madman
Super Moderator
ABSTRACT
Introduction: Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential “cure” for ED.
Aim: The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption.
Methods: A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet-rich plasma (PRP), and restorative-related technologies like low-intensity shockwave therapy (LiSWT).
Main Outcome Measures: Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures.
Results: To date, there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, through technologies such as LiSWT that have established relative safety.
Conclusions: Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/ placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice.
INTRODUCTION
Erectile dysfunction (ED) refers to the inability to achieve or maintain an erection sufficient for satisfactory sexual performance and has a significant negative impact on both men and their partners.1 Recent estimates suggest the overall prevalence of ED in North America is between 22 and 58%.2 This number is expected to grow in tandem with the aging population.3 Several studies show ED is strongly associated with older age and increasingly common comorbidities such as hypertension, cardiovascular disease, and diabetes.2,4
Initial treatments include couples therapy and oral pharmacologic agents, namely phosphodiesterase type-5 (PDE5) inhibitors, as well as local pharmacotherapies to the penis like intra-urethral suppositories and intracavernosal injections.5,6 Though these treatments demonstrate good efficacy for men with mild to moderate ED there remains a cohort who either cannot tolerate these medications, have direct contraindications, or represent a hard-to-treat ED population.6 These include men with post-prostatectomy ED, diabetes mellitus, and men with severe ED related to peripheral vascular disease and smoking.7,8 For the medication refractory patients, surgical treatment involves the placement of a penile prosthesis. Penile implants have high patient satisfaction, but this surgery is not without risks and potential complications.6,9 Sexual medicine providers recognize the importance of restoring spontaneous physiologic erections. In fact, most men and their partners report spontaneous erections preferable to pharmacologic and surgical approaches to ED.1,10 Therefore, the field has actively sought novel approaches that reverse organ dysfunction and restore the neurovascular function of the penile vasculature.
Restorative therapies are based on the concept of repairing or replacing diseased tissue by stimulating endogenous regenerative capabilities. These treatments provide a promising alternative to the current management paradigms and represent a transition from modalities that only address disease symptoms to interventions aimed at restoring the structure and function of erectile tissue.11 Restorative therapies include treatments such as stem cell therapy (SCT) or platelet-rich plasma (PRP) and technologies based on regenerative principles, such as low-intensity shock wave therapy (LiSWT)12 which stimulate endogenous stem cell mobilization to diseased tissue. Many of these erectogenic treatments have been studied pre-clinically; however, there are limitations in the translation of these findings to humans (due to both study design and species to species variability) that require clinical trials. To this end, randomized controlled trials with appropriately powered placebo arms are severely lacking, thus limiting the widespread acceptance of these treatments.13 The aim of this position statement is to review the clinical studies that have been conducted utilizing restorative therapies and provide context
*LOW-INTENSITY SHOCK WAVE THERAPY (LISWT)
*STEM CELL THERAPY/ STROMAL VASCULAR FRACTION
*PLATELET-RICH PLASMA (PRP)
SMSNA POSITION STATEMENT ON RESTORATIVE THERAPIES
The SMSNA does not advocate for restorative therapies to be offered or used in routine clinical practice. However, the SMSNA strongly supports the development of novel erectogenic therapies, given that many men with ED either fail currently available treatments or find them unpalatable. Restorative therapies are an exciting avenue for this work, as they utilize regenerative medicine technologies to re-establish organ function. The emergence of restorative therapies such as low-intensity shock wave therapy, stem cell therapies (including SVF), and platelet-rich plasma therapy represents a new frontier of investigative therapies for ED treatment. At the moment, however, the cumulative body of clinical trials for restorative therapies (Table 1) is largely incomplete, and many questions remain unanswered. The society, however, recognizes the need for adequately powered, multicenter, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure that efficacy and safety are demonstrated for any novel ED therapy.69 The society agrees with the regulatory agency pathway of approval including safety and efficacy studies to achieve our goals in diverse patient populations. Without FDA approval, the use of any novel therapy is considered off-label. To date, there is an absence of robust clinical trial data supporting restorative therapies’ efficacy in humans, although relative safety has been established for SCT/ SVF and LiSWT. Furthermore, the precise treatment parameters for LiSWT such as energy settings, dosing, frequency of use, and duration of therapy among others remain to be fully elucidated. Cell sources allowing optimization of these evolving SCT and SVF therapies remain, as yet, undefined. Unlike conventional pharmacologic therapies which generally have a primary, well-defined target, the mechanism of action of restorative therapies is likely to be complex, involving a number of pathways inherent to the regenerative potential of the host. The SMSNA both advocates for and supports the application of high-quality research, both pre-clinical and clinical, aimed at better understanding the mechanisms involved, the magnitude and durability of benefit, and the long-term safety of restorative therapies. Thus, given the current lack of regulatory agency approval for any restorative (regenerative) therapies for the treatment of ED and until such time as approval is granted, SMSNA believes that the use of shock waves or stem cells/SVF are investigational and platelet-rich plasma is experimental and should only be conducted under research protocols in compliance with Institutional Review Board approval at little or no cost to the patient. Specifically, the SMSNA does not feel that it is appropriate or ethical for providers to advertise or otherwise make implicit or explicit claims of efficacy for these therapies pending further data. Similarly, patients considering such therapies should be fully informed as to the lack of data demonstrating clinically relevant efficacy and consent regarding the potential benefits and risks. In summary, at the current time, the SMSNA does not advocative for restorative therapies to be offered or used in routine clinical practice.
