Overactive Bladder
Conditions
Keywords
Overactive bladder, Behavioral treatment, Drug therapy, Lower urinary tract symptoms, Urinary incontinence, Clinical trial
Brief summary
The primary purpose of this project is to evaluate the effectiveness of behavioral treatment compared to standard drug therapy for symptoms of OAB in male veterans.
Detailed description
Overactive bladder (OAB) is a very common and bothersome condition manifested by urgency, frequent urination, urge urinary incontinence, and nocturia. Drug therapy with oxybutynin or tolterodine is the most common approach to treatment of OAB in VA Medical Center clinics and is the standard of care nationally. Although it improves symptoms of OAB for many patients, drug therapy often has side effects, which cause a significant number of patients to discontinue therapy. Further, many symptoms are not completely controlled, even while patients are on the medication. Therefore, there is a need to improve interventions for this common problem. Although behavioral treatment is a well-established treatment for urge urinary incontinence and frequency in women, there are no controlled trials of behavioral treatment for symptoms of OAB in men. The primary purpose of this project is to evaluate the effectiveness of behavioral treatment for symptoms of OAB in male veterans. The study is a two-site (Birmingham and Atlanta) randomized clinical trial to evaluate the effects of behavioral training compared to a standard (drug) treatment control condition. Subjects are 143 men with OAB as manifested by urgency and frequent urination (\>8 voids per day), with or without incontinence, and without significant bladder outlet obstruction. Following a run-in period in which all patients are treated with an alpha blocker to empirically treat any undetected obstruction, they are stratified on severity and presence of urge incontinence and randomized to 8 weeks of behavioral treatment or drug therapy. The behavioral treatment is a comprehensive, behavioral training program, which includes pelvic floor muscle rehabilitation, self monitoring with bladder diaries, and teaching urge suppression and other skills to inhibit detrusor contraction, thus reducing urgency, frequency, incontinence, and nocturia. Patients in the control group receive standard therapy consisting of individually titrated, extended-release oxybutynin, a well-established pharmacologic agent with a state of the art drug delivery system that has the lowest rates of side effects. Bladder diaries completed by subjects prior to randomization and following the last treatment session are used to calculate changes in frequency of urination, as well as other symptoms of overactive bladder, including reports of urgency, incontinence, and nocturia. Secondary outcome measures include patient global ratings of satisfaction and improvement, impact of incontinence, and the American Urological Association (AUA) Symptom Index. The second purpose of the study is to examine combined behavioral and drug therapy. Following post-treatment assessment, patients who do not achieve satisfactory outcomes with either behavioral or drug therapy alone are crossed over into a second phase, in which they receive combined treatment to improve outcome as much as possible. This study will yield important information related to alternative treatment of OAB in male veterans. Though many clinicians use drug therapy routinely in the treatment of OAB, most do not offer behavioral treatments such as pelvic floor muscle training for this problem. Thus, this study has potential to alter standards of care for OAB in men.
Interventions
BEHAVIORALBehavioral training
Comprehensive behavioral training program using delayed voiding, urge suppression techniques, pelvic floor muscle training, and monitoring with bladder diaries. Treatment is implemented by a nurse practitioner in 4 clinic visits over 8 weeks.
DRUGOxybutynin chloride, extended-release
Individually titrated, extended-release oxybutynin chloride, initiated at 10 mg, fluid management handout, and monitoring with bladder diaries. Treatment is implemented by a nurse practitioner in 4 clinic visits over 8 weeks.
