Clinical trial NCT05525572
Conditions: Erectile Dysfunction With Diabetes Mellitus
Sponsor: University of Miami
Start date: 2024-02-12; Completion date: 2024-08-02
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research study is to evaluate whether the combination of Shockwave Therapy (SWT) with Platelet Rich Plasma (PRP) is synergistic and can reverse the pathology of microvascular Erectile Dysfunction (ED) and enhance erectile function in diabetics patients.

Detailed description:

Arms: arm 1: Participants will receive a combination of 5 weekly extracorporeal shockwave therapy sessions (SWT) and two sessions of autologous platelet-rich plasma (PRP) penile injection.
Interventions: intervention 1: Shockwave Therapy (SWT) intervention 2: Autologous Platelet-Rich Plasma (PRP)
Intervention descriptions: intervention 1: Shockwave Therapy (SWT):

720 shocks will be administered administered in every session to each treated region (left and right corpora cavernosa and crura). Each session will last approximately 20 minutes. A total of 3600 shocks will be administered over 5 weekly sessions. intervention 2: Autologous Platelet Rich Plasma (PRP):

5 mL PRP will be administered via intra-cavernous penile injection with a 30 ± 7 day treatment interval.

Protocol documents:
Prot_SAP_000.pdf: 
The University of Miami, Miller School of Medicine
Desai Sethi Urology Institute
Clinical Research Protocol 
Title:
COMBINING SHOCKWAVE THERAPY AND PLATELET 
RICH PLASMA FOR TREATING ERECTILE DYSFUNCTION 
IN DIABETIC MEN (COCKTAIL-DM)
Protocol No:
UM IRB#: 20220540
NCT#: NCT05525572
Protocol Version:
Version 1.3
Version Date:  5/26/2023
PI/Sponsor:
Telephone:
Fax:
Email:
Thomas A Masterson III, MD
(305) 243 – 6260 (24 hour)
(305) 243 – 3381
TMasterson@med.miami.edu
CONFIDENTIALITY STATEMENT
This document is confidential and proprietary to the University of Miami, Miller School of Medicine, Desai 
Sethi Urology Institute and its affiliates. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be reproduced, published, or otherwise 
disseminated or disclosed without prior written approval of University of Miami Miller School of Medicine 
or its affiliates, except that this document may be disclosed in any medium to appropriate clinical 
investigators, Institutional Review Boards, and others directly involved in the clinical investigation that is 
the subject of this information under the condition that they keep the information strictly confidential
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Investigator Signature Page
Title:
COMBINING SHOCKWAVE THERAPY AND PLATELET RICH PLASMA 
FOR TREATING ERECTILE DYSFUNCTION IN DIABETIC MEN 
(COCKTAIL-DM)
I have read the enclosed protocol. I will ensure the safety of the study subjects enrolled under 
my supervision, and will provide the sponsor with complete, accurate, and timely information on 
this study, as outlined in this Protocol. The signature below constitutes approval of this protocol 
and the attachments and provides the required assurances that this trial will be conducted 
according to all stipulations of the protocol, including local legal and regulatory requirements, 
applicable US federal regulations and (ICF E6) guidelines. I shall hold strictly confidential all 
information pertaining to the study, and that this confidentiality requirement applies to all study 
staff at the site(s) and/or under my supervision. 
    Thomas A Masterson III, MD    
    5/26/23   
    
