Clinical trial NCT01175382: Combined Behavioral and Drug Treatment of Overactive Bladder in Men
Official title: Combined Behavioral and Drug Treatment of Overactive Bladder in Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Overactive Bladder
Lower Urinary Tract Symptoms
Keywords: Male Urogenital Diseases
Urinary Bladder, overactive
Behavioral Medicine
Drug Therapy
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2010-08-04
Enrollment: 204
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The design of this study is a 3 group randomized trial. Group 1 was randomized to drug only for the first 6 weeks, followed by a step up to drug plus behavior from 6 weeks to 12 weeks. Group 2 was randomized to behavior only for the first 6 weeks, followed by a step up to behavior plus drug from 6 weeks to 12 weeks. Group 3 was randomized to behavior plus drug from baseline to 12 weeks.
Primary purpose: TREATMENT

Brief summary: The primary aim of this project is to evaluate the effectiveness of combined behavioral + drug therapy compared to behavioral treatment alone and drug therapy alone as a way to improve outcomes in the treatment of OAB symptoms in men. We hypothesize that combined therapy will result in better outcomes than either behavioral or drug therapy alone. The second aim is to compare two methods of implementing combined therapy: simultaneously as initial therapy vs. stepped therapy, in which therapies are combined following initial behavioral or drug therapy alone. The third aim is to examine the costs and cost-effectiveness of combined behavioral + drug therapy compared to behavioral or drug therapy alone.

Detailed description: Overactive bladder (OAB) is a very common, distressing condition that manifests as bothersome symptoms of urgency, frequent urination, urge incontinence, and nocturia, and impacts the lives of millions of men. OAB symptoms are most often treated with pharmacologic therapies (alpha-blocking agents and/or antimuscarinic agents) or behavioral treatments. Although drug therapies (even combined drug therapies) and behavioral treatments reduce OAB symptoms, few patients are completely cured with either treatment alone. Therefore, there is a need to improve interventions for this common problem. The primary purpose of this study is to test the effectiveness of combining behavioral treatment and drug therapy as a way to improve outcomes in the treatment of OAB symptoms in men. This is a 3-site, 2-stage, 3-arm randomized clinical trial of behavioral treatment, drug therapy, and combined drug + behavioral therapy for men with OAB, to examine the efficacy of combined therapy and whether it yields higher success rates than either therapy alone. 204 men with OAB were enrolled and randomized to 1) drug therapy alone followed by combined therapy, 2) behavioral treatment alone followed by combined therapy, or 3) combined therapy as initial treatment.

Eligibility criteria: Inclusion Criteria:

1. Community-dwelling men
2. Age 40 years or older
3. Patient-reported urgency and 9.0 or more voids per 24-hour day (on average) on the 7-day baseline bladder diary.

Exclusion Criteria:

1. Urinary flow rate \< 8.0 mL/sec on a void greater than 125 ml.
2. Post-void residual volume greater than 150 mL (based on bladder ultrasound after voiding in the presence of a normal urge to urinate).
3. Urinary tract infection (defined as growth of greater than 10,000 colonies per ml of a urinary pathogen on urine culture). Patients will be referred for treatment with antibiotics and may be enrolled if OAB symptoms persist after the infection is resolved.
4. Transurethral resection of the prostate (TURP), simple prostatectomy, or other benign prostatic hypertrophy (BPH) related surgery within the past 5 years.
5. Current active treatment for prostate cancer.
6. History of radical prostatectomy.
7. Previous artificial urinary sphincter, sling procedure, bladder-injection of botulinum toxin, or implanted sacral neuromodulation device.
8. Poorly controlled diabetes (glycosylated hemoglobin \>9.0 within last 3 months). Subjects with poorly controlled diabetes will be offered enrollment if the OAB symptoms persist after the diabetes is controlled appropriately.
9. Hematuria on microscopic examination in the absence of infection. A urologic consultation will be recommended and enrollment will depend on clearance by a urologist and agreement by the Site PI that entry into the treatment protocol is not contraindicated.
10. Any unstable medical condition (particularly: cancers under active treatment, decompensated congestive heart failure, history of malignant arrhythmias, unstable angina, diagnosed by history or physical exam).
11. Neurologic conditions such as Parkinson's, spinal cord injury, multiple sclerosis, or myasthenia gravis.
12. Impaired mental status. Patients who screen as probable dementia on the Mini-Cog.
13. Contraindications to the study drugs (tolterodine and tamsulosin) including history of postural hypotension with syncope, history of acute urinary retention requiring catheterization, narrow angle glaucoma, or history of gastric retention.
14. Hypersensitivity to tolterodine or tamsulosin.
15. Current use of an alpha blocker agent. Evaluation will be delayed until the drug has been discontinued for 2 weeks.
16. Current use of an anti-muscarinic agent for OAB. Evaluation will be delayed until the drug has been discontinued for 2 weeks.
17. If on a diuretic, dose has not been stable for at least 4 weeks.
18. If taking dutasteride or finasteride, dose has not been stable for at least 6 months.
19. If on an antibiotic for prostatitis. Patients will be offered re-evaluation if OAB symptoms persist when antibiotics are completed.
20. Full course of behavioral training.

