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

April 17, 2017 updated by: Kathryn Burgio, University of Alabama at Birmingham
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
204

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Georgia
      • Atlanta, Georgia, United States, 30033
        • Emory University
    • Texas
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Behavioral Treatment alone
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.
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.
Other Names:
  • Pelvic floor muscle training
  • Urge suppression
  • Delayed voiding
Active Comparator: Drug Therapy (Tolterodine + tamsulosin)
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).
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).
Other Names:
  • Flomax
  • Tolterodine tartrate
  • Detrol Long-Acting (LA)
Experimental: Combined Behavioral + Drug Therapy
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).
Other: Combined Behavioral + Drug Therapy
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Frequency of Urination After 6-week Intervention (Last Observation Carried Forward)
Time Frame: From Baseline to 6 Weeks
Bladder diaries completed by subjects prior to randomization and following the first phase of treatment was used to calculate changes in frequency of urination.
From Baseline to 6 Weeks
Change in Frequency of Urination From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
Time Frame: Change from 6 weeks to 12 weeks
Bladder diaries completed by subjects prior to randomization and following each phase of treatment were used to calculate changes in frequency of urination.
Change from 6 weeks to 12 weeks
Change in Frequency of Urination From Baseline to 12 Weeks (Last Observation Carried Forward)
Time Frame: Baseline to 12 weeks
Bladder diaries completed by subjects prior to randomization and following the second phase of treatment were used to calculate changes in frequency of urination
Baseline to 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Urgency From Baseline to 6 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 6 Weeks
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 (IUSS). IUSS asks patients about the degree of urgency, as meant to describe the urge to urinate. Patients are asked to rate the degree of urgency and its impact on the completion of activity or tasks during the time that the urgency sensation is present and before reaching the toilet for a toilet void. Four distinct, subjective degrees of urgency severity were identified, including 1) no sensation of urgency, 2) awareness of urgency but easily tolerated, 3) urgency that is somewhat uncomfortable and 4) extreme urgency discomfort.
From Baseline to 6 Weeks
Change in Urinary Incontinence From Baseline to 6 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 6 Weeks
Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in frequency of incontinence episodes.
From Baseline to 6 Weeks
Change in Nocturia From Baseline to 6 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 6 Weeks
Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in frequency of nocturia.
From Baseline to 6 Weeks
Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 6 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 6 Weeks
Change from baseline on the OAB-q to measure symptom bother and condition-specific health-related quality of life. This questionnaire asks about how much you have been bothered by selected bladder symptoms during the past 4 weeks. Scale ranges from 8 to 48 with higher scores indicating a greater degree of bother.
From Baseline to 6 Weeks
Change in International Prostate Symptom Score (I-PSS) From Baseline to 6 Weeks. (Last Observation Carried Forward)
Time Frame: From Baseline to 6 Weeks
Change from baseline to 6 weeks on the International Prostate Symptom Score (IPSS) to measure urinary symptoms related to benign prostatic hypertrophy (BPH). The I-PSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).
From Baseline to 6 Weeks
Patient Satisfaction
Time Frame: From Baseline to 6 Weeks
Patient global ratings of satisfaction using the validated Patient Satisfaction Question
From Baseline to 6 Weeks
Patient Perceptions of Improvement
Time Frame: From Baseline to 6 Weeks
Patient global ratings of improvement using the validated Estimated Percent Improvement and Global Perception of Improvement
From Baseline to 6 Weeks
How Bothersome Were Side Effects? 6 Week Report
Time Frame: From Baseline to 6 weeks
Ordinal Rating regarding how bothersome side effects were
From Baseline to 6 weeks
Change in Urgency Score From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
Time Frame: Change from 6 weeks to 12 weeks