       Principal Investigator 
Date
_____________________________
Principal Investigator Signature
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Table of Contents
List of Abbreviations and Definition of Terms................................................................................................................5
Protocol Synopsis ...............................................................................................................................................................6
Protocol Title ........................................................................................................................................................................8
1.
Background ...................................................................................................................................................................................8
1.1
Platelet-based therapies.........................................................................................................................................................8
1.2
Platelet-rich plasma treatment for erectile dysfunction....................................................................................................9
1.3
Energy-based treatments for erectile dysfunction...........................................................................................................10
1.4
Combination Restorative Therapy for Erectile Dysfunction...........................................................................................10
2.
Study Objectives.......................................................................................................................................................11
2.1
Primary Objective:.................................................................................................................................................................11
2.2
Secondary Objective:............................................................................................................................................................11
3.
Study Endpoints .......................................................................................................................................................11
3.1
Primary Endpoints ................................................................................................................................................................11
3.2
Secondary Endpoints (efficacy):.........................................................................................................................................11
3.3
Exploratory Endpoints: ........................................................................................................................................................11
4.
Study Location..........................................................................................................................................................11
4.1
Additional Study Sites ..........................................................................................................................................................12
5.
Study Population ......................................................................................................................................................12
5.1
Inclusion criteria:...................................................................................................................................................................12
5.2
Exclusion criteria: .................................................................................................................................................................12
6.
Identification and Enrollment of Subjects ............................................................................................................13
6.1
Recruitment and Pre-screening ..........................................................................................................................................13
6.2
Payment to Subjects.............................................................................................................................................................13
6.3
Informed Consent..................................................................................................................................................................13
6.4
Withdrawal Criteria................................................................................................................................................................14
7.
Procedures Involved ................................................................................................................................................14
7.1
Schedule of Events: ..............................................................................................................................................................14
7.2
Description of Study Procedures........................................................................................................................................16
7.3
Description of Study Visits ..................................................................................................................................................17
8.
Investigational Product............................................................................................................................................18
8.1
Preparation of PRP................................................................................................................................................................18
8.2
Administration of Investigational Therapies.....................................................................................................................18
9.
Data Management.....................................................................................................................................................19
9.1
Case Report Forms (CRFs)..................................................................................................................................................19
