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

• ClinicalTrials.gov Identifier: NCT02252367
• Recruitment Status: Completed
• First Posted: September 30, 2014
• Last Update Posted: April 28, 2021
• Sponsor: University of Florence
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Mario Maggi, University of Florence

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 (Clinical Trial)
• 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: December 2015
• Actual Primary Completion Date: January 2019
• Actual Study Completion Date: June 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 Name: 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 :

1. Improvement of LUTS/BPH symptoms [ Time Frame: 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 :

1. Improvement of pressure flow study (PFS) parameters [ Time Frame: 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.
2. Volumetric change of the prostate [ Time Frame: 12 weeks ]
   Prostate volume as assessed by transrectal ultrasound
3. Change in prostate inhomogeneity and in the number of prostatic macrocalcifications [ Time Frame: 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.
4. Variation in genic expression of prostatic inflammation markers [ Time Frame: 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.
5. Variation in serum inflammation markers CRP (C-reactive protein) and ESR (Erythrocyte Sedimentation Rate) [ Time Frame: 12 weeks ]
   CRP measured on serum and ESR measured on blood drawn at baseline and after 12 weeks
6. Improvement in metabolic profile [ Time Frame: 12 weeks ]
   Metabolic parameters will be evaluated (glycaemia, insulinemia, total cholesterol, HDL, triglycerides, HbA1c, mean arterial pressure, waist circumference, body mass index)
7. Variation in seminal plasma IL-8 (interleukin-8) levels [ Time Frame: 12 weeks ]
   Seminal IL-8, a chemokine involved in male genital tract infection/inflammation, will be evaluated.
8. Improvement in erectile function [ Time Frame: 12 weeks ]
   Erectile function will be assessed by using the International Index of Erectile Function-5 (IIEF-5) score.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Italy

Clinica Urologica - Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Sponsors and Collaborators

University of Florence

Eli Lilly and Company

Investigators

• Principal Investigator: Mario Maggi; University of Florence

More Information

Publications:

Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, Roehrborn CG, Serni S, Mirone V, Carini M, Maggi M. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012 May;61(5):994-1003. doi: 10.1016/j.eururo.2012.02.033. Epub 2012 Feb 25.

Gacci M, Vittori G, Tosi N, Siena G, Rossetti MA, Lapini A, Vignozzi L, Serni S, Maggi M, Carini M. A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med. 2012 Jun;9(6):1624-33. doi: 10.1111/j.1743-6109.2012.02718.x. Epub 2012 Apr 17.

• Responsible Party: Mario Maggi, Full Professor of Endocrinology, University of Florence
• ClinicalTrials.gov Identifier: NCT02252367
• Other Study ID Numbers: ANDRO-AOUC-2014-01
• First Posted: September 30, 2014
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

Keywords provided by Mario Maggi, University of Florence:

Phosphodiesterase 5 Inhibitors; BPH/LUTS

Additional relevant MeSH terms:

Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms; Pathologic Processes; Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Tadalafil; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents