Efficacy and Safety of Gabapentin in Treating Overactive Bladder

Study Overview
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Brief Summary
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Overactive bladder (OAB) syndrome as defined by International Continence Society is a pathological condition characterized by irritative symptoms: urinary urgency, with or without incontinence, urinary frequency and nocturia. The syndrome often seriously compromises the quality of life of the patients. The etiology of the OAB is considered multifactorial. Neural plasticity of bladder afferent pathways is one of the proposed mechanisms of OAB. The detrusor muscle itself has for many years been the target for drug treatment such as antimuscarinics. However, depression of detrusor contractility, may results in a reduced ability to empty the bladder and lead to some sympathetic adverse effects, which limits the treatment of OAB. Currently the focus of OAB treatment has changed to other bladder structures/mechanisms, such as afferent nerves and urothelial signaling as targets for intervention. C-fiber bladder afferents nerves may be critical for symptom generation in pathologic states such as OAB because these fibers demonstrate remarkable plasticity. Up-regulation of bladder C-fiber afferent nerve function may also play a role in urge incontinence, overactive bladder (OAB) and sensory urgency. The mechanism of Gabapentin's action for neuropathic pain has not been fully elucidated but is appears to have inhibitory activity on afferent C-fibers nerve activity; moreover, several studies had established the safety of Gabapentin in its treatment of different conditions. Due to the proposed mechanism, the investigators suggest that Gabapentin may be a new alternative for treating OAB.

Official Title
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Efficacy and Safety of Gabapentin in Treating Overactive Bladder

Conditions
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Urinary Urgency, Urinary Frequency, Nocturia, Incontinence, Detrusor Uninhibited Activity, Quality of Life

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Solifenacin Succinate
* Drug: Placebo drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory and able to use the toilet without difficulty History of OAB symptoms for ≥ 3 months An average of ≥ 8 micturitions per 24 hours and ≥ 1 urgency episode (with or without incontinence) per 24 hours as documented in a 3-day micturition diary Subjects are bothered by symptoms as reflected by OAB-questionnaire Exclusion Criteria: Patient has stress or mixed incontinence Patient has Benign Prostatic Hyperplasia with severe lower urinary tract symptoms based on IPSS score Patient has uncontrolled Diabetes Mellitus Type II Patient has Diabetes Insipidus, UTI Patient has history of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain Patient has a history of stroke, seizures, or major neurological disorders Patient has a history of fecal incontinence and or continual urine leakage Patient has had surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months of study start Patient received bladder training of electrostimulation within 2 weeks of study start Patient requires a catheter Patient is taking medications that cannot be stopped for the duration of the trial including certain anticholinergics or smooth muscle relaxants Patient began taking tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, calcium channel blockers, ephedrine/pseudoephedrine, or diuretic therapy less than 8 weeks before study start Patient has been on hormone replacement therapy for less than 12 weeks at study start Patient must take medication for arrhythmia, contraindicated for Solifenacin or Gabapentin Patient has multiple and/or severe allergies to foods and drugs Patient regularly uses any illegal drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Gabapentin<br>Two to three months of behavioral therapy prior to start of Gabapentin 100mg/capsule, initially 1 capsule once a day for 1 week then titrate dosage according to symptoms until maximum dose of 1500mg/day Placebo tablet of Solifenacin Succinate will titrate dose same as Solifenacin arm according to symptoms of patient | Drug: Gabapentin<br>* 100mg/capsule initially one capsule once a day then titrate according to the symptoms of the patient upto maximum dose of 1500mg/day<br>|
| Active Comparator: Solifenacin Succinate<br>Two to three months of behavioral therapy prior to Solifenacin Succinate 5mg/tablet initially 1 tablet once a day then titrate dosage according to symptoms upto maximum dose of 10mg/day Placebo form of Gabapentin will titrate dosage same as Gabapentin group according to symptoms of patient | Drug: Solifenacin Succinate<br>* 5mg/tablet initially 1 tablet once a day then titrate up to maximum dose of 10mg/tab<br>|
| Placebo Comparator: Placebo<br>Two to three months of behavioral therapy prior to Placebo form of Gabapentin and Solifenacin and titrate accordingly same as the treatment arms | Drug: Placebo drugs<br>* will titrate medications similar to the active drug group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of symptom domain means decreased frequency to less than 8 micturitions per 24 hours, no urgency noted per 24 hrs and less that 3 wakening at bedtime for micturation. | Mean number of Micturations per 24 hrs, Mean number of urgency episodes pe 24 hrs, mean urgency incontinence episodes per 24hrs and mean nocturia episodes per 24hrs | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of bladder function domain means increased bladder capacity (MVV) |  | 12 weeks | 
| Improvement in quality of life domain means increased overall quality of life as perceived and result in OAB-q |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overactive Bladder, Gabapentin, Quality of Life, Urodynamic, safety, Efficacy