9.2
Source Documents................................................................................................................................................................19
9.3
Study Monitoring, Auditing, and Inspecting .....................................................................................................................19
10.
Data and Specimen Banking ..............................................................................................................................20
10.1
Storage of Data ......................................................................................................................................................................20
10.2
Specimen Banking ................................................................................................................................................................20
11.
Safety Monitoring and Reporting ......................................................................................................................20
11.1
Adverse Events (AEs)...........................................................................................................................................................20
11.2
Serious Adverse Events (SAEs)..........................................................................................................................................21
11.3
Treatment Emergent Serious Adverse Events (TE-SAEs) ..............................................................................................21
12.7
Confidentiality and Objectivity............................................................................................................................................25
13.
Statistical Considerations ..................................................................................................................................25
13.1
Data Analysis Plan ................................................................................................................................................................25
14.
Risks and Benefits...............................................................................................................................................25
14.1
Risks to Subjects...................................................................................................................................................................25
14.2
Potential Benefits to Subjects.............................................................................................................................................25
15.
Privacy & Confidentiality ....................................................................................................................................25
15.1
Data collection .......................................................................................................................................................................26
15.2
Data Storage...........................................................................................................................................................................26
15.3
Biospecimens ........................................................................................................................................................................26
16.
Ethical Considerations........................................................................................................................................26
16.1
Regulatory Authority Approval ...........................................................................................................................................26
16.2
Ethics Approval .....................................................................................................................................................................27
16.3
Conflict of Interest.................................................................................................................................................................27
17.
Publications ..........................................................................................................................................................27
18.
References ............................................................................................................................................................28
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List of Abbreviations and Definition of Terms
AE
Adverse Events
BPH
Benign Prostatic Hyperplasia
BRB
Biomedical Research Building
CNS
Central Nervous System
CRF
Case Report Form
CTCAE
Common Terminology Criteria for Adverse Events
eCRF
Electronic Case Report Form
ED
Erectile Dysfunction
EDITS
Erectile Dysfunction Inventory of Treatment Satisfaction
EDV
End Diastolic Velocity
GCP
Good Clinical Practice 
HIPAA 
Health Information Portability and Accountability Act
ICF
Informed Consent Form
ICH
International Conference of Harmonization
ICI
Intracavernosal Injection
IEC
Institutional Ethics Committee
IIEF
International Index of Erectile Function
IIEF-EF
Erectile Function Subdomain Score
IRB
Institutional Review Board
ISCI
Interdisciplinary Stem Cell Institute
MCID
Minimal Clinically Important Difference
mL
Milliliter
ng/dL
Nanograms Per Deciliter
PDE5i
Phosphodiesterase 5 inhibitor
PPP
Platelet Poor Plasma
PRFM
Platelet Rich Fibrin Matrix
PRP
Platelet Rich Plasma
PSV
Peak Systolic Velocity
RCT
Randomized Controlled Trial
SAE
Serious Adverse Events
SEP3
Sexual Encounter Profile
SOP
Standard Operating Procedure
SWT
Low-intensity Shockwave Therapy
TE-SAE
Treatment Emergent Serious Adverse Events
UM
University of Miami
VAS
Visual Analogue Pain Scale
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Protocol Synopsis
TITLE
COMBINING SHOCKWAVE THERAPY AND PLATELET RICH PLASMA FOR 
TREATING ERECTILE DYSFUNCTION IN DIABETIC MEN (COCKTAIL-DM)
SPONSOR
University of Miami, Miller School of Medicine - Department of Urology