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male * Community-dwelling * Veteran * Self-reported urgency * Self-reported frequent urination * Mean of \> 8 voids per 24-hour day on bladder diary * Able to come to clinic
Exclusion criteria
* Urologic surgery in the past 6 months * Nonambulatory (unless has independent transfer skills) * Flow rate \< 5mL at baseline and \< 10mL/sec after run-in (on simple uroflowmetry) * Post-void residual urine volume \> 250mL at baseline and \> 150mL after run-in (on bladder ultrasound) * Continual leakage * Urinary tract infection (growth of \> 100,000 colonies per ml of a urinary pathogen on urine culture). May be reconsidered after treatment and negative culture. * Fecal impaction * Poorly controlled diabetes (glycosylated hemoglobin \>9 within last 3 months) * Hematuria on microscopic examination in the absence of infection * Any unstable medical condition (particularly: decompensated congestive heart failure, malignant arrhythmias, unstable angina) \-- Impaired mental status (\< 24 on Folstein's Mini-Mental State Exam) * Narrow angle glaucoma * Gastric retention (by medical history) * Hypersensitivity to tamsulosin or oxybutynin * Current use of anticholinergic agents for detrusor instability. May be reconsidered after 2-week wash-out. * If on diuretic, dose has not been stable for at least three months * Sleep apnea, unless surgically corrected
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Voiding Frequency | post-treatment (week 8) | Mean voiding frequency per 24 hours derived from 7-day bladder dairy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urgency Severity | baseline to post-treatment (week 8) | Indevus Urgency Severity Scale incorporated into the 7-day bladder diary. Scores for urgency severity ranged from 0 to 3: 0: None-no urgency 1. Mild-awareness of urgency, but is easily tolerated. 2. Moderate-enough urgency discomfort that it interferes with or shortens usual activity 3. Severe-extreme urgency discomfort that abruptly stops all activities or tasks. |
| Percent Change in Frequency of Urge Incontinence | baseline to post-treatment (week 8) | Percent change in frequency of urge incontinence episodes based on 7-day bladder diary. Percent change was calculated as (\[frequency at baseline\] - \[frequency at 8 weeks\]) / (frequency at baseline). |
| Change on American Urological Association (AUA) Symptom Index | baseline to post-treatment (week 8) | Change in score on American Urological Association (AUA) Symptom Index (baseline to week 8). The index measures lower urinary tract symptoms. Scores range from 0 to 35, with higher scores indicating worse symptoms. |
| Patient Global Perception of Improvement (GPI) | post-treatment (week 8) | Patient global perception of improvement (much better to much worse) |
| Change in Nocturia Frequency | baseline to post-treatment (week 8) | Change in frequency of nocturia episodes based on 7-day bladder diary |
| Patient Global Rating of Activity Restriction | post-treatment (week 8) | Patient global rating of activity restriction (not at all to all the time) |
| Patient Report of Symptom Distress | post-treatment (week 8) | Patient report of how disturbed they were by symptoms (not at all to extremely) |
| Patient Global Rating of Bothersomeness of Side Effects | post-treatment (week 8) | Patient global rating of how bothersome their side effects were (no side effects to extremely bothersome) |
| Patient Desire for Alternate Treatment | post-treatment (week 8) | Patient response to Do you wish to receive another form of treatment? (yes) |
| Patient Satisfaction | post-treatment (week 8) | Patient global rating of satisfaction with progress in treatment (completely satisfied to very dissatisfied) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through mailed surveys about bladder symptoms and through clinics at two Veterans Affairs Medical Centers(2005-2009).
Pre-assignment details
To minimize possible effect of undetected obstruction we used a 4-week alpha-blocker run-in (tamsulosin 0.4 mg/d or alternative). Participants who continued to meet inclusion criteria after run-in were randomized. Alpha-blocker therapy was continued throughout the trial, unless not tolerated.
Participants by arm
| Arm | Count |
|---|---|
| Behavioral Training Delayed voiding, urge suppression techniques, pelvic floor muscle training | 73 |
| Drug Therapy Individually titrated, extended release oxybutynin chloride | 70 |
| Total | 143 |
Baseline characteristics
| Characteristic | Behavioral Training | Drug Therapy | Total |
|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 10.3 | 64.8 years STANDARD_DEVIATION 9.6 | 64.2 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 73 participants | 70 participants | 143 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 73 Participants | 70 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 73 | 0 / 70 |
| serious Total, serious adverse events | 0 / 73 | 0 / 70 |
Outcome results
Primary
24-hour Voiding Frequency
Mean voiding frequency per 24 hours derived from 7-day bladder dairy
Time frame: post-treatment (week 8)
Population: Treatment completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Training | 24-hour Voiding Frequency | 9.1 voids per 24-hour day | Standard Deviation 2.5 |
| Drug Therapy | 24-hour Voiding Frequency | 9.5 voids per 24-hour day | Standard Deviation 2.4 |
Comparison: The primary analysis was an equivalence analysis to compare the two treatment groups on posttreatment 24- hour voiding frequency using a margin of ±15% of the drug group mean. Schuirmann's two one-sided tests (TOST) approach was used first to examine completers and then repeated using last observation carried forward to include participants who did not complete therapy. Adjusting the test to regression, the analyses were repeated using baseline voiding frequency as a covariate.p-value: 0.001Regression, Linear
Secondary
Change in Nocturia Frequency
Change in frequency of nocturia episodes based on 7-day bladder diary
Time frame: baseline to post-treatment (week 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Training | Change in Nocturia Frequency | -0.70 nocturia episodes per night | Standard Deviation 0.72 |
| Drug Therapy | Change in Nocturia Frequency | -.32 nocturia episodes per night | Standard Deviation 1.28 |
Comparison: Standard regression methods adjusting for baseline valuesp-value: 0.05Regression, Linear
Secondary
Change in Urgency Severity
Indevus Urgency Severity Scale incorporated into the 7-day bladder diary. Scores for urgency severity ranged from 0 to 3: 0: None-no urgency 1. Mild-awareness of urgency, but is easily tolerated. 2. Moderate-enough urgency discomfort that it interferes with or shortens usual activity 3. Severe-extreme urgency discomfort that abruptly stops all activities or tasks.
