients with recurrent UTI and 10 female without any prior history of UTI or urinary tract pathology will be invited to serve as the controls. Urine samples will be collected in the patients at baseline, 7 days after antibiotics treatment, and 2 weeks, 4 weeks, 8 weeks, and 12 weeks. Urinalysis will be performed at each visit and urine culture will be performed at baseline and at the 2 weeks and 3 months visits. Urine samples at baseline and 3 months will be collected from the controls for comparison.

Conditions

Urinary Tract Infection

Keywords

Urinary tract infection; Urothelium; Inflammation; Apoptosis

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in urinary nerve growth factor (NGF) at different time points

  Change from Baseline in urinary nerve growth factor (NGF) at different time points (1 week, 1 month, 2 months and 3 months).

  1 week, 1 month, 2 months and 3 months

Secondary Outcomes (3)

• Change from Baseline in one-day voiding diary at different time points

  1 week, 1 month, 2 months and 3 months

• Change from Baseline in Overactive Bladder Symptom Score (OABSS) at different time points

  1 week, 1 month, 2 months and 3 months

• Change from Baseline in visual analog scale of pain (VAS) at different time points

  1 week, 1 month, 2 months and 3 months

Study Arms (3)

UTI (WBC>10 per high power field)

EXPERIMENTAL

1. Antimicrobial agent (Baktar 800mg h.s.) 2. Anti-inflammatory agent (Celecoxib 200mg QD)

Drug: Baktar 800mg h.s.; Drug: Celecoxib 200mg QD

Recurrent UTI

EXPERIMENTAL

1. Antimicrobial agent (Baktar 800mg h.s.) 2. Anti-inflammatory agent (Celecoxib 200mg QD)

Drug: Baktar 800mg h.s.; Drug: Celecoxib 200mg QD

Normal control

NO INTERVENTION

Normal control

Interventions

Baktar 800mg h.s. DRUG

Antimicrobial agent (Baktar 800mg h.s.)

Also known as: Antimicrobial agent

Recurrent UTI; UTI (WBC>10 per high power field)

Celecoxib 200mg QD DRUG

Anti-inflammatory agent (Celecoxib 200mg QD)

Also known as: Anti-inflammatory agent

Recurrent UTI; UTI (WBC>10 per high power field)

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female adults aged ≥ 20 years.
• All patients should be proven to have UTI by detecting pyuria in urinalysis (WBC\>10 per high power field) and had a positive urine culture result.
• A KUB film, and renal sonography will be performed to exclude to possibility of urolithiasis or other urinary tract pathology.
• Not yet have lower urinary tract surgery in the past.
• The patient has not yet accepted anticholinergic medication
• Patient or his legally acceptable representative has signed the written informed consent form.

You may not qualify if:

• Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up.
• Patients with uncontrolled confirmed diagnosis of acute urinary tract infection.
• Patients have laboratory abnormalities at screening including: (1) Aspartate aminotransferase (AST) \> 3 x upper limit of normal range. (2) Alanine aminotransferase (ALT) \> 3 x upper limit of normal range. (3) Patients have abnormal serum creatinine level \> 2 x upper limit of normal range.
• Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
• Patients with any other serious disease or condition considered by the investigator not suitable for entry into the trial.
• Patients participated investigational drug trial within 1 month before entering this study.
• Patient or his legally written informed consent hadn't been obtained.

Sponsors & Collaborators

• Buddhist Tzu Chi General Hospital: lead

Study Sites (1)

Buddhist Tzu Chi General Hospital

Hualien City, 970, Taiwan

Location

Related Publications (18)

• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. doi: 10.1002/nau.20798.

  PMID: 19941278 BACKGROUND

• Liu HT, Chen CY, Kuo HC. Urinary nerve growth factor levels in overactive bladder syndrome and lower urinary tract disorders. J Formos Med Assoc. 2010 Dec;109(12):862-78. doi: 10.1016/S0929-6646(10)60133-7.