PHASE OF STUDY
Phase I/II
STUDY THERAPY
Autologous Platelet-Rich Plasma (PRP) + Low-intensity Shockwave Therapy (SWT)
STUDY DESIGN
Single arm, Open Label, Pilot Trial
ROUTE OF 
ADMINISTRATION 
Intracavernosal Injection (PRP) + extracorporeal shockwave therapy (SWT) 
SUBJECT 
POPULATION
15 male subjects between the age of 30-80 with Mild or Mild-to-Moderate ED and 
controlled Diabetes Mellitus (DM)
STUDY 
OBJECTIVES 
Primary: To investigate biochemical markers of neo-angiogenesis in patients before 
and after PRP injection + SWT 
Secondary: To study efficacy and incidence of adverse events and safety of PRP 
injection + SWT treatment in men with mild-moderate ED, as measured by IIEF.
INVESTIGATION 
PLAN
15 men with Erectile Dysfunction (ED) of organic origin and Diabetes (Type 1 or Type 2), 
that meet all of the inclusion and none of the exclusion criteria, will be enrolled and will 
receive PRP+SWT.
Autologous PRP injection +  SWT therapy. All subjects in this group will receive 2 sessions 
of autologous PRP penile injection with 30 ± 7 day treatment interval. 5mL of PRP will be 
injected at each session. Additionally, patients will receive a total of 3600 shocks over a 
five-week period, starting at initial PRP injection.
DURATION OF 
STUDY
7 months (1 month screening, 5 weeks of therapy sessions, 6 months of follow-up).
DEFINITION OF 
ENDPOINTS
Primary:
-
Changes in markers of vasodilation (eNOS, nNOS), neo-angiogenesis (VEGF, CD-31), 
and systemic markers of endothelial function (EPCs, SDF-1α, and SCF). 
Secondary:
-
Differences in Doppler ultrasound parameters (PSV and EDV) from baseline to 6 
months post-therapy.
-
Treatment satisfaction as assessed by EDITS questionnaire in all subjects.
-
Incidence of Serious Adverse Events experienced up to 6 months post-therapy. 
Exploratory:
-
Change in IIEF-EF score from baseline to 3 and 6 months post-therapy.
-
Percentage of subjects that achieve minimal clinically important difference (MCID) in 
IIEF-EF from baseline to 3 and 6 months post-therapy. 
Percentage of subjects who either decrease or discontinue use of PDE5i after three 
months post-therapy
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Protocol Synopsis
INCLUSION 
CRITERIA
1. Be Male
2. Be 30 to 80 years of age (inclusive).
3. Be able to provide written informed consent.
4. Have a diagnosis of mild to moderate ED (12-21) or mild ED (22-25) 
based on IIEF-EF questionnaire score.
5. Have diagnosis of Diabetes Mellitus (Type 1 or Type 2), as documented 
by history of Hemoglobin A1C > 7% OR on medical therapy for Diabetes.
6. Be in a stable relationship and have a minimum of 2 sexual attempts per 
month for at least one month prior to enrollment. 
7. Agree to comply with all study related tests/procedures.
EXCLUSION 
CRITERIA
1. Previous penile surgery of any kind (except circumcision and condyloma 
removal), such as penile lengthening, penile cancer surgery, penile 
plication, grafting.
2. Previous history of priapism, penile fracture, Peyronie’s Disease, or 
penile curvature that negatively influences sexual activity,
3. Abnormal morning serum testosterone level defined as a value lower 
than 300 ng/dL (±5%).
4. Psychogenic ED as determined by study investigator.
5. Patients using ICI for management of ED
6. Patients with generalized polyneuropathy, neurological conditions, or 
psychiatric disease (such as bipolar disorder or depression).
7. Have a serious comorbid illness or condition that, in the opinion of the 
investigator, may compromise the safety or compliance of the subject or 
preclude successful completion of the study.
8. History of consistent treatment failure with PDE5 inhibitors for therapy of 
ED.
9. Poorly controlled diabetes as indicated by Hemoglobin a1c > 7.5%.
10.Use of antiplatelet medication
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Protocol Title
COMBINING SHOCKWAVE THERAPY AND PLATELET RICH PLASMA FOR 
TREATING ERECTILE DYSFUNCTION IN DIABETIC MEN (COCKTAIL-DM)
1. Background
1.1 Platelet-based therapies
Platelet-derived therapies are a growing trend across multiple medical and surgical 
specialties including dermatology, ophthalmology, cardiology, colorectal surgery, plastic 
surgery and mainly orthopedics [1-2]. One of the most well described platelet-based 
therapies is autologous platelet-rich plasma (PRP) [3]. PRP is derived from the 
centrifugation of whole blood with a separator gel to remove the red and white blood cells. 
The resulting supernatant has a greater than four-fold increase in platelets and other 
plasma proteins [1]. This concentrate is then administered via injection. PRP has been 
frequently used for orthopedic conditions such as bone and soft tissue trauma, 
inflammatory conditions, and chronic pain syndromes [3-4]. Evidence suggests that 
platelets play an important role not only in coagulation but also in regulation of body 
metabolism, promotion of the wound healing, tissue regeneration, vascular remodeling 
and inflammatory/immune responses through secretion of growth factors, cytokines and 
chemokines [4-5]. These biologically active proteins include transforming growth factor-
β, platelet-derived growth factor, platelet-derived epithelial growth factor, insulin- like 
growth factor, vascular endothelial growth factor, basic fibroblast growth factor, as well as 
many others [6]. When platelets are activated, they release these growth differentiation 
factors, facilitating even nerve repair and regeneration [7-8]. Growth factors act locally 
and are implicated in many aspects of natural wound healing, including chemotaxis, cell 
proliferation, cell differentiation and angiogenesis. They also control and conduct 
synthesis, modification and degeneration of extracellular matrix proteins. Coordination of 
these cellular and molecular processes is integral to proper wound healing and tissue 
regeneration [9]. The key role of platelets in these processes makes them an attractive 
candidate for therapies aimed at accelerating natural healing, as well as tissue 
regeneration.
