Effect of Dutasteride on Bladder Wall Hypertrophy in Patients With Benign Prostatic Obstruction

Effect of Dutasteride on Bladder Wall Hypertrophy in Patients With Benign Prostatic Obstruction: A 24-Week Open-Label, Single-Arm Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Drug: Dutasteride

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age≥50 and <80 years old
2. Presence of LUTS for at least 3 months
3. IPSS≥15
4. Bladder outlet obstruction confirmed by pressure-flow study (BOOI > 20)
5. Prostate volume measured by TRUS ≥ 30ml and < 100ml
6. Able to comply with the prescribed treatment protocol and evaluations.

Exclusion Criteria:

1. Patients with neurogenic voiding disorders
2. Patients with prostate or bladder cancer
3. Patients underwent urethral, prostate or bladder neck surgery
4. Patients with urethral stricture or bladder neck contracture
5. Serum PSA≥4ng/ml (if the patient confirmed as no malignancy by prostate biopsy can be included).
6. Patients who medicated with 5ARI within 6 months
7. Patients who do not agree with the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dutasteride	Drug: Dutasteride; Dutasteride 0.5 mg od.; Other Names: Avodart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent (numeric) changes in ultrasound-estimated bladder weight (UEBW)	Baseline and 6 months of dutasteride treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Urodynamic parameters	Baseline and 3 and/or 6 months of dutasteride treatment
Micturition diary efficacy parameters	Baseline and 3 and/or 6 months of dutasteride treatment
Prostate volume parameters	Baseline and 3 and/or 6 months of dutasteride treatment
Quality of life parameters	Baseline and 3 and/or 6 months of dutasteride treatment
LUTS Symptom parameters	Baseline and 3 and/or 6 months of dutasteride treatment
LUTS outcome score	Baseline and 3 and/or 6 months of dutasteride treatment
Patient perceptions	Baseline and 3 and/or 6 months of dutasteride treatment
Safety parameters	Baseline and 3 and/or 6 months of dutasteride treatment

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 22, 2009
• First Submitted That Met QC Criteria: January 22, 2009
• First Posted (Estimate): January 23, 2009

Study Record Updates

• Last Update Posted (Estimate): June 11, 2009
• Last Update Submitted That Met QC Criteria: June 8, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Pathological Conditions, Anatomical; Prostatic Hyperplasia; Hyperplasia; Hypertrophy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; 5-alpha Reductase Inhibitors; Dutasteride
• Other Study ID Numbers: 2006-06-022