Bladder diaries completed by subjects 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 (IUSS). IUSS asks patients about the degree of urgency, as meant to describe the urge to urinate. Patients are asked to rate the degree of urgency and its impact on the completion of activity or tasks during the time that the urgency sensation is present and before reaching the toilet for a toilet void. Four distinct, subjective degrees of urgency severity were identified, including 1) no sensation of urgency, 2) awareness of urgency but easily tolerated, 3) urgency that is somewhat uncomfortable and 4) extreme urgency discomfort.
Change from 6 weeks to 12 weeks
Change in Urinary Incontinence From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
Time Frame: Change from 6 weeks to 12 weeks
Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of incontinence episodes.
Change from 6 weeks to 12 weeks
Change in Nocturia From 6 Weeks to 12 Weeks (Last Observation Carried Forward)
Time Frame: Change from 6 weeks to 12 weeks
Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of nocturia
Change from 6 weeks to 12 weeks
Change in Overactive Bladder Questionnaire (OAB-q) From 6 to 12 Weeks (Last Observation Carried Forward)
Time Frame: Change from 6 week to 12 weeks
Change from 6 weeks to 12 weeks on the OAB-q to measure symptom bother and condition-specific health-related quality of life. This questionnaire asks about how much you have been bothered by selected bladder symptoms during the past 4 weeks. Scale ranges from 8 to 48 with higher scores indicating a greater degree of bother.
Change from 6 week to 12 weeks
Change in International Prostate Symptom Score (IPSS) From 6 to 12 Weeks (Last Observation Carried Forward)
Time Frame: Change from 6 weeks to 12 weeks
Change from 6 weeks to 12 weeks on the International Prostate Symptom Score (IPSS) to measure urinary symptoms related to BPH.The I-PSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).
Change from 6 weeks to 12 weeks
Patient Perception of Improvement at 12 Weeks
Time Frame: 12 weeks post randomization
Patient global ratings of improvement using the validated Estimated Percent Improvement and Global Perception of Improvement.
12 weeks post randomization
Satisfaction With Progress at 12 Weeks
Time Frame: 12 weeks post randomization
Patient global ratings of satisfaction using the validated Patient Satisfaction Question.
12 weeks post randomization
How Bothersome Were Side Effects? 12 Week Report
Time Frame: 12 weeks post randomization
Ordinal Rating regarding how bothersome side effects were
12 weeks post randomization
Change in Nocturia Measured From Baseline to 12 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 12 weeks
Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in the frequency nocturia
From Baseline to 12 weeks
Change in Urgency Score From Baseline to 12 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 12 weeks
Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of urgency associated with each void and incontinent episode using the Indevus Urgency Severity Scale (IUSS). IUSS asks patients about the degree of urgency, as meant to describe the urge to urinate. Patients are asked to rate the degree of urgency and its impact on the completion of activity or tasks during the time that the urgency sensation is present and before reaching the toilet for a toilet void. Four distinct, subjective degrees of urgency severity were identified, including 1) no sensation of urgency, 2) awareness of urgency but easily tolerated, 3) urgency that is somewhat uncomfortable and 4) extreme urgency discomfort.
From Baseline to 12 weeks
Change in Urinary Incontinence Episodes From Baseline to 12 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 12 weeks
Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of urination
From Baseline to 12 weeks
Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 12 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 12 weeks
Change from baseline to 12 weeks on the OAB-q to measure symptom bother and condition-specific health-related quality of life. This questionnaire asks about how much you have been bothered by selected bladder symptoms during the past 4 weeks. Scale ranges from 8 to 48 with higher scores indicating a greater degree of bother.
From Baseline to 12 weeks
Change in International Prostate Symptom Score (I-PSS) From Baseline to 12 Weeks (Last Observation Carried Forward)
Time Frame: From Baseline to 12 weeks
Change from Baseline to 12 weeks on the International Prostate Symptom Score (I-PSS) to measure urinary symptoms related to BPH. The I-PSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).
From Baseline to 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Alabama at Birmingham

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kathryn L Burgio, PhD, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 25, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1R01DK082548-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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