Ignite Creation Date:
2025-12-25 @ 2:06 AM
Ignite Modification Date:
2025-12-26 @ 2:05 AM
Study NCT ID:
NCT04626960
Status:
COMPLETED
Last Update Posted:
2020-11-13
First Post:
2020-11-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
ADRB3, ROCK2 and GEF Levels in Overactive Bladder Patients
Sponsor:
Pamukkale University
Organization:
Study Overview
Official Title:
ADRB3, ROCK2 and GEF Levels in Overactive Bladder Patients
Status:
COMPLETED
Status Verified Date:
2020-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Aims: To evaluate changes in levels of ADRB3, ROCK2, and GEF which have key roles in the adrenergic and cholinergic pathways of contraction-relaxation harmony in voiding physiology, and to investigate the diagnostic potential of these proteins in OAB.
Methods: This study included 60 idiopathic OAB patients and a healthy control group. All patients completed a validated OAB-V8 questionnaire. Serum levels of ADRB3, ROCK2, and GEF were examined by ELISA. ROC curves were generated to evaluate the diagnostic performance of these protein levels for OAB diagnosis.
Methods: This study included 60 idiopathic OAB patients and a healthy control group. All patients completed a validated OAB-V8 questionnaire. Serum levels of ADRB3, ROCK2, and GEF were examined by ELISA. ROC curves were generated to evaluate the diagnostic performance of these protein levels for OAB diagnosis.
Detailed Description:
Overactive bladder (OAB) is defined by The Standardization Subcommittee of the International Continence Society (ICS) as a symptom syndrome consisting of urgency, with or without urge incontinence, usually with frequency and nocturia, in the absence of proven infection or other obvious pathology. OAB is a clinical diagnosis and its assessment is very important, especially for evaluation of treatment effectiveness. OAB is diagnosed by symptoms only, and symptoms are subjective definitions that vary from person to person. Therefore, various scoring systems and urodynamic tests are used to make an objective diagnosis and to determine the severity of symptoms. In recent studies, there are several substances that have been proposed as biomarkers of OAB, such as especially urinary proteins but studies that have compared these markers are lacking, also these proteins present low sensitivity and specificity. In the future, physicians may consider the use of biomarkers to identify distinct OAB phenotypes, with distinct causal mechanisms, selecting patients for specific target therapies with expected better outcomes. Biomarkers can be useful to phenotype patients and for selecting more effective target therapies. So, there is a need for stable and non-invasive biomarkers that can be used reliably for assessment of OAB.
Even though the exact cause or causes of OAB have not yet been identified, the most powerful theory accepted in pathogenesis is detrusor muscle hyperactivity by relaxation decrease or contractions increase in detrusor smooth muscle. The molecular mechanisms underlying the OAB clinic are still not fully understood.
Bladder contractions are primarily controlled by parasympathetic cholinergic pathways. Guanine nucleotide exchange factors (GEF) and Rho-related kinase (ROCK) are important in this way. ROCKs are also important regulators of cellular apoptosis, growth, metabolism, and migration through control of the cell contraction. GEFs activate small GTPases and they are regulatory factors that facilitate the separation of GDP from Rho and the binding of GTP. GEF protein regulates Rho activity. Overexpression of GEF leads to an increase in GTP-dependent Rho. GTP-dependent Rho enables ROCK2 activation. ROCK2 especially has an important role in regulating smooth muscle contraction. So, functional disorder or alteration in levels of GEF and ROCK2 can cause an excessive contraction in smooth muscle and may be effective in the basis of pathophysiology in OAB.
The relaxation of the bladder smooth muscle is controlled by a sympathetic cholinergic pathway in which adrenergic receptor β3 (ADRB3) plays a major role. They have an important role in regulating smooth muscle tone, especially in the bladder, and show their effect in many tissues, such as adipose tissue, through relaxation or thermogenesis. The hypofunction of this receptor causes disruption of the bladder detrusor muscle and dysfunction of the urinary tract. So a decrease in ADRB3 levels may be responsible for reduced relaxation in the pathophysiology of overactive bladder.
The aim of this study was to understand whether ADRB3, ROCK2, and GEF levels could be auxiliary parameters for the evaluation of the molecular mechanisms of OAB and to diagnose. If changes in levels of these parameters affect the amounts and functions of proteins in these pathways, the pathogenesis of OAB can be better understood and new treatment goals can be recommended.
Even though the exact cause or causes of OAB have not yet been identified, the most powerful theory accepted in pathogenesis is detrusor muscle hyperactivity by relaxation decrease or contractions increase in detrusor smooth muscle. The molecular mechanisms underlying the OAB clinic are still not fully understood.
Bladder contractions are primarily controlled by parasympathetic cholinergic pathways. Guanine nucleotide exchange factors (GEF) and Rho-related kinase (ROCK) are important in this way. ROCKs are also important regulators of cellular apoptosis, growth, metabolism, and migration through control of the cell contraction. GEFs activate small GTPases and they are regulatory factors that facilitate the separation of GDP from Rho and the binding of GTP. GEF protein regulates Rho activity. Overexpression of GEF leads to an increase in GTP-dependent Rho. GTP-dependent Rho enables ROCK2 activation. ROCK2 especially has an important role in regulating smooth muscle contraction. So, functional disorder or alteration in levels of GEF and ROCK2 can cause an excessive contraction in smooth muscle and may be effective in the basis of pathophysiology in OAB.
The relaxation of the bladder smooth muscle is controlled by a sympathetic cholinergic pathway in which adrenergic receptor β3 (ADRB3) plays a major role. They have an important role in regulating smooth muscle tone, especially in the bladder, and show their effect in many tissues, such as adipose tissue, through relaxation or thermogenesis. The hypofunction of this receptor causes disruption of the bladder detrusor muscle and dysfunction of the urinary tract. So a decrease in ADRB3 levels may be responsible for reduced relaxation in the pathophysiology of overactive bladder.
The aim of this study was to understand whether ADRB3, ROCK2, and GEF levels could be auxiliary parameters for the evaluation of the molecular mechanisms of OAB and to diagnose. If changes in levels of these parameters affect the amounts and functions of proteins in these pathways, the pathogenesis of OAB can be better understood and new treatment goals can be recommended.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: