Daniele Santi1, Antonio R M Granata2, Alessandro Guidi2, Elisa Pignatti3, Tommaso Trenti2, Laura Roli2, Roberto Bozic2, Stefano Zaza2, Chiara Pacchioni2, Stefania Romano2, Jerzy Roch Nofer2, Vincenzo Rochira3, Cesare Carani2, Manuela Simoni4. 1. Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany santi.daniele@gmail.com. 2. Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany. 3. Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany. 4. Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany.
Abstract
OBJECTIVE:Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men. DESIGN: A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted. METHODS: In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10 mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry). RESULTS:IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects. CONCLUSION: This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism in diabetic, hypogonadal men.
RCT Entities:
OBJECTIVE:Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabeticmen. DESIGN: A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted. METHODS: In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10 mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry). RESULTS: IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects. CONCLUSION: This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism in diabetic, hypogonadal men.
Authors: Giuseppe Defeudis; Rossella Mazzilli; Marta Tenuta; Giovanni Rossini; Virginia Zamponi; Soraya Olana; Antongiulio Faggiano; Paolo Pozzilli; Andrea M Isidori; Daniele Gianfrilli Journal: Diabetes Metab Res Rev Date: 2021-09-21 Impact factor: 8.128
Authors: Andrea M Isidori; Elisa Giannetta; Riccardo Pofi; Mary A Venneri; Daniele Gianfrilli; Federica Campolo; Claudio M Mastroianni; Andrea Lenzi; Gabriella d'Ettorre Journal: Andrology Date: 2020-07-03 Impact factor: 4.456