Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01003249
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder; Constipation; Lower Urinary Tract Symptoms	Drug: Baclofen; Drug: Placebo	Phase 4

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Treatment of Patients With Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen: a Randomized Double-blind Placebo-controlled Cross-over Trial
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: 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.; 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.
Placebo Comparator: 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	Drug: 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.; 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.

Outcome Measures

Primary Outcome Measures

1. Urine Flow Rate, as Measured With Uroflometry [Baseline and 4 weeks]

   Uroflometry with patch electrodes will also be completed at the end of this four week period. Higher flow rate denotes better outcome.

2. Number of Participants Exhibiting Abnormal EMG Activity During Voiding [Baseline and 4 weeks]

   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.

3. Average Scores on International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol) [Baseline and 4 weeks]

   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.

4. Average Scores on Dysfunctional Voiding as Measured With Quality of Life (QOL) Questionnaire [Baseline and 4 weeks]

   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.

Secondary Outcome Measures

1. Number (and Percentage) of Participants With External Anal Sphincter Muscle Dysfunction Via Patient Symptoms. [Baseline and 4 weeks]

   The percent of patient in each group who had defecation problem

2. Efficacy of Baclofen vs. Placebo on Number of Voidings Per Day [Baseline and 4 weeks]

   The number of voiding per day before and after treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

• Principal Investigator: Gopal Badlani, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01003249
• Other Study ID Numbers: IRB00009516
• First Posted: Oct 28, 2009
• Last Update Posted: Aug 14, 2018
• Last Verified: Jul 1, 2018

• 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
• Keywords provided by Wake Forest University Health Sciences: over distention of bladder; Dysfunctional voiding; dysfunctional elimination syndrome
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Constipation; Lower Urinary Tract Symptoms; Baclofen

Study Results

Participant Flow

Arm/Group Title	Baclofen, Then Placebo	Placebo, Then Baclofen
Arm/Group Description	Participants first received Baclofen for a total of 2 weeks (beginning dose=10mg and dose escalated up to 80 mg as symptoms appear), and were then tapered off of Baclofen for 2 weeks (total time= 4 weeks). This was followed by a 3 week washout period and then 4 weeks of Placebo.	Participants received Placebo for 4 weeks, followed by a 3 week washout period. Participants then received Baclofen for a total of 2 weeks (beginning dose=10mg and dose escalated up to 80 mg as symptoms appear), and were then tapered off of Baclofen for 2 weeks (total time= 4 weeks).
Period Title: First Intervention (4 Weeks)
STARTED	7	5
Received Intervention	7	5
COMPLETED	5	3
NOT COMPLETED	2	2
Period Title: First Intervention (4 Weeks)
STARTED	4	3
COMPLETED	4	3
NOT COMPLETED	0	0
Period Title: First Intervention (4 Weeks)
STARTED	4	3
COMPLETED	3	2
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Includes all participants in the study. Participants were randomized to either study drug or placebo
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Sex/Gender, Customized (Count of Participants)
Female	3 25%
Male	2 16.7%
Unknown	7 58.3%
Region of Enrollment (Count of Participants)
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Urine Flow Rate, as Measured With Uroflometry
Description	Uroflometry with patch electrodes will also be completed at the end of this four week period. Higher flow rate denotes better outcome.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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). 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).	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). Placebo Comparator: 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).
Measure Participants	12	12
Baseline	7.9 (1.93)	8.4 (1.7)
After Treatment	10.1 (3.01)	8.9 (2.05)

2. Primary Outcome

Title	Number of Participants Exhibiting Abnormal EMG Activity During Voiding
Description	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.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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).	Placebo Comparator: 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).
Measure Participants	12	12
Baseline	6 50%	6 NaN
After Treatment	4 33.3%	6 NaN

3. Primary Outcome

Title	Average Scores on International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol)
Description	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.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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).	Placebo Comparator: 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).
Measure Participants	12	12
Baseline	165.3 (13.2)	174 (18.1)
After Treatment	120.7 (14.8)	160 (15.8)

4. Primary Outcome

Title	Average Scores on Dysfunctional Voiding as Measured With Quality of Life (QOL) Questionnaire
Description	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.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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).	Placebo Comparator: 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).
Measure Participants	12	12
Baseline	15.1 (3.23)	14.3 (3.70)
After Treatment	14.3 (2.56)	12.8 (3.25)

5. Secondary Outcome

Title	Number (and Percentage) of Participants With External Anal Sphincter Muscle Dysfunction Via Patient Symptoms.
Description	The percent of patient in each group who had defecation problem
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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).	Placebo Comparator: 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)
Measure Participants	12	12
Before Treatment	4 33.3%	3 NaN
After Treatment	2 16.7%	3 NaN

6. Secondary Outcome

Title	Efficacy of Baclofen vs. Placebo on Number of Voidings Per Day
Description	The number of voiding per day before and after treatment.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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).	Placebo Comparator: 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)
Measure Participants	12	12
Baseline	10.7 (2.93)	10.3 (2.85)
After Treatment	8.3 (1.98)	9.2 (2.27)

Adverse Events

Arm/Group Title	Baclofen		Placebo
Arm/Group Description	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). 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).		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). Placebo Comparator: 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).
All Cause Mortality
	Baclofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Baclofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/12 (0%)
Psychiatric disorders
Psychosis	1/12 (8.3%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Baclofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		2/12 (16.7%)
Gastrointestinal disorders
GI Symptoms	1/12 (8.3%)	1	1/12 (8.3%)	1
General disorders
Excessive Sleepiness	1/12 (8.3%)	1	2/12 (16.7%)	2
Musculoskeletal and connective tissue disorders
Feeling too loose	1/12 (8.3%)	1	2/12 (16.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.