Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen

NCT ID: NCT01003249

Last Updated: 2018-08-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2013-03-31

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)

1. Efficacy of baclofen vs. placebo on dysfunctional voiding as measured with uroflometry and EMG; patients' symptoms score questionnaires and diaries.

2. 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).

Conditions

Overactive Bladder; Constipation; Lower Urinary Tract Symptoms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Baclofen, Then Placebo

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

Group Type: ACTIVE_COMPARATOR

Baclofen

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Placebo, Then Baclofen

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

Group Type: PLACEBO_COMPARATOR

Baclofen

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Interventions

Baclofen

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gopal Badlani, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

IRB00009516

Identifier Type: -

Identifier Source: org_study_id