Effect of beta3-adrenoceptor Agonist on Patients With Overactive Bladder and as a Urinary Biomarker

Overactive Bladder Syndrome Clinical Trial

Official title:

To Explore the Effect of beta3-adrenoceptor Agonist on Patients With Overactive Bladder and Develop Its Urinary Biomarker

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04693897
• Other study ID #: CMRPG3K2051
• Status: Not yet recruiting
• Start date: March 1, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2021
• Source: Chang Gung Memorial Hospital
• Contact: Ching-Chung Liang, MD
• Phone: +886-3-3281200
• Email: ccjoliang[@]cgmh.org.tw
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

About one to two million women in Taiwan suffers from overactive bladder (OAB). The most commonly used anti-muscarinic drugs have a high rate of side effects. While beta-3 adrenoceptor agonist, Mirabegron, has far fewer side effects, there are no consensus on whether it can be used as first-line treatment. The investigator's preliminary study showed that the concentration of beta-3 adrenoceptor in the urine of OAB patients is higher than that in the normal control group, so comparing urinary beta-3 adrenoceptor concentration of OAB patients before and after treatment may be used as a biomarker of therapeutic effectiveness. The results of this study will be of great help in understanding the effectiveness of Mirabegron and formulating OAB treatment plans.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis compatible with 2002 ICS for overactive bladder syndrome
• Symptoms persisted for more than 3 months
• Completed pre-treatment urodynamic study
• Has plans for treatment with Mirabegron or Solifenacin due to clinical symptoms
• Patient is willing to cooperate with study including follow up and complete questionnaire surveys

Exclusion Criteria:

• Has stress urinary incontinence
• Pelvic organ prolapse
• Interstitial cystitis
• Constipation
• Gastroesophageal reflux disease
• Prior failed medical treatment for overactive bladder syndrome
• Uncontrolled hypertension
• Glaucoma
• Currently pregnant
• Using other medications for overactive bladder syndrome

Related Conditions & MeSH terms

• Detrusor Overactivity
• Overactive Bladder Syndrome
• Urinary Bladder, Overactive

Intervention

Drug:
• Mirabegron 50 MG
Mirabegron 50mg once daily given to treatment in patients with overactive bladder syndrome
• Solifenacin Succinate 5 MG
Solifenacin 5mg once daily given to treatment in patients with overactive bladder syndrome

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

References & Publications (43)

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Giarenis I, Mastoroudes H, Srikrishna S, Robinson D, Cardozo L. Is there a difference between women with or without detrusor overactivity complaining of symptoms of overactive bladder? BJU Int. 2013 Aug;112(4):501-7. doi: 10.1111/j.1464-410X.2012.11652.x. — View Citation

Hashim H, Abrams P. Is the bladder a reliable witness for predicting detrusor overactivity? J Urol. 2006 Jan;175(1):191-4; discussion 194-5. — View Citation

Hsiao SM, Chang TC, Wu WY, Chen CH, Yu HJ, Lin HH. Comparisons of urodynamic effects, therapeutic efficacy and safety of solifenacin versus tolterodine for female overactive bladder syndrome. J Obstet Gynaecol Res. 2011 Aug;37(8):1084-91. doi: 10.1111/j.1 — View Citation

Hung MJ, Ho ES, Shen PS, Sun MJ, Lin AT, Chen GD; Taiwan OAB Club. Urgency is the core symptom of female overactive bladder syndrome, as demonstrated by a statistical analysis. J Urol. 2006 Aug;176(2):636-40. — View Citation

Igawa Y, Yamazaki Y, Takeda H, Hayakawa K, Akahane M, Ajisawa Y, Yoneyama T, Nishizawa O, Andersson KE. Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle. Br J Pharmacol. 1999 Feb;126(3):819-25. — View Citation

Jafarabadi M, Jafarabadi L, Shariat M, Rabie Salehi G, Haghollahi F, Rashidi BH. Considering the prominent complaint as a guide in medical therapy for overactive bladder syndrome in women over 45 years. J Obstet Gynaecol Res. 2015 Jan;41(1):120-6. doi: 10 — View Citation