Primary outcomes:
measure: Change in Frequency of Urination After 6-week Intervention (Last Observation Carried Forward)
timeFrame: From Baseline to 6 Weeks
measure: Change in Frequency of Urination From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
timeFrame: Change from 6 weeks to 12 weeks
measure: Change in Frequency of Urination From Baseline to 12 Weeks (Last Observation Carried Forward)
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Change in Urgency From Baseline to 6 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 6 Weeks
measure: Change in Urinary Incontinence From Baseline to 6 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 6 Weeks
measure: Change in Nocturia From Baseline to 6 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 6 Weeks
measure: Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 6 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 6 Weeks
measure: Change in International Prostate Symptom Score (I-PSS) From Baseline to 6 Weeks. (Last Observation Carried Forward)
timeFrame: From Baseline to 6 Weeks
measure: Patient Satisfaction
timeFrame: From Baseline to 6 Weeks
measure: Patient Perceptions of Improvement
timeFrame: From Baseline to 6 Weeks
measure: How Bothersome Were Side Effects? 6 Week Report
timeFrame: From Baseline to 6 weeks
measure: Change in Urgency Score From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
timeFrame: Change from 6 weeks to 12 weeks
measure: Change in Urinary Incontinence From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
timeFrame: Change from 6 weeks to 12 weeks
measure: Change in Nocturia From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
timeFrame: Change from 6 weeks to 12 weeks
measure: Change in Overactive Bladder Questionnaire (OAB-q) From 6 to 12 Weeks (Last Observation Carried Forward)
timeFrame: Change from 6 week to 12 weeks
measure: Change in International Prostate Symptom Score (IPSS) From 6 to 12 Weeks (Last Observation Carried Forward)
timeFrame: Change from 6 weeks to 12 weeks
measure: Patient Perception of Improvement at 12 Weeks
timeFrame: 12 weeks post randomization
measure: Satisfaction With Progress at 12 Weeks
timeFrame: 12 weeks post randomization
measure: How Bothersome Were Side Effects? 12 Week Report
timeFrame: 12 weeks post randomization
measure: Change in Nocturia Measured From Baseline to 12 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 12 weeks
measure: Change in Urgency Score From Baseline to 12 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 12 weeks
measure: Change in Urinary Incontinence Episodes From Baseline to 12 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 12 weeks
measure: Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 12 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 12 weeks
measure: Change in International Prostate Symptom Score (I-PSS) From Baseline to 12 Weeks (Last Observation Carried Forward)
timeFrame: From Baseline to 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
Study officials:
affiliation: University of Alabama at Birmingham
name: Kathryn L Burgio, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burgio KL, Kraus SR, Johnson TM 2nd, Markland AD, Vaughan CP, Li P, Redden DT, Goode PS. Effectiveness of Combined Behavioral and Drug Therapy for Overactive Bladder Symptoms in Men: A Randomized Clinical Trial. JAMA Intern Med. 2020 Mar 1;180(3):411-419. doi: 10.1001/jamainternmed.2019.6398.