Effect of 12 Weeks Treatment With Tadalafil vs Placebo on Lower Urinary Tract Symptoms

Sponsor

University of Florence (Other)

Overall Status

Completed

CT.gov ID

NCT02252367

Collaborator

Eli Lilly and Company (Industry)

Enrollment

Location

Arms

Actual Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

At present time several preclinical and clinical study have demonstrated the safety and efficacy of PDE5 (phosphodiesterase type 5)-inhibitors for LUTS/BPH (lower urinary tract symptoms/benign prostatic hyperplasia) patients with or without erectile dysfunction. However, the link between clinical outcomes (symptoms scores), functional activity (urodynamic findings) and molecular pathways, in particular regarding inflammatory pattern (molecular analyses), has not been previously investigated.

Aim of present study is to assess, for the first time in literature, changes in pressure flow study (PFS) and changes in molecular profile of prostatic tissue (inflammatory and tissue remodeling markers) in men treated for 12 weeks with tadalafil 5 mg compared with placebo and to correlate these data with changes in symptoms scores (IPSS, International Prostatic Symptoms Score) in men with LUTS secondary to BPH refractory to alpha blockers.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia Lower Urinary Tract Symptoms	Drug: Tadalafil Other: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Double-blind, Placebo-controlled Study on Men With Lower Urinary Tract Symptoms to Assess Changes in Pressure Flow Study and in Molecular Profile of Prostatic Tissue After 12 Weeks Treatment With Tadalafil.

Actual Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Jan 1, 2019

Actual Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tadalafil 43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to tadalafil 5 mg - 1 film-coated tablet orally once daily for 12 weeks.	Drug: Tadalafil Tadalafil 5 mg once daily for 12 weeks. Other Names: Cialis
Placebo Comparator: Placebo 43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to placebo.	Other: Placebo Placebo tablet once daily for 12 weeks.

Arm

Intervention/Treatment

Experimental: Tadalafil

43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to tadalafil 5 mg - 1 film-coated tablet orally once daily for 12 weeks.

Drug: Tadalafil

Tadalafil 5 mg once daily for 12 weeks.

Other Names:

Cialis

Placebo Comparator: Placebo

43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to placebo.

Other: Placebo

Placebo tablet once daily for 12 weeks.

Outcome Measures

Primary Outcome Measures

Improvement of LUTS/BPH symptoms [12 weeks]
BPH-associated inflammatory symptoms will be assessed by using the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI). BPH-associated LUTS will be assessed by using International Prostate Symptom Score (IPSS).

Secondary Outcome Measures

Improvement of pressure flow study (PFS) parameters [12 weeks]
Maximum flow rate (Qmax), average flow rate (Qave), voided volume (Vcomp), post void residual volume (PVR) will be evaluated. An abdominal ultrasound immediately after voiding for uroflowmetry will be performed in order to determine the PVR.
Volumetric change of the prostate [12 weeks]
Prostate volume as assessed by transrectal ultrasound
Change in prostate inhomogeneity and in the number of prostatic macrocalcifications [12 weeks]
BPH-associated prostate inhomogeneity and presence of micro-calcifications will be assessed by using male genital tract male genital tract colour-Doppler ultrasonography.
Variation in genic expression of prostatic inflammation markers [12 weeks]
BPH-associated prostate inflammation, fibrosis, and hypoxia will be measured by immunohistochemical and quantitative RT-PCR (qRT-PCR) analyses of inflammatory-, fibrosis- and hypoxia-related markers.
Variation in serum inflammation markers CRP (C-reactive protein) and ESR (Erythrocyte Sedimentation Rate) [12 weeks]
CRP measured on serum and ESR measured on blood drawn at baseline and after 12 weeks
Improvement in metabolic profile [12 weeks]
Metabolic parameters will be evaluated (glycaemia, insulinemia, total cholesterol, HDL, triglycerides, HbA1c, mean arterial pressure, waist circumference, body mass index)
Variation in seminal plasma IL-8 (interleukin-8) levels [12 weeks]
Seminal IL-8, a chemokine involved in male genital tract infection/inflammation, will be evaluated.
Improvement in erectile function [12 weeks]
Erectile function will be assessed by using the International Index of Erectile Function-5 (IIEF-5) score.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

adult male subjects planned to undergo simple prostatectomy (TURP, Transurethral resection of the prostate, or open prostatectomy) for benign prostatic hyperplasia;
treatment with alpha-blockers (Tamsulosin 0.4 mg/die)
being capable of giving informed consent.

Exclusion Criteria:

participation in another clinical study;
known or suspected presence of prostatic cancer or PSA (prostate specific antigen) value >10 ng/mL;
suspected lack of the participant's compliance;
known severe allergies or hypersensitivity to the study drug (active substance or excipients of the formulation);
nown neurogenic bladder (i.e. Parkinson's disease);
suspected or proven urinary infections;
presence of bladder stone.