Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen

Study Overview
=================
Brief Summary
-----------------
Dysfunctional voiding is often associated with constipation. The association of constipation with urologic pathologic processes has previously been described since the 1950's, but it was only over the past decade that clinicians have paid more attention to this relationship and recognized it existence with the term dysfunctional elimination syndrome (DES). This term is used to reflect the broad spectrum of functional disturbances that may affect the urinary tract including that of functional bowl disturbances and can be classified as follows: Functional disorder of filling: overactive bladder, over distention of bladder or insensate bladder, which may be associated with fecal impaction or rectal distention with infrequent bowel movements Functional disorder of emptying: over-recruitment of pelvic floor activity during voiding causing interrupted and/or incomplete emptying also associated with defecation difficulties due to non- relaxation of the puborectalis muscle, dyssynergic defecation or pain with defecation Several different therapeutic options have been used for patients with dysfunctional voiding mainly to decrease bladder outlet obstruction. These treatments including, alpha adrenergic antagonists, and botulinum toxin are less than optimum. One possible explanation for these drug failures includes the inability of these medications to relax the striated muscles of the pelvic floor necessary for voiding. To date there has been no data to evaluate the role of baclofen on the striated muscle of the external anal sphincter, essential in the defecation process.

Detailed Description
-----------------
Outcome Measure(s) Efficacy of baclofen vs. placebo on dysfunctional voiding as measured with uroflometry and EMG; patients' symptoms score questionnaires and diaries. Efficacy of baclofen vs. placebo on the external anal sphincter muscle dysfunction via patient symptoms and questionnaire. 3. The safety of baclofen in patients with dysfunctional voiding (urinary and defecatory).

Official Title
-----------------
Treatment of Patients With Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen: a Randomized Double-blind Placebo-controlled Cross-over Trial

Conditions
-----------------
Constipation, Overactive Bladder, Lower Urinary Tract Symptoms

