Combined Behavioral and Drug Treatment of Overactive Bladder in Men (COBALT)

The University of Alabama at Birmingham

Status and phase: Completed; Phase 3; Phase 2

Conditions: Lower Urinary Tract Symptoms; Overactive Bladder

Treatments: Behavioral: Behavioral training; Drug: Tolterodine + tamsulosin; Other: Combined Behavioral + Drug Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01175382

1R01DK082548-01A1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 204 patients

Sex: Male

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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204 participants in 3 patient groups

Behavioral Treatment alone

Active Comparator group

Description:

Behavioral treatment is implemented in 4 clinic visits over a period of 6 weeks, followed by 6 weeks of combined behavioral + drug therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and daily bladder diaries, 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.

Treatment:

Behavioral: Behavioral training

Drug Therapy (Tolterodine + tamsulosin)

Active Comparator group

Description:

Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).

Treatment:

Drug: Tolterodine + tamsulosin

Combined Behavioral + Drug Therapy

Experimental group

Description:

Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).

Treatment:

Other: Combined Behavioral + Drug Therapy