Autologous blood-based biomaterials are promising therapeutic options for varied 
pathology. Rapid generation of therapeutic material following collection allows for point-
of- care therapy [10]. Furthermore, anautologous therapy avoids the need for 
immunosuppression and eliminates concerns of rejection. Newer strategies to prolong 
the anti-inflammatory and wound healing properties of platelets have focused on creating 
a fibrin matrix (platelet rich fibrin matrix, PRFM) to bind the platelets and prevent 
extravasation from the site of injection, thereby addressing the concern of early washout 
with PRP [11]. In addition, PRFM offers a potential scaffold for tissue ingrowth and may 
allow continued release of platelet-related factors for a longer duration. Across multiple 
disciplines, PRP has been used both as a primary treatment modality and as a 
supplement to other therapies in hopes of supplementing wound healing, tissue 
regeneration, and angiogenesis. Although most of the studies focusing on PRP injections 
have been relatively small and heterogenous, they largely support the concept of 
administration in terms of safety, while efficacy remains uncertain. Finally, the concept of 
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autologous therapy has be shown in the real world that it is particularly attractive to 
patients [10].
1.2 Platelet-rich plasma treatment for erectile dysfunction
Erectile dysfunction (ED) affects as many as 1 in 4 men, and evidence indicates that 
incidence is rising [12-13]. The pathophysiology is multifactorial, but the most common 
pathophysiology, vasculogenic erectile dysfunction, has as first sign endothelial 
dysfunction secondary to inflammation [14]. The most common treatments for ED aim to 
improve endothelial function through augmentation of the nitric oxide pathway [15]. 
Return of potency after surgical injury of CNS partially depends on axon regeneration in 
the remaining neural tissue [16]. The process of regeneration and functional recovery of 
peripheral nerve is slow and is influenced by many factors [17] such as extracellular 
matrix, neurotrophic factors, and cellular components [18]. Recent advances in the 
understanding of molecular pathways and their physiological role demonstrate that 
growth factors are an important part of the development, maintenance, and regeneration 
of the nervous system [19]. Various growth factor neuromodulatory strategies, including 
insulin-like growth factor (IGF-I) and neurotrophic factors, are investigated to identify 
agents that may have neuroprotective and regenerative function after the occurrence of 
peripheral nerve injury. Accumulating evidence indicates that neuroimmunophilin ligand 
(such as FK506) plays a significant role in neural regeneration and upregulation of 
neuronal nitric oxide synthase (nNOS), as well as in the recovery of erectile function after 
CN injury occurrence [20-21]. FK506 neuroprotection after CN injury is mediated by 
antioxidative/nitrosative and anti- apoptotic pathway [22]. When platelets are activated, 
they release many kinds of growth differentiation factors and a few types have been found 
to facilitate nerve repair and regeneration. Moreover, corporeal dysfunction due to smooth 
muscle atrophy or other inracavernosal pathology can lead to corporo-venous occlusive 
erectile dysfunction despite a normal arterial inflow. Rejuvenating the Corporeal tissues 
with PRP, which is well known for its growth and healing factors, is a possible modality 
as a potential treatment for erectile dysfunction according to Alkhayal et al [23]. In their 
retrospective study examining the efficacy of one intra-cavernosal PRP injection to 40 ED 
patients, they reported that mean IIEF-5 score before treatment was 13 (5-20) and post 
treatment IIEF-5 = 17 (7-24), (p < 0.001). Other studies have shown similar results with 
minimal side effects, no serious adverse reactions and potential efficacy (Table 1) [23-
26].
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Table 1: Summary of published studies and abstracts
To date, there are no treatments that address the underlying cause of endothelial 
dysfunction, although LIST treatment for ED has shown promising results. Platelet-
derived therapies targeting inflammation and promoting tissue/nerve regeneration and 
may represent a potential treatment option towards this direction. Despite growing 
evidence to the efficacy of PRP, no randomized placebo-controlled studies exist. 
1.3 Energy-based treatments for erectile dysfunction
Shockwave therapy has been utilized by urologists for other ailments, such as treatment 
of kidney stones through a non-invasive manner. Interest in the use of low-intensity 
shockwave therapy for erectile dysfunction was augmented with success seen in 
preclinical models. The hypothesis for SWT’s mechanistic actions is neo-angiogenesis, 
recruitment of progenitor cells and resident stem cells, improvement of microcirculation, 
vasodilation with subsequent increase in nitric oxide, decrease in fibrosis, and nerve 
regeneration. There have been 13 published clinical studies regarding use of SWT for 
ED. Multiple systematic reviews and meta-analyses have been performed for SWT for 
ED, and there is consensus that SWT shows promise in the treatment for ED. 
1.4 Combination Restorative Therapy for Erectile Dysfunction
The development of ED therapeutics that focus on neurovascular regeneration and repair 
strategies are of great importance. A large body of pre-clinical work has demonstrated 
the effect of SWT alone (monotherapy) on angiogenesis and progenitor / stem cell 
recruitment for ED [2, 3, 8-11]. PRP monotherapy importantly is also supported by well-
defined mechanistic insights obtained from rigorously conducted animal studies [12-19]. 
All the previous studies in humans have evaluated either IIEF scores and / or penile 
Doppler ultrasound hemodynamic parameters, but there has not been evaluation of the 
treatment as a combination. The proposed mechanisms of both interventions would 
Author
Year
Number 
of 
Patients