Jeong SJ, Lee SC, Jeong CW, Hong SK, Byun SS, Lee SE. Clinical and urodynamic differences among women with overactive bladder according to the presence of detrusor overactivity. Int Urogynecol J. 2013 Feb;24(2):255-61. doi: 10.1007/s00192-012-1817-9. Epub — View Citation

Kuo HC, Lee KS, Na Y, Sood R, Nakaji S, Kubota Y, Kuroishi K. Results of a randomized, double-blind, parallel-group, placebo- and active-controlled, multicenter study of mirabegron, a ß3-adrenoceptor agonist, in patients with overactive bladder in Asia. N — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Luo D, Liu L, Han P, Wei Q, Shen H. Solifenacin for overactive bladder: a systematic review and meta-analysis. Int Urogynecol J. 2012 Aug;23(8):983-91. doi: 10.1007/s00192-011-1641-7. Epub 2012 Feb 7. Review. — View Citation

Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith EJ. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev. 2012 Jan 18;1:CD005429. doi: 10.1002/14651858.CD005429.pub2. Review. — View Citation

Malone-Lee JG, Al-Buheissi S. Does urodynamic verification of overactive bladder determine treatment success? Results from a randomized placebo-controlled study. BJU Int. 2009 Apr;103(7):931-7. doi: 10.1111/j.1464-410X.2009.08361.x. Epub 2009 Mar 5. — View Citation

Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int. 2001 Jun;87(9):760-6. Erratum in: BJU Int 2001 Nov;88(7):807. — View Citation

Mukerji G, Yiangou Y, Grogono J, Underwood J, Agarwal SK, Khullar V, Anand P. Localization of M2 and M3 muscarinic receptors in human bladder disorders and their clinical correlations. J Urol. 2006 Jul;176(1):367-73. — View Citation

Nazir J, Kelleher C, Aballéa S, Maman K, Hakimi Z, Mankowski C, Odeyemi I. Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta-analysi — View Citation

Nitti VW, Rovner ES, Bavendam T. Response to fesoterodine in patients with an overactive bladder and urgency urinary incontinence is independent of the urodynamic finding of detrusor overactivity. BJU Int. 2010 May;105(9):1268-75. doi: 10.1111/j.1464-410X — View Citation

Otsuka A, Shinbo H, Matsumoto R, Kurita Y, Ozono S. Expression and functional role of beta-adrenoceptors in the human urinary bladder urothelium. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):473-81. doi: 10.1007/s00210-008-0274-y. Epub 2008 Mar — View Citation

Ouslander JG. Management of overactive bladder. N Engl J Med. 2004 Feb 19;350(8):786-99. Review. — View Citation

Sekido N, Hinotsu S, Kawai K, Shimazui T, Akaza H. How many uncomplicated male and female overactive bladder patients reveal detrusor overactivity during urodynamic study? Int J Urol. 2006 Oct;13(10):1276-9. — View Citation

Sheng W, Zhang H, Ruth KH. Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis. Neurourol Urodyn. 2017 Sep;36(7):1703-1710. doi: 10.1002/nau.23210. Epub 2017 Jan 19. Review. — View Citation

Speakman M, Khullar V, Mundy A, Odeyemi I, Bolodeoku J. A cost-utility analysis of once daily solifenacin compared to tolterodine in the treatment of overactive bladder syndrome. Curr Med Res Opin. 2008 Aug;24(8):2173-9. doi: 10.1185/03007990802234829. Ep — View Citation

Steers WD, Kolbeck S, Creedon D, Tuttle JB. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest. 1991 Nov;88(5):1709-15. — View Citation

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Takeda M, Obara K, Mizusawa T, Tomita Y, Arai K, Tsutsui T, Hatano A, Takahashi K, Nomura S. Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods. J Phar — View Citation

