Beta-3 Agonist and Anti-muscarinic Agent for Sjogren's Syndrome With Overactive Bladder

The Therapeutic Effect of Beta-3 Agonist and Anti-muscarinic Agent on Overactive Bladder Among Sjogren's Syndrome Patient

Overactive bladder is more prevalent among the Sjogren syndrome's population compare to the general population. Both anti-muscarinic agent and beta-3 agonist are recommended as second line treatment for overactive bladder syndrome. However, theoretically, undesirable effect of the anti-muscarinic agent such as dry mouth and constipation would make it less suitable for Sjogren syndrome patient with overactive bladder. Therefore, this study is a randomised control study with the aim to evaluate the therapeutic effect of beta-3 agonist and anti-muscarinic agent on overactive bladder among sjogren's syndrome patient.

Study Overview

• Status: Recruiting
• Conditions: Sjogren's Syndrome; Overactive Bladder Syndrome
• Intervention / Treatment: Drug: oxybutynin, tolterodine, solifenacin; Drug: mirabegron

Detailed Description

Overactive bladder(OAB) is a syndrome characterized by the presence of frequency, urgency, nocturia, and with or without urgency urinary incontinence. The reported prevalence of overactive bladder was similar between man and woman. An overactive bladder has been shown to impair the quality of life of the patient. Muscarinic receptors, particularly M2 and M3 receptors were involved in detrusor contraction. Anti-muscarinic receptor drugs, such as oxybutynin and tolterodine are drugs that are currently recommended by both European association of Urology(EAU) and American Urology Association(AUA) guidelines as a second-line treatment for OAB. Beta-3 agonist such as mirabegron is another medication that is commonly used for OAB. Beta-3 agonists increased the bladder capacity of OAB patients without impairing the detrusor contractility.

Sjogren syndrome(Ss) is an autoimmune disease that frequently affects the lacrimal gland and salivary gland causing the patient to have dry mouth and dry eyes. Extraglandular manifestation was also present. Genitourinary manifestation such as frequency, urgency, and vaginal dryness have been reported but not extensively studied. Currently, there is no consensus for the management of these extraglandular manifestations.

Several studies have reported an increasing prevalence of lower urinary tract symptoms in Ss. Detrusor overactivity was the most commonly found based on a small study. A nationwide population-based study in Taiwan has shown that the risk of developing OAB in the Ss population is significantly higher than the control group.

Cholinesterase inhibitors like pilocarpine and muscarinic agonists such as cevimeline are common drugs used to treat dry eyes and dry mouth of Sjogren syndrome while anti-muscarinic drugs are extensively used to treat OAB. Pilocarpine works by increasing acetylcholine concentration in the synaptic junction while cevimeline works as a muscarinic receptor. Whether the increased prevalence of OAB in Ss population is due to the medication itself or due to the disease is not clear. Currently, there is no study investigating the optimal management of lower urinary tract symptoms(LUTS) in Sjogren Syndrome populations.

Objective The objective of this study is to investigate the effect of muscarinic agonists used for Ss on LUTS and the efficacy of beta3 agonists for management OAB in Ss.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hao Xiang Cen, MD; Phone Number: 224043 (04)2205 - 2121; Email: lylemushroom@gmail.com
• Study Contact Backup: Name: Chieh-Lung Chou, MD; Phone Number: (04)2205 - 2121

Study Locations

• Taiwan
  • Taichung, Taiwan, 40421
    • Recruiting
    • China Medical University Hospital
    • Contact: Hao Xiang Chen, MD; Phone Number: 224043 (04)2205 - 2121; Email: lylemushroom@gmail.com
    • Contact: Chieh-lung Chou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Sjogren's syndrome AND
• Clinical diagnosis of OAB

Exclusion Criteria:

• Congenital or acquired anatomic abnormalities of the genitourinary tract,
• Uncontrolled severe hypertension >180 mmHg
• Cannot cooperate for voiding diary documentation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antimuscarinic; oxybutynin, tolterodine, solifenacin	Drug: oxybutynin, tolterodine, solifenacin; use anti-muscarinic agent for patient with overactive bladder syndrome; Other Names: Ditropan, tartrate, vesicare
Experimental: B3-agonist; mirabegron	Drug: mirabegron; use beta-3 agonist for sjogren syndrome patient; Other Names: Betmiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overactive bladder symptom score	0-15, higher means worse outcome	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
uroflowmetry	curve shape	3 months
Frequency of void	defined as the number of voiding per day	3 months
International Prostate Symptom Score	0-35, with higher means worse outcome	3 months
EULAR Sjogren's Syndrome Patient Reported Index	0-30, with higher means worse outcome	3 months
Post-void residual	the residual bladder volume after voiding, in mL	3months
Average speed	in ml/s, the average speed of voiding as measured by uroflowmetry	3months

Collaborators and Investigators

• Sponsor: China Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Anticipated): August 15, 2022
• Study Completion (Anticipated): August 15, 2022

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 8, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Eye Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Urinary Bladder, Overactive; Syndrome; Sjogren's Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Oxybutynin; Mirabegron; Solifenacin Succinate; Tolterodine Tartrate
• Other Study ID Numbers: CMUH109-REC2-200

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No