Patient 
Population
Administration
Followup
Adverse Events
Conclusion
Banno 
[26]
2017
N=9
Penile 
Rehab 
PRP ICI into Pnies 
with Vacuum 
Device
4 weeks
No  AEs reported
PRP may represent a safe and viable option as 
a supplementary therapy for penile 
rehabilitation. Particularly notable is the 
prospect of zero side effects.
Matz [24]
2018
N=16
Erectile 
dysfunction, 
Peyronies 
Disease
PRP with CaCl ICI 15.5m
Minor: Bruising 1, 
Mild Pain 4.              
Major: none
PRFM injections for ED, PD, and female SUI are 
feasible and safe. Although the limited data is 
suggestive of efficacy, a placebo control will 
be required in subsequent efforts for 
confirmation
Epifanova 
[25]
2019
N=10
Erectile 
Dysfunction
6 injections PRP 
with CaCl2 ans 
Shockwave
60 Days
No AEs reported
There were no serious adverse events as well 
as severe adverse events. Erectile dysfunction 
symptoms in all men participated in the study 
significantly decreased after treatment with 
PRP-therapy and extracorporeal shockwave 
therapy 
Alkhayal 
[23]
2018
N=40
Erectile 
Dysfunction
1 injection PRP
> 1 month
No AEs reported
Platelet rich plasma is a safe and efficacious 
option for penile rejuvination and 
improvement of erectle dysfunction
Human Studies of PRP for ED
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suggest that the combination therapy would act in a synergistic manner, with superiority 
over monotherapy. Success of our proposed work could fundamentally change the 
standard of care for ED and substantially improve the quality of life for tens of millions of 
men.
2. Study Objectives
2.1 Primary Objective:
To investigate of the underlying mechanisms of PRP and SWT in men with mild-moderate 
ED and Diabetes.
Exploratory:
-
Change in IIEF-EF score from baseline to 3 and 6 months post-therapy.
-
Percentage of subjects that achieve minimal clinically important difference (MCID) in 
IIEF-EF from baseline to 3 and 6 months post-therapy. 
-
Percentage of subjects who either decrease or discontinue use of PDE5i after three 
months post-therapy
2.2 Secondary Objective:
To study the treatment safety and efficacy of PRP and SWT treatment in men with mild-
moderate ED and Diabetes.
3. Study Endpoints
3.1 Primary Endpoints 
-
Changes in markers of vasodilation (eNOS, nNOS), neo-angiogenesis (VEGF, CD-
31), and systemic markers of endothelial function (EPCs, SDF-1α, and SCF).
3.2 Secondary Endpoints (efficacy):
-
Differences in Doppler ultrasound parameters (PSV and EDV) from baseline to 6 
months post-therapy.
-
Treatment satisfaction as assessed by EDITS questionnaire in all subjects.
-
Incidence of Serious Adverse Events experienced up to 6 months post-therapy.
3.3 Exploratory Endpoints:
-
Change in IIEF-EF score from baseline to 3 and 6 months post-therapy.
-
Percentage of subjects that achieve minimal clinically important difference (MCID) in 
IIEF-EF from baseline to 3 and 6 months post-therapy. 
-
Percentage of subjects who either decrease or discontinue use of PDE5i after three 
months post-therapy
4. Study Location
The study will be funded by the CTSI pilot award (GR019191) and coordinated by the 
University of Miami (UM), Miller School of Medicine, Desai Sethi Urology Institute. All 
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study visits will take place in the Department of Urology clinics, (PAC: 1150 NW 14th 
Street, Suite 309, University of Miami Miller School of medicine, Miami, FL. & Lennar: 
5555 Ponce De Leon, 3rd floor, Coral Gables, FL.) PRP preparation and SWT therapy 
administration will take place in the PAC andrology lab and clinic.
4.1 Additional Study Sites
No additional study sites.
5. Study Population
15 males with ED of organic origin and diabetes. All patients will be regular PDE5i 
users/responders. Men with ED will be evaluated by IIEF-EF domain and eligible patients 
will be enrolled in this open label pilot study. Participants who do not meet eligibility criteria 
will be considered a screen failure and will not receive the study therapy.
5.1 Inclusion criteria:
In order to participate in this study, a patient must:
1) Be Male.
2) Be 30 to 80 years of age (inclusive).
3) Be able to provide written informed consent.
4) Have a diagnosis of mild to moderate ED (12-21) or mild ED (22-25) based on 
IIEF-EF questionnaire score.
5) Have diagnosis of Diabetes Mellitus (Type 1 or Type 2) as documented by 
history of hemoglobin A1C > 7% OR on medical therapy for Diabetes.
6) Be in a stable relationship and have a minimum of 2 sexual attempts per month 
for at least one month prior to enrollment.
7) Agree to comply with all study related tests/procedures.
5.2 Exclusion criteria:
In order to participate in this study, a patient must not have any of the following:
1) Previous penile surgery of any kind (except circumcision and condyloma 
removal), such as penile lengthening, penile cancer surgery, penile plication, 
grafting.
2) Previous history of priapism, penile fracture, Peyronie’s Disease, or penile 
curvature that negatively influences sexual activity.
3) Abnormal morning serum testosterone level defined as a value lower than 300 
ng/dL (±5%).
4) Psychogenic ED as determined by study investigator.
5) Patients using ICI for management of ED
6) Patients with generalized polyneuropathy, neurological conditions, or psychiatric 
disease (such as bipolar disorder or depression).
7) Have a serious comorbid illness or condition that, in the opinion of the investigator, 
may compromise the safety or compliance of the subject or preclude successful 
completion of the study.
8) History of consistent treatment failure with PDE5 inhibitors for therapy of ED.
9) Poorly controlled diabetes as indicated by Hemoglobin a1c > 7.5%.
10) Use of antiplatelet medication.
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6. Identification and Enrollment of Subjects
6.1   Recruitment and Pre-screening
The research coordination team may develop materials to aide in recruitment. This may 
include, but is not limited to, informational videos and brochures which provide education 
