Official Title: “A Pilot Study to Measure the Efficacy and Safety of Long-Acting Tolterodine (Detrol LA) on Continued Detrusor Overactivity in Patients That Have Undergone Treatment for Bladder Outlet Obstruction”

The subjects who have symptoms of overactive bladder (many trips to the bathroom, and urgency with or without the inability to hold your urine until you get to the toilet) are invited to participate in this research study. Overactive bladder is a common sequelae of long-term bladder outlet obstruction in men. Unfortunately, it does not often resolve after treatment of the obstruction (transurethral resection of the prostate). These patients are usually started empirically on alpha-blockers or occasionally anticholinergic agents, former used to treat enlarged prostate medically, and latter, to treat overactive bladder. The investigators hypothesize that these patients would be significantly improved with a long-acting anticholinergic agent such as Detrol LA (tolterodine).

Earlier studies have shown that anticholinergic drugs seem to have a beneficial effect on symptoms of patients with bladder outlet obstruction and overactive bladder. In addition, anticholinergic drug tolterodine is not associated with increased incidence of complication like acute urinary retention, a state where patient is unable to empty the bladder as an adverse effect of the drug.

A large proportion of our patients that are undergoing treatment for bladder outlet obstruction also have overactive bladder. The investigators propose a double blind, randomized, placebo-controlled trial to evaluate the efficacy of Detrol LA 4mg, an anticholinergic in patients that have continued symptoms of overactive bladder one month following transurethral resection of the prostate. Patients with overactive bladder on urodynamic test preoperatively will be considered. If these patients continue to have symptoms at the one-month post-operative visit, they will be enrolled into the study. The investigators expect a total of 50 patients to be enrolled within 4 months. One arm will receive placebo, the other will receive Detrol LA 4 mg. The patients will be followed at 3 months post-op, 4 months post-op, and 7 months post-op. At each post-op visit, the patients will fill out an American Urological Association (AUA) symptom score questionnaire, have noninvasive uroflowmetry performed, and have a post-void residual measured by bladder scan.

Using standard statistical analysis, the investigators will see if there is a difference in symptoms, post-void residual, or maximum flow rate between the two arms at 6 months. The investigators will continue in an open-label manner after six months. If the Detrol LA arm has better outcomes, the investigators will offer the placebo group Detrol LA 4mg at the six month period and continue the study to evaluate long-term efficacy, dropout rate, and complications. No dosing adjustments will be allowed for the duration of the study.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: August 2009

Intervention(s) in this Clinical Trial

• Drug: Detrol LA (Tolterodine)
  • 4mg by mouth once daily
• Drug: Placebo
  • One tablet by mouth once daily

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: I
  • Detrol LA 4mg (tolterodine)
• Placebo Comparator: II
  • Placebo

Primary Measures

• AUA symptom score
  • Time Frame: screening, 2, 3, 6 months
    Safety Issue?: No

Secondary Measures

• Uroflowmetry and post-void residual
  • Time Frame: screening, 2, 3, 6 months
    Safety Issue?: No

Inclusion Criteria:

• Male greater than or equal to 40 years of age.
• Clinical signs and symptoms of frequency and urgency, enlarged prostate, and urodynamic study consistent with overactive bladder.
• IPSS greater than 12, with IPSS QoL greater than 3 at screening visit.
• Ability and willingness to correctly complete the micturition diary and all the trial related questionnaires comply with scheduled visits and comply with trial procedures.
• Capability of understanding and having signed the informed consent form after full discussion of the research, nature of the treatment, and its risks and benefits.
• Procedure to treat BOO by TURP or PVP greater than 1 month ago.

Exclusion Criteria:

• A known history of interstitial cystitis, uninvestigated hematuria, or bladder outlet obstruction due to : vesical neck contracture, clinical suspicion of prostate carcinoma, mullerian duct cysts, urethral obstruction due to stricture/valves/sclerosis of urethral tumor, radiation cystitis, genitourinary tuberculosis, bladder calculi, or detrusor-sphincter dyssynergia.
• Evidence of Urinary Tract Infection according to local standard of care.
• Expectation of initiating treatment during the duration of this study with - any drug treatment for OAB, any drugs with significant anticholinergic, antispasmodic, parasympathetic, or cholinergic agonistic effects, any drug treatment for BPH.
• Use of any electrostimulation within the 30 days before randomization, or the expectation to initiate such therapy during the study.
• History of prostate cancer.
• A serum prostate-specific antigen concentration of greater than10ng/mL. Men with serum
• PSA concentrations of greater than 10ng/mL have to have prostate cancer excluded according to the local standard of care.
• Any condition which, in the opinion of the investigator, makes the patient unstable, or with contraindications for inclusion, e.g., uncontrolled narrow-angled glaucoma, urinary retention, preplanned prostate surgery, or gastric retention.
• Significant hepatic or renal disease, defined as twice the upper limit of the reference ranges regarding serum concentrations of AST, ALT, ALP, urea nitrogen, or creatinine.
• Use of any other investigational drug in the 2 months preceding visit 1.
• History of postural hypotension or syncope in the judgement of the investigator based on local standards of care.
• Alcohol and/or any other drug abuse in the opinion of the investigator.
• Medications such as erythromycin, Biaxin (clarithromycin), Sporanox (itraconazole), Nizoral (ketoconazole), Neoral and Sandimmune (cyclosporine), Velban (vinblastine), and miconazole.
• Non-medication treatments such as bio-feedback or other bladder training exercises.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Weill Medical College of Cornell University

Overall Clinical Trial Officials and Contacts

Alexis Te, MD Principal Investigator Cornell University  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00605319

Study ID Number: 0506007934

ClinicalTrials.gov Identifier: NCT00605319

Health Authority: United States: Institutional Review Board