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* Note: There are 43 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in participant's urinary beta-3 adrenoreceptor from baseline to 12 weeks after treatment	Concentrations of urinary beta-3 adrenoceptor levels will be analyzed for 1)before and after treatment of patients with overactive bladder syndrome treated with Mirabegron; 2)before and after treatment patients with overactive bladder syndrome treated with Solifenacin; 3)patients with urinary tract infection, and 4)control (subjects without lower urinary tract symptoms).	12 weeks
Secondary	Effect of treatment with Mirabegron in patients with overactive bladder with or without detrusor overactivity after 12 weeks of treatment	Individual participant's change score on Overactive Bladder Symptom Score (OABSS) will be compared between participants treated with Mirabegron with and without detrusor overactivity after 12 weeks of treatment. The OABSS is a validated symptom questionnaire that sums the score of four symptoms (daytime frequency, nighttime frequency, urgency, and urgency incontinence). The total score ranges from 0 to 15, with higher the number, the greater the symptoms are.	12 weeks
Secondary	Effect of treatment with Mirabegron in patients with overactive bladder with or without detrusor overactivity 6 months after treatment.	Individual participant's change score on Overactive Bladder Symptom Score (OABSS) will be compared between participants treated with Mirabegron with and without detrusor overactivity 6 months after treatment. The OABSS is a validated symptom questionnaire that sums the score of four symptoms (daytime frequency, nighttime frequency, urgency, and urgency incontinence). The total score ranges from 0 to 15, with higher the number, the greater the symptoms are.	6 months
Secondary	Change in impact on the participant's life after treatment with Mirabegron with overactive bladder with or without detrusor overactivity after 12 weeks of treatment.	Individual participant's change score on the Overactive Bladder Questionnaire short-form (OAB-q SF) will be compared between participants treated with Mirabegron with and without detrusor overactivity after 12 weeks of treatment. The OAB-q SF assess the impact of OAB symptoms on the patient's life, and consists of symptom-bother and health-related quality of life. The subscales are summed and transformed into scores ranging from 0 to 100; a high symptom-bother score indicates greater symptom severity and a high health-related quality of life scale score indicates higher quality of life.	12 weeks
Secondary	Change in impact on the participant's life after treatment with Mirabegron with overactive bladder with or without detrusor overactivity 6 months after treatment	Individual participant change score on the Overactive Bladder Questionnaire short-form (OAB-q SF) will be compared between participants treated with Mirabegron with and without detrusor overactivity 6 months after treatment. The OAB-q SF assess the impact of OAB symptoms on the patient's life, and consists of symptom-bother and health-related quality of life. The subscales are summed and transformed into scores ranging from 0 to 100; a high symptom-bother score indicates greater symptom severity and a high health-related quality of life scale score indicates higher quality of life.	6 months
Secondary	Effect on the participant's life after treatment with Mirabegron with overactive bladder with or without detrusor overactivity after 12 weeks of treatment.	Individual participant's change score on Short Form Health Survey (SF-12) will be compared between participants treated with Mirabegron with and without detrusor overactivity after 12 weeks of treatment. SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. The score is converted to a range of 0 to 100, with high the score indicating a better quality of life.	12 weeks
Secondary	Effect on the participant's life after treatment with Mirabegron with overactive bladder with or without detrusor overactivity 6 months after treatment.	Individual participant's change score on Short Form Health Survey (SF-12) will be compared between participants treated with Mirabegron with and without detrusor overactivity 6 months after treatment. SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. The score is converted to a range of 0 to 100, with high the score indicating a better quality of life.	6 months
Secondary	The participant's subjective measurement of treatment outcome with Mirabegron with overactive bladder with or without detrusor overactivity after 12 weeks of treatment.	Individual participant's change score on Global Response Assessment Scale (GRAS) will be compared between participants treated with Mirabegron with and without detrusor overactivity after 12 weeks of treatment. GRAS is a subjective outcome measurement to asses the participant's perception of treatment success. The score is scaled from 0 to 100%, with greater the percentage, the greater improvement of symptoms after treatment is perceived.	12 weeks
