Effect of Dutasteride on Bladder Wall Hypertrophy in Patients With Benign Prostatic Obstruction
Condition: Benign Prostatic Hyperplasia
MeSH terms: Prostatic Hyperplasia; Hyperplasia; Hypertrophy
Study type: Interventional
Phase: Phase 4

Summary: 
      Increased bladder mass occurs as a consequence of bladder outlet obstruction in animals and
      patients, and relief of bladder outlet obstruction reverses an increased bladder mass.
      Whether increased bladder mass is not only a consequence of bladder outlet obstruction but
      also a relevant risk factor for the progression of lower urinary tract symptoms associated
      with benign prostate hyperplasia cannot be decided due to a lack of appropriate data, most
      likely because bladder wall thickness is not routinely measured in clinical studies and/or
      routine clinical practice. Despite this lack of data, many urologists feel that increased
      bladder mass should be prevented or decreased to reduce the occurrence of serious
      complications.

      The possibility of using bladder wall thickness data as criteria for benign prostate
      hyperplasia intervention and as outcome criteria for benign prostate hyperplasia treatment
      has been proposed. Detrusor hypertrophy associated with bladder outlet obstruction can be
      imaged on suprapubic ultrasound, and bladder mass can be quantified from the evaluation of
      bladder wall thickness and bladder volume. Bladder wall hypertrophy has been found to be
      correlated with detrusor function.

      Independent studies have shown that surgical treatment of benign prostatic obstruction
      results in a significant decrease of bladder mass. Preliminary data suggest the possibility
      that medical treatment with alpha-adrenergic antagonists might also produce a reduction of
      bladder wall hypertrophy.

      The investigators assume that the prevention of benign prostate hyperplasia progression by
      alpha-adrenergic antagonists and 5 alpha reductase inhibitors may be result of bladder
      function protection. To our knowledge there have been no studies that evaluated the effects
      of a 5 alpha reductase inhibitors on bladder function. Therefore, the investigators plan to
      conduct a prospective trial evaluating the effects of 5 alpha reductase inhibitors on bladder
      function by the evaluation of bladder wall thickness and lower urinary tract symptoms.
    

Detailed description: 
      1 Objective

      1.1 Primary Objective: To explore the efficacy of Dutasteride in reducing bladder wall
      hypertrophy from baseline to 6 months of treatment in male patients with benign prostatic
      obstruction.

      1.2 Secondary Objective:

        1. To explore the efficacy of Dutasteride in reducing the LUTS symptoms, number of
           micturitions, and number of urgency episodes from baseline to 6 months of treatment

        2. To explore the efficacy of Dutasteride on the urodynamic parameters from baseline to 6
           months of treatment.

        3. To explore the efficacy of Dutasteride on the tolerability, safety, patient perception
           and quality of life from baseline to 6 months of treatment.

      2 Endpoints

      2.1 Primary Endpoint: Percent (numeric) changes in ultrasound-estimated bladder weight (UEBW)
      from baseline to 6 months of treatment

      2.2 Secondary Endpoint:

      Urodynamic parameters: From baseline to 6 months of treatment

      • Percentage and numeric changes of the

        -  Maximum flow rate (mL/s)

        -  Average flow rate (mL/s)

        -  Post-void residual urine volume (mL)

      Micturition diary efficacy parameters: From baseline to 6 months of treatment

        -  Percentage and numeric changes in micturition frequency/24 hours

        -  Percentage and numeric changes in mean volume voided per micturition

        -  Percentage and numeric changes in mean number and severity of urgency per micturition

      Prostate volume parameters:

      • Change in prostate volume by TRUS from baseline to after 6 months of treatment.

      • Change in serum PSA from baseline to after 6 months of treatment.

      Quality of life parameters:

      • Change in Bother Score of IPSS score from baseline to 6 months of treatment

      LUTS Symptom parameters:

      • Change in IPSS score from baseline to 6 months of treatment

      - total score: sum of all 7 questions

        -  storage score: sum of questions 2, 4 and 7

        -  voiding score: sum of questions 1, 3, 5 and 6

      LUTS outcome score (LOS)

      • Change in LOS from baseline to 6 months of treatment

      Patient perceptions:

        -  Patient perception of treatment benefit after 3 and 6 months of treatment

        -  Change in patient perception of urgency from baseline to 3 and 6 month of treatment

      Safety parameters:

      • Incidence and severity of adverse events

      • Incidence and reason of withdrawals

      3. STUDY DESIGN AND METHODS

      Study Design: This is a 6-month prospective Phase IV study to explore the effect on the
      bladder function of Dutasteride in male patients with benign prostatic obstruction.
    

Intervention name(s): Dutasteride
Intervention type(s): Drug
Intervention description(s): Dutasteride 0.5 mg od.
Other intervention name(s): Avodart
Intervention MeSH terms: Dutasteride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment