Combined Behavioral and Drug Treatment of Overactive Bladder in Men

NCT01175382 | Completed Phase 2 Results DMC

• 1 other identifier: 1R01DK082548-01A1
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 3

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.

Conditions

Overactive Bladder; Lower Urinary Tract Symptoms

Keywords

Male Urogenital Diseases; Urinary Bladder, overactive; Behavioral Medicine; Drug Therapy

Outcome Measures

Primary Outcomes (3)

• Change in Frequency of Urination After 6-week Intervention (Last Observation Carried Forward)

  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)

  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)

  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 Outcomes (21)

• Change in Urgency From Baseline to 6 Weeks (Last Observation Carried Forward)

  From Baseline to 6 Weeks

• Change in Urinary Incontinence From Baseline to 6 Weeks (Last Observation Carried Forward)

  From Baseline to 6 Weeks

• Change in Nocturia From Baseline to 6 Weeks (Last Observation Carried Forward)

  From Baseline to 6 Weeks

• Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 6 Weeks (Last Observation Carried Forward)

  From Baseline to 6 Weeks

• Change in International Prostate Symptom Score (I-PSS) From Baseline to 6 Weeks. (Last Observation Carried Forward)

  From Baseline to 6 Weeks

Study Arms (3)

Behavioral Treatment alone

ACTIVE COMPARATOR

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

Drug Therapy (Tolterodine + tamsulosin)

ACTIVE COMPARATOR

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

Combined Behavioral + Drug Therapy

EXPERIMENTAL

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

Interventions

Behavioral training BEHAVIORAL

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.

Also known as: Urge suppression, Delayed voiding, Pelvic floor muscle training

Behavioral Treatment alone

Tolterodine + tamsulosin DRUG

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

Also known as: Flomax, Detrol Long-Acting (LA), Tolterodine tartrate

Drug Therapy (Tolterodine + tamsulosin)

Combined Behavioral + Drug Therapy OTHER

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).

Combined Behavioral + Drug Therapy

Eligibility Criteria

• Age: 40 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Urinary flow rate \< 8.0 mL/sec on a void greater than 125 ml.
• Post-void residual volume greater than 150 mL (based on bladder ultrasound after voiding in the presence of a normal urge to urinate).
• 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.
• Transurethral resection of the prostate (TURP), simple prostatectomy, or other benign prostatic hypertrophy (BPH) related surgery within the past 5 years.
• Current active treatment for prostate cancer.
• History of radical prostatectomy.
• Previous artificial urinary sphincter, sling procedure, bladder-injection of botulinum toxin, or implanted sacral neuromodulation device.
• 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.
• 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.
• 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).
• Neurologic conditions such as Parkinson's, spinal cord injury, multiple sclerosis, or myasthenia gravis.
• Impaired mental status. Patients who screen as probable dementia on the Mini-Cog.
• 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.
• Hypersensitivity to tolterodine or tamsulosin.
• Current use of an alpha blocker agent. Evaluation will be delayed until the drug has been discontinued for 2 weeks.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Emory University

Atlanta, Georgia, 30033, United States

Location

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Funada S, Yoshioka T, Luo Y, Sato A, Akamatsu S, Watanabe N. Bladder training for treating overactive bladder in adults. Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD013571. doi: 10.1002/14651858.CD013571.pub2.

  PMID: 37811598 DERIVED

• 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.

  PMID: 31930360 DERIVED

MeSH Terms

Conditions

Urinary Bladder, Overactive; Lower Urinary Tract Symptoms; Male Urogenital Diseases

Interventions

Tolterodine Tartrate; Tamsulosin; Drug Therapy

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols; Benzenesulfonamides; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Therapeutics

Limitations and Caveats

No limitations or caveats for this trial

Results Point of Contact

• Title: Dr. Kathryn Burgio
• Organization: University of Alabama at Birmingham

kburgio@uabmc.edu

205-558-7064

Study Officials

• Kathryn L Burgio, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 4, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: May 25, 2017
• Results First Posted: May 25, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)