Introduction: Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential “cure” for ED.
Aim: The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption.
Methods: A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet-rich plasma (PRP), and restorative-related technologies like low-intensity shockwave therapy (LiSWT).
Main Outcome Measures: Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures.
Results: To date, there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, through technologies such as LiSWT that have established relative safety.
Conclusions: Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/ placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice.
INTRODUCTION
Erectile dysfunction (ED) refers to the inability to achieve or maintain an erection sufficient for satisfactory sexual performance and has a significant negative impact on both men and their partners.1 Recent estimates suggest the overall prevalence of ED in North America is between 22 and 58%.2 This number is expected to grow in tandem with the aging population.3 Several studies show ED is strongly associated with older age and increasingly common comorbidities such as hypertension, cardiovascular disease, and diabetes.2,4
Initial treatments include couples therapy and oral pharmacologic agents, namely phosphodiesterase type-5 (PDE5) inhibitors, as well as local pharmacotherapies to the penis like intra-urethral suppositories and intracavernosal injections.5,6 Though these treatments demonstrate good efficacy for men with mild to moderate ED there remains a cohort who either cannot tolerate these medications, have direct contraindications, or represent a hard-to-treat ED population.6 These include men with post-prostatectomy ED, diabetes mellitus, and men with severe ED related to peripheral vascular disease and smoking.7,8 For the medication refractory patients, surgical treatment involves the placement of a penile prosthesis. Penile implants have high patient satisfaction, but this surgery is not without risks and potential complications.6,9 Sexual medicine providers recognize the importance of restoring spontaneous physiologic erections. In fact, most men and their partners report spontaneous erections preferable to pharmacologic and surgical approaches to ED.1,10 Therefore, the field has actively sought novel approaches that reverse organ dysfunction and restore the neurovascular function of the penile vasculature.
Restorative therapies are based on the concept of repairing or replacing diseased tissue by stimulating endogenous regenerative capabilities. These treatments provide a promising alternative to the current management paradigms and represent a transition from modalities that only address disease symptoms to interventions aimed at restoring the structure and function of erectile tissue.11 Restorative therapies include treatments such as stem cell therapy (SCT) or platelet-rich plasma (PRP) and technologies based on regenerative principles, such as low-intensity shock wave therapy (LiSWT)12 which stimulate endogenous stem cell mobilization to diseased tissue. Many of these erectogenic treatments have been studied pre-clinically; however, there are limitations in the translation of these findings to humans (due to both study design and species to species variability) that require clinical trials. To this end, randomized controlled trials with appropriately powered placebo arms are severely lacking, thus limiting the widespread acceptance of these treatments.13 The aim of this position statement is to review the clinical studies that have been conducted utilizing restorative therapies and provide context
*LOW-INTENSITY SHOCK WAVE THERAPY (LISWT)
*STEM CELL THERAPY/ STROMAL VASCULAR FRACTION
*PLATELET-RICH PLASMA (PRP)
SMSNA POSITION STATEMENT ON RESTORATIVE THERAPIES
The SMSNA does not advocate for restorative therapies to be offered or used in routine clinical practice. However, the SMSNA strongly supports the development of novel erectogenic therapies, given that many men with ED either fail currently available treatments or find them unpalatable. Restorative therapies are an exciting avenue for this work, as they utilize regenerative medicine technologies to re-establish organ function. The emergence of restorative therapies such as low-intensity shock wave therapy, stem cell therapies (including SVF), and platelet-rich plasma therapy represents a new frontier of investigative therapies for ED treatment. At the moment, however, the cumulative body of clinical trials for restorative therapies (Table 1) is largely incomplete, and many questions remain unanswered. The society, however, recognizes the need for adequately powered, multicenter, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure that efficacy and safety are demonstrated for any novel ED therapy.69 The society agrees with the regulatory agency pathway of approval including safety and efficacy studies to achieve our goals in diverse patient populations. Without FDA approval, the use of any novel therapy is considered off-label. To date, there is an absence of robust clinical trial data supporting restorative therapies’ efficacy in humans, although relative safety has been established for SCT/ SVF and LiSWT. Furthermore, the precise treatment parameters for LiSWT such as energy settings, dosing, frequency of use, and duration of therapy among others remain to be fully elucidated. Cell sources allowing optimization of these evolving SCT and SVF therapies remain, as yet, undefined. Unlike conventional pharmacologic therapies which generally have a primary, well-defined target, the mechanism of action of restorative therapies is likely to be complex, involving a number of pathways inherent to the regenerative potential of the host. The SMSNA both advocates for and supports the application of high-quality research, both pre-clinical and clinical, aimed at better understanding the mechanisms involved, the magnitude and durability of benefit, and the long-term safety of restorative therapies. Thus, given the current lack of regulatory agency approval for any restorative (regenerative) therapies for the treatment of ED and until such time as approval is granted, SMSNA believes that the use of shock waves or stem cells/SVF are investigational and platelet-rich plasma is experimental and should only be conducted under research protocols in compliance with Institutional Review Board approval at little or no cost to the patient. Specifically, the SMSNA does not feel that it is appropriate or ethical for providers to advertise or otherwise make implicit or explicit claims of efficacy for these therapies pending further data. Similarly, patients considering such therapies should be fully informed as to the lack of data demonstrating clinically relevant efficacy and consent regarding the potential benefits and risks. In summary, at the current time, the SMSNA does not advocative for restorative therapies to be offered or used in routine clinical practice.