  PMID: 21195884 BACKGROUND

• Vizzard MA. Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp Neurol. 2000 Jan;161(1):273-84. doi: 10.1006/exnr.1999.7254.

  PMID: 10683293 BACKGROUND

• Yoshimura N. Bladder afferent pathway and spinal cord injury: possible mechanisms inducing hyperreflexia of the urinary bladder. Prog Neurobiol. 1999 Apr;57(6):583-606. doi: 10.1016/s0301-0082(98)00070-7.

  PMID: 10221783 BACKGROUND

• Vizzard MA. Neurochemical plasticity and the role of neurotrophic factors in bladder reflex pathways after spinal cord injury. Prog Brain Res. 2006;152:97-115. doi: 10.1016/S0079-6123(05)52007-7.

  PMID: 16198696 BACKGROUND

• Seki S, Sasaki K, Igawa Y et al. Detrusor overactivity induced by increased levels of nerve growth factor in bladder afferent pathways in rats. Neurourol Urodyn 2003; 22: 375-7

  BACKGROUND

• Lamb K, Gebhart GF, Bielefeldt K. Increased nerve growth factor expression triggers bladder overactivity. J Pain. 2004 Apr;5(3):150-6. doi: 10.1016/j.jpain.2004.01.001.

  PMID: 15106127 BACKGROUND

• Yoshimura N, Bennett NE, Hayashi Y, Ogawa T, Nishizawa O, Chancellor MB, de Groat WC, Seki S. Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats. J Neurosci. 2006 Oct 18;26(42):10847-55. doi: 10.1523/JNEUROSCI.3023-06.2006.

  PMID: 17050722 BACKGROUND

• Zvara P, Vizzard MA. Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord. BMC Physiol. 2007 Aug 28;7:9. doi: 10.1186/1472-6793-7-9.

  PMID: 17725832 BACKGROUND

• Liu HT, Kuo HC. Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology. 2008 Jul;72(1):104-8; discussion 108. doi: 10.1016/j.urology.2008.01.069. Epub 2008 Apr 8.

  PMID: 18400272 BACKGROUND

• Lowe EM, Anand P, Terenghi G, Williams-Chestnut RE, Sinicropi DV, Osborne JL. Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol. 1997 Apr;79(4):572-7. doi: 10.1046/j.1464-410x.1997.00097.x.

  PMID: 9126085 BACKGROUND

• Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007 Sep;70(3):463-8. doi: 10.1016/j.urology.2007.04.038.

  PMID: 17905097 BACKGROUND

• Kim JC, Park EY, Seo SI, Park YH, Hwang TK. Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol. 2006 May;175(5):1773-6; discussion 1776. doi: 10.1016/S0022-5347(05)00992-4.

  PMID: 16600756 BACKGROUND

• Liu HT, Chancellor MB, Kuo HC. Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection. Eur Urol. 2009 Oct;56(4):700-6. doi: 10.1016/j.eururo.2008.04.037. Epub 2008 Apr 30.

  PMID: 18472208 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

• Liu HT, Kuo HC. Urinary nerve growth factor levels are elevated in patients with overactive bladder and do not significantly increase with bladder distention. Neurourol Urodyn. 2009;28(1):78-81. doi: 10.1002/nau.20599.

  PMID: 19089891 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

• Kuo HC, Liu HT, Tyagi P, Chancellor MB. Urinary Nerve Growth Factor Levels in Urinary Tract Diseases With or Without Frequency Urgency Symptoms. Low Urin Tract Symptoms. 2010 Sep;2(2):88-94. doi: 10.1111/j.1757-5672.2010.00065.x. Epub 2010 May 3.

  PMID: 26676289 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections; Inflammation

Interventions

Anti-Infective Agents; Celecoxib; Anti-Inflammatory Agents

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hann-Chorng Kuo, M.D.

  Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Urology

Study Record Dates

• First Submitted: February 19, 2013
• First Posted: February 28, 2013
• Study Start: February 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 17, 2017

Record last verified: 2017-02

Locations

TW (1)