about erectile dysfunction and include information about the study; physician referral letter 
templates which can be used to promote awareness of the study in the urology 
community; flyers/posters which can be utilized at approved clinic locations and as part 
of health fair materials; templates for print advertisements which can be utilized in 
newsprint and media campaigns. Not all materials have been developed prior to trial 
initiation, however each of these recruitment methods will be reviewed and approved by 
the IRB prior to use.
Pre-screening of subjects includes reviewing medical records and imaging studies for 
inclusion/exclusions prior to consent. From the review of subjects’ medical records and 
imaging studies on file, subjects who are determined to have a diagnosis of erectile 
dysfunction of organic origin and have mild-moderate erectile function as assessed by 
IIEF-EF, as stated in Section 5.1, and also do not have evidence in their medical record 
of study exclusions stated in Section 5.2, are eligible to be consented to the study.
Investigators will inform research staff of potential participants who have been identified 
through pre-screening so the subjects can be approached to discuss the study and 
conduct the informed consent session. No study procedures will take place prior to the 
subjects signing of the informed consent form. 
6.1.1 Waiver of Authorization for Use and Disclosure of Protected Health 
Information (HIPAA) 
A partial waiver of HIPAA is requested for recruitment purposes only. All Protected Health 
Information (PHI) collected by the study investigator and/or study personnel from patient 
records JHS and/or UHealth will be destroyed at the earliest opportunity. All Protected 
Health Inform (PHI) that is acquired from JHS and/or UHealth will not be re-used or 
disclosed to any other person or entity, except as required by law or for authorized 
oversight of the research study or for other research for which the use or disclosure of 
PHI is permissible.
6.2   Payment to Subjects
No payments will be made to subjects as compensation for their participation in this study. 
The subjects will not be asked to pay for the treatments or participation in study either. 
6.3   Informed Consent
6.3.1 Consenting Process
All subjects must provide written consent to participate in this study. An informed consent 
form (ICF) will be given to each subject. The ICF will contain all United States federally 
required elements, all International Conference of Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) required 
elements, and Health Insurance Portability and Accountability Act Authorization (HIPAA) 
information in language that is understandable to the subject. The informed consent 
includes descriptions of all study related procedures, all possible risks to participant, and 
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the time commitment involved with participating. All consent forms will have IRB approval. 
The ICF must be understandable to the subject. Translation of ICFs will be done in 
accordance with local IRB procedures.
Potential participants will be approached by one of the study investigators or research 
coordinators. Information regarding study participation will be provided to the potential 
participant prior to consent. Subjects will be given ample time to review the ICF and ask 
questions before signing. The Investigator or designee and the subject must both sign 
and date the ICF after review, and before the any study procedures are performed. The 
subject will receive a copy of the signed and dated form, and the original will be retained 
in the site study files. The research staff member obtaining consent will document the 
informed process in the subject’s chart for monitoring purposes. The Investigator or 
his/her designee must emphasize to the subject that study participation is entirely 
voluntary and that consent regarding study participation may be withdrawn at any time 
without penalty or loss of benefits to which the subject is otherwise entitled.  
6.3.2 Non-English-Speaking Subjects
In addition to English-speaking subjects, Spanish-speakers will also be included in the 
trial. A certified translated version of the IRB approved English consent form will be made 
available to non-English speakers. Spanish version questionnaires and other patient-
facing materials will also be made available.
6.4 Withdrawal Criteria
All subjects who either screen fails, is withdrawn from the study, or has completed all 
visits should be de-enrolled from the research database within 2 business days, in 
accordance with university policies (or respective institutional policy).
Subjects may be withdrawn from the study for any of the following reasons:
a) A subject does not meet the eligibility criteria (the subject will be considered a 
screen failure).
b) A subject withdraws consent.
c) A subject expires during protocol participation from causes other than the study 
treatment (not due to adverse events).
d) At the discretion of the principal investigator for issues of non-compliance, or other 
behavioral factors.
7. Procedures Involved 
15 men with Erectile Dysfunction (ED) of organic origin, that meet all of the inclusion and 
none of the exclusion criteria, will be enrolled to receive PRP+SWT in an open-label 
fashion. 
Autologous PRP injection + SWT therapy. All subjects in this group will receive 2 sessions 
of autologous PRP penile injection with 28 ± 2 day treatment interval. 5mL of PRP will be 
injected at each session. Additionally, patients will receive a total of 3600 shocks over a 
five-week period, starting at initial PRP injection.
7.1 Schedule of Events: 
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The events table for the conduct of this study is shown below:
Table1:
Schedule of Events
Screening
Treatment
Follow Up
Time Point
Week 0
Week 1
Week 2
Week 3
Week 4
Month 3
Month 6
 Event
0-30 days 
before 
randomization
Day 0
Day 7 ± 
2
Day 14 
± 2
Day 21 
± 2
Day 28 
± 2
Day 90 ± 
14
Day 180 ± 
14
Informed Consent
X
 