Time frame: baseline to post-treatment (week 8)
Population: Participants who completed treatment and returned bladder diary with useable urgency scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Training | Change in Urgency Severity | .04 Score on scale | Standard Deviation 0.58 |
| Drug Therapy | Change in Urgency Severity | -.15 Score on scale | Standard Deviation 0.42 |
Comparison: Standard regression methods adjusting for baseline valuesp-value: 0.05t-test, 2 sided
Secondary
Change on American Urological Association (AUA) Symptom Index
Change in score on American Urological Association (AUA) Symptom Index (baseline to week 8). The index measures lower urinary tract symptoms. Scores range from 0 to 35, with higher scores indicating worse symptoms.
Time frame: baseline to post-treatment (week 8)
Population: Completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Training | Change on American Urological Association (AUA) Symptom Index | 3.4 Scores on the scale | Standard Deviation 4.6 |
| Drug Therapy | Change on American Urological Association (AUA) Symptom Index | 3.2 Scores on the scale | Standard Deviation 5.6 |
Comparison: Standard regression methods adjusting for baseline valuesp-value: 0.84t-test, 2 sided
Secondary
Patient Desire for Alternate Treatment
Patient response to Do you wish to receive another form of treatment? (yes)
Time frame: post-treatment (week 8)
Population: Completers minus one missing value
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Behavioral Training | Patient Desire for Alternate Treatment | 18 participants |
| Drug Therapy | Patient Desire for Alternate Treatment | 30 participants |
Comparison: Cochran Mantel-Haenszel procedure.p-value: 0.02Chi-squared
Secondary
Patient Global Perception of Improvement (GPI)
Patient global perception of improvement (much better to much worse)
Time frame: post-treatment (week 8)
Population: Completers minus one missing value
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Behavioral Training | Patient Global Perception of Improvement (GPI) | Much worse | 0 participants |
| Behavioral Training | Patient Global Perception of Improvement (GPI) | Much better | 23 participants |
| Behavioral Training | Patient Global Perception of Improvement (GPI) | Better | 30 participants |
| Behavioral Training | Patient Global Perception of Improvement (GPI) | About the same | 10 participants |
| Behavioral Training | Patient Global Perception of Improvement (GPI) | Worse | 0 participants |
| Drug Therapy | Patient Global Perception of Improvement (GPI) | Worse | 1 participants |
| Drug Therapy | Patient Global Perception of Improvement (GPI) | About the same | 7 participants |
| Drug Therapy | Patient Global Perception of Improvement (GPI) | Much better | 18 participants |
| Drug Therapy | Patient Global Perception of Improvement (GPI) | Much worse | 0 participants |
| Drug Therapy | Patient Global Perception of Improvement (GPI) | Better | 34 participants |
Comparison: Cochran Mantel-Haenszel procedure used to account for the ordinal nature of responses.p-value: 0.69Cochran-Mantel-Haenszel
Secondary
Patient Global Rating of Activity Restriction
Patient global rating of activity restriction (not at all to all the time)
Time frame: post-treatment (week 8)
Population: Com0leters minus one missing value
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Behavioral Training | Patient Global Rating of Activity Restriction | Some of the time | 11 participants |
| Behavioral Training | Patient Global Rating of Activity Restriction | Not at all | 29 participants |
| Behavioral Training | Patient Global Rating of Activity Restriction | All the time | 4 participants |
| Behavioral Training | Patient Global Rating of Activity Restriction | Slightly | 19 participants |
| Drug Therapy | Patient Global Rating of Activity Restriction | All the time | 1 participants |
| Drug Therapy | Patient Global Rating of Activity Restriction | Some of the time | 13 participants |
| Drug Therapy | Patient Global Rating of Activity Restriction | Slightly | 15 participants |
| Drug Therapy | Patient Global Rating of Activity Restriction | Not at all | 31 participants |
Comparison: Cochran Mantel-Haenszel procedure used to account for the ordinal nature of responses.p-value: 0.56Cochran-Mantel-Haenszel
Secondary
Patient Global Rating of Bothersomeness of Side Effects
