Association of Urine BDNF and NGF With Lower Urinary System Parameters

The Association of Urinary BDNF and NGF With Lower Urinary System Parameters in Patients With Bladder Outlet Obstruction Secondary to Benign Prostate Hyperplasia

Histologically, BPH is a benign proliferative process involving both epithelial and stromal elements and is characterised by progressive enlargement of the prostate. Symptom complex including increased frequency of urination, sudden feeling of urge to urinate, nocturia, difficulty in urinating, feeling of incomplete emptying of the bladder, decreased flow rate and intermittent urination are called lower urinary tract symptoms (LUTS). The most important cause of LUTS in men is BPH. Many structural and physiological changes occur in the lower urinary system with bladder outlet obstruction. Detrusor hypertrophy and bladder hyperactivity may occur due to bladder outlet obstruction. Although the density of afferent and efferent nerves in the bladder decreases after urethral obstruction, enlargement of their trunks indicates that changes occur in these nerves. In addition, changes also occur in the neural pathways of the central nervous system following lower urinary tract obstruction. Nerve growth factor (NGF) and brain derived neurotropin factor (BDNF) are trophic proteins that act as retrograde messengers between peripheral effector tissue and the nerves that innervate it. In peripheral tissues, the source of NGF and BDNF is presumed to be the target tissues innervated by nerves. Smooth muscle cells, fibroblasts, astrocytes and other cells synthesise NGF and BDNF in culture medium. Many potential stimuli that increase NGF in the lower urinary system have been identified. These are denervation, inflammation and mechanical tension. This information has led to the idea that autonomic innervation changes in the bladder may be related with changing NGF levels. Altered afferent and adrenergic innervation in the obstructed bladder increases the possibility that NGF plays an important role in this neural growth because this type of nerves are highly sensitive to this neurotrophin.

In this study, we investigated NGF ve BDNF levels in urine samples obtained before surgery (Transurethral Prostate Resection, Prostate Enucleation with Holmium Laser and Prostate Enucleation with Thulium Fibre Laser) and after removal of obstruction in patients with bladder outlet obstruction secondary to benign prostatic enlargement using ELISA method, We aimed to determine the role of NGF and BDNF in bladder outlet obstruction and bladder changes secondary to obstruction by comparing with control patients without obstruction.

Study Overview

• Status: Recruiting
• Conditions: Lower Urinary Tract Obstructive Syndrome; Benign Prostatic Hyperplasia With Outflow Obstruction
• Intervention / Treatment: Procedure: Holmium laser enucleation of the prostate

Detailed Description

As the demographic structure of societies changes, benign prostatic hyperplasia (BPH) is one of the most important health problems for older men, especially in developed countries. Histologically, BPH is a benign proliferative process involving both epithelial and stromal elements and is characterised by progressive enlargement of the prostate. BPH is a lifelong chronic disease with an incidence of approximately 8% in men aged 31-40 years, which increases rapidly with age and reaches 90% in the 9th decade. Symptom complex including increased frequency of urination, sudden feeling of urge to urinate, nocturia, difficulty in urinating, feeling of incomplete emptying of the bladder, decreased flow rate and intermittent urination are called lower urinary tract symptoms (LUTS). The most important cause of LUTS in men is BPH. Many structural and physiological changes occur in the lower urinary system with bladder outlet obstruction. Detrusor hypertrophy and bladder hyperactivity may occur due to bladder outlet obstruction. Although the density of afferent and efferent nerves in the bladder decreases after urethral obstruction, enlargement of their trunks indicates that changes occur in these nerves.