Intervention / Treatment
-----------------
* Drug: Baclofen
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult men and women (>18 years old, <65 years old) Patients with lower urinary tract symptoms (hesitancy, intermittency decreased force and caliber of urinary stream, urgency, incontinence) and urodynamic finding compatible with diagnosis of DV in multichannel videourodynamics. (Non relaxation or over stimulation of EMG activity, and stress pattern of voiding) Established symptoms for at least six months Patients with defecatory symptom should have symptoms of constipation (must include 2 or more of the following: straining during 25% of defecations, hard or lumpy stools during 25% of defecation, sensation of incomplete evacuation upon defecations, sensation of anorectal blockage or obstruction during 25% of defecations, manual maneuvers to facilitate 25% of defecations; loose stools that are rarely present without the use of laxatives; insufficient criteria to meet the definition of IBS-C. Exclusion Criteria: Overt neurogenic disease Significant bladder outlet obstruction Detrusor instability on Urodynamic study Detrusor hypo contractility due to neurogenic causes Previous pelvic radiation Present (and past) malignancy of bladder or prostate Present or recurrent UTI (3 or more documented UTI in the past year ) Interstitial Cystitis Diabetic neuropathy Patients on anticholinergic medications Bladder stones Urinary retention Underlying dementia or significant cognitive impairment. Patients unwilling to undergo videourodynamic , EMG or anorectal manometry testing Sample size: 62 patients in total (calculation basis described on Statistical Plan for Data Analysis)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Baclofen, Then Placebo<br>Subjects will then randomly be assigned in placebo or baclofen groups. Daily dose will be doubled every three days, up to 80 mg or when side effects appear. There will be a washout period after three week. At the end of 4 week drug will be tapered (halved every 2 days and quitted after 2 days of using 20 mg baclofen). Then patients initially assigned to the baclofen group will be assigned to the placebo group, and those assigned to the placebo group will be assigned to the baclofen group. Patients would then receive a dose of baclofen 10 mg PO twice daily (or placebo twice daily), and then the dose will be escalated to 80 mg | Drug: Baclofen<br>* Subjects will be randomly assigned to placebo or baclofen groups. Daily dose will be doubled every three days, up to 80 mg or when side effects appear. At the end of 4 week drug will be tapered (halved every 2 days and quitted after 2 days of using 20 mg baclofen). After the 3 week washout period, questionnaires, diary, EMG and uroflowmetry will be repeated. Then patients initially assigned to the baclofen group will be assigned to the placebo group, and those assigned to the placebo group will be assigned to the baclofen group. Patients would then receive a dose of baclofen 10 mg PO twice daily (or placebo twice daily), and then the dose will be escalated to 80 mg.<br>Drug: Placebo<br>* Subjects will then randomly be assigned in placebo or baclofen groups. Daily dose will be doubled every three days, up to 80 mg or when side effects appear. At the end of 4 week drug will be tapered (halved every 2 days and quitted after 2 days of using 20 mg baclofen). After the 3 week washout period, questionnaires, diary, EMG and uroflowmetry will be repeated. Then patients initially assigned to the baclofen group will be assigned to the placebo group, and those assigned to the placebo group will be assigned to the baclofen group. Patients would then receive a dose of baclofen 10 mg PO twice daily (or placebo twice daily), and then the dose will be escalated to 80 mg.<br>|
| Placebo Comparator: Placebo, Then Baclofen<br>Subjects will then randomly be assigned in placebo or baclofen groups. Daily dose will be doubled every three days, up to 80 mg or when side effects appear. There will be a washout period after three week. At the end of 4 week drug will be tapered (halved every 2 days and quitted after 2 days of using 20 mg baclofen). Then patients initially assigned to the baclofen group will be assigned to the placebo group, and those assigned to the placebo group will be assigned to the baclofen group. Patients would then receive a dose of baclofen 10 mg PO twice daily (or placebo twice daily), and then the dose will be escalated to 80 mg | Drug: Baclofen<br>* Subjects will be randomly assigned to placebo or baclofen groups. Daily dose will be doubled every three days, up to 80 mg or when side effects appear. At the end of 4 week drug will be tapered (halved every 2 days and quitted after 2 days of using 20 mg baclofen). After the 3 week washout period, questionnaires, diary, EMG and uroflowmetry will be repeated. Then patients initially assigned to the baclofen group will be assigned to the placebo group, and those assigned to the placebo group will be assigned to the baclofen group. Patients would then receive a dose of baclofen 10 mg PO twice daily (or placebo twice daily), and then the dose will be escalated to 80 mg.<br>Drug: Placebo<br>* Subjects will then randomly be assigned in placebo or baclofen groups. Daily dose will be doubled every three days, up to 80 mg or when side effects appear. At the end of 4 week drug will be tapered (halved every 2 days and quitted after 2 days of using 20 mg baclofen). After the 3 week washout period, questionnaires, diary, EMG and uroflowmetry will be repeated. Then patients initially assigned to the baclofen group will be assigned to the placebo group, and those assigned to the placebo group will be assigned to the baclofen group. Patients would then receive a dose of baclofen 10 mg PO twice daily (or placebo twice daily), and then the dose will be escalated to 80 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Flow Rate, as Measured With Uroflometry | Uroflometry with patch electrodes will also be completed at the end of this four week period. Higher flow rate denotes better outcome. | Baseline and 4 weeks | 
| Number of Participants Exhibiting Abnormal EMG Activity During Voiding | EMG with patch electrodes was completed at the end of this four week period. The number of participants with EMG activity during voiding was collected. EMG activity during the voiding is considered abnormal and is a criteria for voiding dysfunction.Lower numbers denotes better outcomes. | Baseline and 4 weeks | 
| Average Scores on International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol) | Diagnosis of dysfunctional bladder is based on symptoms demonstrating no relaxation or over stimulation of external urinary sphincter during voiding. Symptoms will be scored by International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol). The ICIQ-LUTSqol is a patient-completed questionnaire for evaluating quality of life (QoL) in urinary incontinent patients There are 20 items and the score range is 10-200. Higher scores denotes better outcomes. | Baseline and 4 weeks | 
| Average Scores on Dysfunctional Voiding as Measured With Quality of Life (QOL) Questionnaire | This was measured using the Urogenital Distress Inventory (UDI-6). The UDI-6 is a symptom inventory specific to lower urinary tract dysfunction and genital prolapse. There are 6 items scored. The score range is from 0-100 Lower scores denotes better outcomes. | Baseline and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (and Percentage) of Participants With External Anal Sphincter Muscle Dysfunction Via Patient Symptoms. | The percent of patient in each group who had defecation problem | Baseline and 4 weeks | 
| Efficacy of Baclofen vs. Placebo on Number of Voidings Per Day | The number of voiding per day before and after treatment. | Baseline and 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
over distention of bladder, Dysfunctional voiding, dysfunctional elimination syndrome