Trial Outcomes & Findings for Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen (NCT NCT01003249)

NCT ID: NCT01003249

Last Updated: 2018-08-14

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 12 participants
• Primary outcome timeframe: Baseline and 4 weeks
• Results posted on: 2018-08-14

Participant Flow

Participant milestones

Measure	Baclofen, Then Placebo 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.	Placebo, Then Baclofen 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).
First Intervention (4 Weeks) STARTED	7	5
First Intervention (4 Weeks) Received Intervention	7	5
First Intervention (4 Weeks) COMPLETED	5	3
First Intervention (4 Weeks) NOT COMPLETED	2	2
Washout (3 Weeks) STARTED	4	3
Washout (3 Weeks) COMPLETED	4	3
Washout (3 Weeks) NOT COMPLETED	0	0
Second Intervention (4 Weeks) STARTED	4	3
Second Intervention (4 Weeks) COMPLETED	3	2
Second Intervention (4 Weeks) NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Baclofen, Then Placebo 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.	Placebo, Then Baclofen 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).
First Intervention (4 Weeks) Withdrawal by Subject	1	1
First Intervention (4 Weeks) Non-Serious Event	1	1
Second Intervention (4 Weeks) Withdrawal by Subject	0	1
Second Intervention (4 Weeks) Adverse Event	1	0

Baseline Characteristics

Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen

Baseline characteristics by cohort

Measure	All Participants n=12 Participants Includes all participants in the study. Participants were randomized to either study drug or placebo
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex/Gender, Customized Female	3 Participants n=5 Participants
Sex/Gender, Customized Male	2 Participants n=5 Participants
Sex/Gender, Customized Unknown	7 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Baclofen n=12 Participants 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).	Placebo n=12 Participants 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).
Urine Flow Rate, as Measured With Uroflometry Baseline	7.9 ml/s Standard Deviation 1.93	8.4 ml/s Standard Deviation 1.7
Urine Flow Rate, as Measured With Uroflometry After Treatment	10.1 ml/s Standard Deviation 3.01	8.9 ml/s Standard Deviation 2.05

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Baclofen n=12 Participants 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).	Placebo n=12 Participants 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).
Number of Participants Exhibiting Abnormal EMG Activity During Voiding Baseline	6 Participants	6 Participants
Number of Participants Exhibiting Abnormal EMG Activity During Voiding After Treatment	4 Participants	6 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Baclofen n=12 Participants 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).	Placebo n=12 Participants 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).
Average Scores on International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol) Baseline	165.3 scores on a scale Standard Deviation 13.2	174 scores on a scale Standard Deviation 18.1
Average Scores on International Consultation on Incontinence Modular Questionnaire- Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol) After Treatment	120.7 scores on a scale Standard Deviation 14.8	160 scores on a scale Standard Deviation 15.8

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Baclofen n=12 Participants 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).	Placebo n=12 Participants 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).
Average Scores on Dysfunctional Voiding as Measured With Quality of Life (QOL) Questionnaire Baseline	15.1 scores on a scale Standard Deviation 3.23	14.3 scores on a scale Standard Deviation 3.70
Average Scores on Dysfunctional Voiding as Measured With Quality of Life (QOL) Questionnaire After Treatment	14.3 scores on a scale Standard Deviation 2.56	12.8 scores on a scale Standard Deviation 3.25

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The percent of patient in each group who had defecation problem

Outcome measures

Measure	Baclofen n=12 Participants 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).	Placebo n=12 Participants 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).
Number (and Percentage) of Participants With External Anal Sphincter Muscle Dysfunction Via Patient Symptoms. Before Treatment	4 Participants	3 Participants
Number (and Percentage) of Participants With External Anal Sphincter Muscle Dysfunction Via Patient Symptoms. After Treatment	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline and 4 weeks

The number of voiding per day before and after treatment.

Outcome measures

Measure	Baclofen n=12 Participants 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).	Placebo n=12 Participants 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).
Efficacy of Baclofen vs. Placebo on Number of Voidings Per Day Baseline	10.7 number of voids Standard Deviation 2.93	10.3 number of voids Standard Deviation 2.85
Efficacy of Baclofen vs. Placebo on Number of Voidings Per Day After Treatment	8.3 number of voids Standard Deviation 1.98	9.2 number of voids Standard Deviation 2.27

Adverse Events

Baclofen

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Baclofen n=12 participants at risk 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).	Placebo n=12 participants at risk 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).
Psychiatric disorders Psychosis	8.3% 1/12 • Number of events 1	0.00% 0/12

Other adverse events

Measure	Baclofen n=12 participants at risk 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).	Placebo n=12 participants at risk 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).
Gastrointestinal disorders GI Symptoms	8.3% 1/12 • Number of events 1	8.3% 1/12 • Number of events 1
General disorders Excessive Sleepiness	8.3% 1/12 • Number of events 1	16.7% 2/12 • Number of events 2
Musculoskeletal and connective tissue disorders Feeling too loose	8.3% 1/12 • Number of events 1	16.7% 2/12 • Number of events 2

Additional Information

Dr. Gopal Badlani

Wake Forest University Health Sciences

Phone: 3367165928

Email: gbadlani@wakehealth.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place