In addition, changes also occur in the neural pathways of the central nervous system following lower urinary tract obstruction. Nerve growth factor (NGF) and brain derived neurotropin factor (BDNF) are trophic proteins that act as retrograde messengers between peripheral effector tissue and the nerves that innervate it. In peripheral tissues, the source of NGF and BDNF is presumed to be the target tissues innervated by nerves. Smooth muscle cells, fibroblasts, astrocytes and other cells synthesise NGF and BDNF in culture medium. NGF is required for survival, development and neurotransmitter synthesis regulation of dorsal root ganglion and sympathetic cells in embryonic and postnatal life . NGF receptor contains two subunits; the low affinity subunit is called p75 and the high affinity tyrosine kinase subunit is called tyrosine kinase A which is responsible for the growth and survival effects of NGF. Many potential stimuli that increase NGF in the lower urinary system have been identified. These are denervation, inflammation and mechanical tension. This information has led to the idea that autonomic innervation changes in the bladder may be related with changing NGF levels. Altered afferent and adrenergic innervation in the obstructed bladder increases the possibility that NGF plays an important role in this neural growth because this type of nerves are highly sensitive to this neurotrophin. Clinical and experimental data have shown a relationship between urinary NGF and overactive bladder. Overactive bladder (OAB) is a complex of uncomfortable symptoms accompanied by a feeling of urgency, frequent urination and nocturia, with or without urge incontinence. Overactive bladder is thought to occur as a result of an inflammatory process occurring in the bladder. The reason for this is shown as high levels of inflammation mediators in bladder biopsies and urine of OAB patients. NGF, which is one of the inflammation mediators, was found to be high in OAB patients in studies and it was observed that NGF level decreased after antimuscarinic treatment or botulinum neurotoxin injection.

In this study, we investigated NGF ve BDNF levels in urine samples obtained before surgery (Transurethral Prostate Resection, Prostate Enucleation with Holmium Laser and Prostate Enucleation with Thulium Fibre Laser) and after removal of obstruction in patients with bladder outlet obstruction secondary to benign prostatic enlargement using ELISA method, We aimed to determine the role of NGF and BDNF in bladder outlet obstruction and bladder changes secondary to obstruction by comparing with control patients without obstruction.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kader Ada Doğan, MD; Phone Number: +905323845598; Email: kader.dogan11@gmail.com
• Study Contact Backup: Name: Haydar Kamil ÇAM, Prof. Dr.; Phone Number: +905323259547; Email: kamilcam@hotmail.com

Study Locations

• Turkey
  • Istanbul, Turkey
    • Recruiting
    • Marmara University Hospital
    • Contact: Haydar Kamil Çam, Prof.; Phone Number: +905323259547; Email: kamilcam@hotmail.com
    • Contact: Kader Ada Doğan, MD; Phone Number: +905323845598; Email: kader.dogan11@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 50-80 years Male
2. Patients with bladder outlet obstruction secondary to benign prostate hyperplasia

Exclusion Criteria:

1. Known neurological disease
2. Diabetes
3. Urinary tract infection
4. Previous prostate surgery
5. Spinal Cord Trauma

7-Bladder stone 8-Cerebrovascular disease 9-Chronic Renal Failure 10-Ureteral stenosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients before surgery; Men between the ages of 50 and 80 diagnosed with BPH before surgery	Procedure: Holmium laser enucleation of the prostate; Holmium laser enucleation of the prostate is a minimally invasive procedure that uses pulses of laser beam to remove tissue from the inside of the prostate, which surrounds the urethra (the tube leading from the bladder to the urinary opening) in patients with BPH
Active Comparator: Patients after surgery; Men between the ages of 50 and 80 diagnosed with BPH after surgery	Procedure: Holmium laser enucleation of the prostate; Holmium laser enucleation of the prostate is a minimally invasive procedure that uses pulses of laser beam to remove tissue from the inside of the prostate, which surrounds the urethra (the tube leading from the bladder to the urinary opening) in patients with BPH
No Intervention: Healthy; Men between the ages of 50-80 years without lower urinary tract disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uroflowmetry	Uroflowmetry is a test that measures the volume of urine released from the body, the speed with which it is released, and how long the release takes.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International prostate symptom score	International prostate symptom score	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urodynamic	Urodynamic testing is any procedure that looks at how well parts of the lower urinary tract-the bladder, sphincters, and urethra-work to store and release urine.	Before surgery

Collaborators and Investigators

• Sponsor: Marmara University
• Investigators: Study Director: Tufan Tarcan, Prof. Dr., Marmara University; Study Director: Çağrı Akın Şekerci, Assoc. Prof., Marmara University; Study Director: Banu İşbilen Başok, Prof. Dr., Dr. Behcet Uz Children's Hospital; Study Director: Kader Ada Doğan, MD, Marmara University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Hyperplasia; Hyperplasia
• Other Study ID Numbers: MAR.UAD.008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No