Patient global rating of how bothersome their side effects were (no side effects to extremely bothersome)
Time frame: post-treatment (week 8)
Population: Completers minus one missing value
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Behavioral Training | Patient Global Rating of Bothersomeness of Side Effects | Not at all bothersome | 16 participants |
| Behavioral Training | Patient Global Rating of Bothersomeness of Side Effects | Somewhat | 7 participants |
| Behavioral Training | Patient Global Rating of Bothersomeness of Side Effects | A Little | 16 participants |
| Behavioral Training | Patient Global Rating of Bothersomeness of Side Effects | Extremely | 1 participants |
| Behavioral Training | Patient Global Rating of Bothersomeness of Side Effects | No side effects | 23 participants |
| Drug Therapy | Patient Global Rating of Bothersomeness of Side Effects | Extremely | 4 participants |
| Drug Therapy | Patient Global Rating of Bothersomeness of Side Effects | No side effects | 11 participants |
| Drug Therapy | Patient Global Rating of Bothersomeness of Side Effects | Not at all bothersome | 13 participants |
| Drug Therapy | Patient Global Rating of Bothersomeness of Side Effects | A Little | 19 participants |
| Drug Therapy | Patient Global Rating of Bothersomeness of Side Effects | Somewhat | 13 participants |
Comparison: Cochran Mantel-Haenszel procedure used to account for the ordinal nature of responses.p-value: 0.01Cochran-Mantel-Haenszel
Secondary
Patient Report of Symptom Distress
Patient report of how disturbed they were by symptoms (not at all to extremely)
Time frame: post-treatment (week 8)
Population: Completers minos one missing value
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Behavioral Training | Patient Report of Symptom Distress | Somewhat | 14 participants |
| Behavioral Training | Patient Report of Symptom Distress | Not at all | 19 participants |
| Behavioral Training | Patient Report of Symptom Distress | All the time | 0 participants |
| Behavioral Training | Patient Report of Symptom Distress | Slightly | 30 participants |
| Drug Therapy | Patient Report of Symptom Distress | All the time | 1 participants |
| Drug Therapy | Patient Report of Symptom Distress | Slightly | 35 participants |
| Drug Therapy | Patient Report of Symptom Distress | Not at all | 17 participants |
| Drug Therapy | Patient Report of Symptom Distress | Somewhat | 7 participants |
Comparison: Cochran Mantel-Haenszel procedure used to account for the ordinal nature of responses.p-value: 0.65Cochran-Mantel-Haenszel
Secondary
Patient Satisfaction
Patient global rating of satisfaction with progress in treatment (completely satisfied to very dissatisfied)
Time frame: post-treatment (week 8)
Population: Completers minus one missing value
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Behavioral Training | Patient Satisfaction | Completely satisfied | 36 participants |
| Behavioral Training | Patient Satisfaction | Somewhat satisfied | 25 participants |
| Behavioral Training | Patient Satisfaction | Somewhat dissatisfied | 2 participants |
| Behavioral Training | Patient Satisfaction | Very Dissatisfied | 0 participants |
| Drug Therapy | Patient Satisfaction | Very Dissatisfied | 0 participants |
| Drug Therapy | Patient Satisfaction | Completely satisfied | 25 participants |
| Drug Therapy | Patient Satisfaction | Somewhat dissatisfied | 2 participants |
| Drug Therapy | Patient Satisfaction | Somewhat satisfied | 33 participants |
Comparison: Cochran Mantel-Haenszel procedure used to account for the ordinal nature of responses.p-value: 0.16Cochran-Mantel-Haenszel
Secondary
Percent Change in Frequency of Urge Incontinence
Percent change in frequency of urge incontinence episodes based on 7-day bladder diary. Percent change was calculated as (\[frequency at baseline\] - \[frequency at 8 weeks\]) / (frequency at baseline).
Time frame: baseline to post-treatment (week 8)
Population: Included participants who experienced incontinence at baseline only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Training | Percent Change in Frequency of Urge Incontinence | 87.2 Percent change in episodes per week | Standard Deviation 0.25 |
| Drug Therapy | Percent Change in Frequency of Urge Incontinence | 75.6 Percent change in episodes per week | Standard Deviation 0.36 |
Comparison: Standard regression methods adjusting for baseline valuesp-value: 0.33t-test, 2 sided