Secondary	The participant's subjective measurement of treatment outcome with Mirabegron with overactive bladder with or without detrusor overactivity 6 months after treatment.	Individual participant's change score on Global Response Assessment Scale (GRAS) will be compared between participants treated with Mirabegron with and without detrusor overactivity 6 months after treatment. GRAS is a subjective outcome measurement to asses the participant's perception of treatment success. The score is scaled from 0 to 100%, with greater the percentage, the greater improvement of symptoms after treatment is perceived.	6 months
Secondary	Comparison of the effect of treatment with Mirabegron and Solifenacin in patients with overactive bladder after 12 weeks of treatment	Individual participant's change score on Overactive Bladder Symptom Score (OABSS) will be compared between participants treated with Mirabegron and Solifenacin in patients with overactive bladder after 12 weeks of treatment. The OABSS is a validated symptom questionnaire that sums the score of four symptoms (daytime frequency, nighttime frequency, urgency, and urgency incontinence). The total score ranges from 0 to 15, with higher the number, the greater the symptoms are.	12 weeks
Secondary	Comparison of the effect of treatment with Mirabegron and Solifenacin in patients with overactive bladder 6 months after treatment.	Individual participant's change score on Overactive Bladder Symptom Score (OABSS) will be compared between participants treated with Mirabegron and Solifenacin in patients with overactive bladder 6 months after treatment. The OABSS is a validated symptom questionnaire that sums the score of four symptoms (daytime frequency, nighttime frequency, urgency, and urgency incontinence). The total score ranges from 0 to 15, with higher the number, the greater the symptoms are.	6 months
Secondary	Comparison of the impact of symptoms on life with Mirabegron and Solifenacin in patients with overactive bladder after 12 weeks of treatment	Individual participant change score on the Overactive Bladder Questionnaire short-form (OAB-q SF) will be compared between participants treated with Mirabegron and Solifenacin in patients with overactive bladder after 12 weeks of treatment. The OAB-q SF assess the impact of OAB symptoms on the patient's life, and consists of symptom-bother and health-related quality of life. The subscales are summed and transformed into scores ranging from 0 to 100; a high symptom-bother score indicates greater symptom severity and a high health-related quality of life scale score indicates higher quality of life.	12 weeks
Secondary	Comparison of the impact of symptoms on life with Mirabegron and Solifenacin in patients with overactive bladder 6 months after treatment	Individual participant change score on the Overactive Bladder Questionnaire short-form (OAB-q SF) will be compared between participants treated with Mirabegron and Solifenacin in patients with overactive bladder 6 months after treatment. The OAB-q SF assess the impact of OAB symptoms on the patient's life, and consists of symptom-bother and health-related quality of life. The subscales are summed and transformed into scores ranging from 0 to 100; a high symptom-bother score indicates greater symptom severity and a high health-related quality of life scale score indicates higher quality of life.	6 months
Secondary	Effect on the participant's life after treatment with Mirabegron and Solifenacin after 12 weeks of treatment.	Individual participant's change score on Short Form Health Survey (SF-12) will be compared between participants treated with Mirabegron and Solifenacin after 12 weeks of treatment. SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. The score is converted to a range of 0 to 100, with high the score indicating a better quality of life.	12 weeks
Secondary	Effect on the participant's life after treatment with Mirabegron and Solifenacin 6 months after treatment.	Individual participant's change score on Short Form Health Survey (SF-12) will be compared between participants treated with Mirabegron and Solifenacin 6 months after treatment. SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. The score is converted to a range of 0 to 100, with high the score indicating a better quality of life.	6 months
Secondary	The participant's subjective measurement of treatment outcome with Mirabegron and Solifenacin after 12 weeks of treatment.	Individual participant's change score on Global Response Assessment Scale (GRAS) will be compared between participants treated with Mirabegron and Solifenacin after 12 weeks of treatment. GRAS is a subjective outcome measurement to asses the participant's perception of treatment success. The score is scaled from 0 to 100%, with greater the percentage, the greater improvement of symptoms after treatment is perceived.	12 weeks
Secondary	The participant's subjective measurement of treatment outcome with Mirabegron and Solifenacin 6 months after treatment.	Individual participant's change score on Global Response Assessment Scale (GRAS) will be compared between participants treated with Mirabegron and Solifenacin 6 months after treatment. GRAS is a subjective outcome measurement to asses the participant's perception of treatment success. The score is scaled from 0 to 100%, with greater the percentage, the greater improvement of symptoms after treatment is perceived.	6 months