Association of Urine BDNF and NGF With Lower Urinary System Parameters

Lower Urinary Tract Obstructive Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06265519
• Other study ID #: MAR.UAD.008
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2024
• Est. completion date: July 1, 2025

Study information

• Verified date: February 2024
• Source: Marmara University
• Contact: Haydar Kamil ÇAM, Prof. Dr.
• Phone: +905323259547
• Email: kamilcam[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: July 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperplasia
• Lower Urinary Tract Obstructive Syndrome
• Prostatic Hyperplasia

Intervention

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

Locations

Country	Name	City	State
Turkey	Marmara University Hospital	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Marmara University

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	International prostate symptom score	International prostate symptom score	1 year