Combined Behavioral and Drug Treatment of Overactive Bladder in Men

Overactive Bladder Clinical Trial

— COBALT  

Official title:

Combined Behavioral and Drug Treatment of Overactive Bladder in Men

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01175382
• Other study ID #: 1R01DK082548-01A1
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 3, 2010
• Last updated: August 26, 2015
• Start date: July 2010
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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. 201 men with OAB will be 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 432
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years and older

Eligibility

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 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lower Urinary Tract Symptoms
• Overactive Bladder
• Urinary Bladder, Overactive

Intervention

Behavioral:
• Behavioral training
Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, delayed voiding, and daily bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies.

Drug:
• Tolterodine + tamsulosin
Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Texas Health Science Center San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in frequency of urination	Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of urination	After 6-week intervention period (phase 1) and 12-week crossover (phase 2)	No
Secondary	Urgency	Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in urgency associated with each void and incontinent episode using the Indevus Urgency Severity Scale.	After 6-week intervention and 12-week crossover	No
Secondary	Urinary incontinence	Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in freqeuncy of incontinence episodes.	After 6-week intervention and 12-week crossover	No
Secondary	Nocturia	Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in frequency of nocturia.	After 6-week intervention and 12-week crossover	No
Secondary	Patient satisfaction	Patient global ratings of satisfaction using the validated Patient Satisfaction Question	After 6-week intervention and 12-week crossover	No
Secondary	Patient perceptions of improvement	Patient global ratings of improvement using the validated Estimated Percent Improvement and Global Perception of Improvement	After 6-week intervention and 12-week crossover	No
Secondary	Overactive Bladder Questionnaire (OAB-q)	Change from baseline on the OAB-q to measure symptom bother and condition-specific health-related quality of life	After 6-week intervention and 12-week crossover	No
Secondary	International Prostate Symptom Score (IPSS)	Change from baseline on the IPSS to measure urinary symptoms related to BPH	After 6-week intervention and 12-week crossover	No