Beta 3 Agonists in Treatment of Non-neurogenic Voiding Dysfunction in Children

Study Overview
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Brief Summary
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A randomized clinical study to evaluate the safety and efficacy of using the Beta 3 agonist drug (Mirabegron) combined with standard behavioral therapy in comparison to using the anticholinergic drug (Solifenacin) combined with behavioral therapy, for children with non-neurogenic voiding dysfunction refractory to behavioral therapy alone, using improvement of dysfunctional voiding symptom score as a primary measurement of efficacy.

Detailed Description
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The study aims to evaluate the beta 3 agonist drug (Mirabegron) as regard its safety and efficacy when used in children with non neurogenic voiding dysfunction, including children suffering from frequency, urgency, urgency incontinence and hesitancy who do not have neurological disease explaining these symptoms and who failed behavioral urotherapy. The patients will be randomly allocated into two groups, one will receive standard behavioral therapy plus Mirabegron, the other will receive standard behavioral therapy plus the anticholinergic drug Solifenacin for three months. Patients will be assessed initially and after three months using: Medical and voiding history (bladder voiding diary, Dysfunctional voiding symptom score (DVSS) , Bristol Stool Scale) Dysfunctional voiding symptom score (DVSS) , Bristol Stool Scale Urine analysis and mid-stream urine culture. Uroflowmetry. Pelvic US and post-void residual urine (PVR).

Official Title
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Safety and Efficacy Beta 3 Agonists in Treatment of Non-neurogenic Voiding Dysfunction in Children, a Randomized Clinical Trial

Conditions
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Voiding Disorders, Overactive Bladder

Intervention / Treatment
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* Drug: Beta3-Agonists, Adrenergic
* Drug: Anticholinergic drug, Solifenacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with non-neurogenic voiding dysfunction predominantly filling phase dysfunctions or OAB, refractory to behavioral therapy as a primary monotherapy, with dysfunctional voiding symptom score of ≥6 for females and ≥9 for males, between the age of 5 & 18 years old. Exclusion Criteria: Neurogenic or anatomical bladder problems. Patients with contraindications to Beta 3 agonists or anticholinergic drugs.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>This arm will receive standard behavioral therapy plus Mirabegron with adjusted-dose regimen (25-50 mg), patients of 20-40 kg will receive 25-50 mg once a day; patients >40 kg will receive 50 mg once a day, for three months. | Drug: Beta3-Agonists, Adrenergic<br>* The beta 3 agonist ,Mirabegron, has been shown to be effective for the treatment of OAB in adults through relaxation of bladder wall, with few side effects. This intervention aims to evaluate its efficacy and safety for children with non-neurogenic voiding dysfunction.<br>* Other names: Standard behavioral Urotherapy;|
| Active Comparator: Control<br>This arm will receive will receive standard behavioral therapy plus Solifenacin with a daily dosage of (2.5-10 mg/kg), for three months. | Drug: Anticholinergic drug, Solifenacin<br>* Anticholinergic drugs are widely used to treat overactive bladder by relaxation of bladder wall smooth muscles.<br>* Other names: Standard behavioral Urotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the Beta 3 agonist drug (Mirabegron) in improving symptoms of children with voiding dysfunction using dysfunctional voiding scoring system as a primary measure. | To evaluate the efficacy of using the Beta 3 agonist drug (Mirabegron) combined with standard behavioral therapy in comparison to using the anticholinergic drug (Solifenacin) combined with behavioral therapy, for children with non-neurogenic voiding dysfunction refractory to behavioral therapy alone, using improvement of dysfunctional voiding symptom score as a primary measurement of efficacy. This score consists of 10 voiding dysfunction parameters that are assigned scores of 0 to 3 according to prevalence, and possible total scores ranging from 0 to 30. The higher the score, the more severe the symptoms of voiding dysfunction. The documented cutoff score for voiding dysfunction is 6 and 9 for females and males respectively. | 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the side effects of the beta 3 agonist drug (Mirabegron) in children. | This is planned to assess side effects and safety profile of the beta 3 agonist (Mirabegron) on children (5-18 years) from Egypt. | 6 months | 
| To validate an Arabic version of the Dysfunctional Voiding Scoring System as the documented cutoff score for voiding dysfunction is 6 and 9 for females and males respectively. | The investigators are planning to translate an Arabic version of the Dysfunctional Voiding Scoring System to use it to assess improvement of symptoms and patient recorded outcomes for Egyptian children before and after receiving Mirabegron. | 6 months | 
| To evaluate correlation between bladder ultrasound findings and severity of patients' symptoms. (normally it is less than 3 mm) | The investigators are planning to assess Ultrasound measurement of bladder wall thickness as an indicator of severity of patients' symptoms and whether there is bladder wall hypertrophy corresponding to severity of symptoms and whether the bladder wall thickness decreases with treatment. | 6 months |