ADRB3, ROCK2 and GEF Levels in Overactive Bladder Patients

NCT ID: NCT04626960

Last Updated: 2020-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-06-05

Study Completion Date

2020-06-07

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Overactive Bladder

Keywords

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ADRB3; Biomarkers; GEF; Overactive bladder; ROCK2.

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Patient

OAB patients

No interventions assigned to this group

Control

Healthy

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Clinical diagnosis of Idiopathic Overactive Bladder
* Must have at least 11 points on the OAB-V8 questionnaire

Exclusion Criteria

* Neurogenic bladder
* Bladder obstruction
* Urinary tract diseases such as stones, tumors, infections
* Long QT syndrome
* Severe liver failure
* Renal failure
* Myasthenia
* Glaucoma
* Autoimmune disease
* Lower urinary tract dysfunction
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Pamukkale University

OTHER

Sponsor Role lead

Responsible Party

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Elif Fırat

Principal Investigator, Medical Biochemistry Specialist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elif Fırat

Role: PRINCIPAL_INVESTIGATOR

[email protected]

Hülya Aybek

Role: STUDY_CHAIR

[email protected]

Zafer Aybek

Role: STUDY_DIRECTOR

[email protected]

Locations

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Pamukkale University

Denizli, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21(2):167-78. doi: 10.1002/nau.10052. No abstract available.

Reference Type BACKGROUND
PMID: 11857671 (View on PubMed)

Meng E, Lin WY, Lee WC, Chuang YC. Pathophysiology of Overactive Bladder. Low Urin Tract Symptoms. 2012 Mar;4 Suppl 1:48-55. doi: 10.1111/j.1757-5672.2011.00122.x.

Reference Type BACKGROUND
PMID: 26676700 (View on PubMed)

Antunes-Lopes T, Cruz F. Urinary Biomarkers in Overactive Bladder: Revisiting the Evidence in 2019. Eur Urol Focus. 2019 May;5(3):329-336. doi: 10.1016/j.euf.2019.06.006. Epub 2019 Jun 21.

Reference Type BACKGROUND
PMID: 31231010 (View on PubMed)

Other Identifiers

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2019HZDP009

Identifier Type: -

Identifier Source: org_study_id