 
 
 
 
 
 
Demographics
X
 
 
 
 
 
 
 
Medical History
X
 
 
 
 
 
 
 
Physical Exam
X
 
 
 
 
 
 
 
Doppler Ultrasound
X
 
 
 
 
 
 
X
IIEF
X
 
 
 
 
 
X
X
EDITS
 
 
 
 
 
 
X
X
Questionnaires
VAS
 
X
X
X
X
X
 
 
Laboratory Tests*
X
 
 
 
 
 
 
 
EPC-CFUs
X
 
 
 
 
 
X
X
Brachial FMD
X
 
 
 
 
 
X
X
PRP Injection
 
X
 
 
 
X
 
 
Shockwave Therapy
 
X
X
X
X
X
 
 
Concomitant 
Medications/Therapy
X
X
X
X
X
X
X
X
Review Adverse 
Events
 
X
X
X
X
X
X
X
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7.2 Description of Study Procedures 
7.2.1 Informed Consent: Refer to Section 6.3 for details regarding the informed consent 
process. Study procedures will be completed only after participants have signed 
the informed consent documentation.
7.2.2 Demographics: Demographic characteristics will be recorded including: date of 
birth, gender, marital status, race and ethnicity.
7.2.3 Medical History: Assessment of current and past medical, surgical, and social 
history will be conducted.
7.2.4 Physical Examination: Genitourinary/Reproductive system physical exam will be 
performed.
7.2.5 Doppler Ultrasound:  Penile Doppler ultrasound will be performed as standard of 
care for the management of erectile dysfunction. Results from within the past 12 
months can be extracted from the medical record for use in this study.
7.2.6 International Index of Erectile Function (IIEF) Questionnaire: This validated 
15-item self-evaluation scale provides pre and post treatment clinic evaluations of 
erectile function, orgasmic function, sexual desire, satisfaction in sexual 
intercourse and general satisfaction. If the subject has completed the IIEF 
questionnaire within the past 6 months, those results may be requested and used 
for the purpose of this research study. Questionnaires will be completed prior to 
therapy at injection visits.
7.2.7 Erectile 
Dysfunction 
Inventory 
of 
Treatment 
Satisfaction 
(EDITS) 
Questionnaire: This is a psychometrically sound questionnaire used to assess 
satisfaction with medical treatment modalities for erectile dysfunction.
7.2.8 Visual Analogue Pain Scale (VAS): The visual analog scale (VAS) is a validated, 
subjective measure for acute and chronic pain. Scores are recorded by making a 
handwritten mark on a line that represents a continuum between “no pain” and 
“worst pain”.
7.2.9 Laboratory Testing: Hematology, chemistry, hemoglobin A1C, and serum 
testosterone lab test results will be collected at screening. If any standard of care 
labs testing has been performed within 12 months of the date of the screening visit, 
those results may be used for the purpose of this study.
7.2.10 Endothelial Progenitor Cell Colony Forming Units (EPC-CFUs): Peripheral 
blood samples will be collected from participants for isolation of EPCs using Ficoll-
Paque density gradient. Plasma will be aliquoted and stored for future analysis. 
Five million cells will be seeded on 6-well Fibronectin-coated dishes (BD 
Biosciences) in CFU-Hill medium (Stem Cell Technologies, cat#05900)4 and 
incubated at 37oC in humidified 5% CO2. Non-adherent cells will be collected after 
48 hours, and 1 million cells will be seeded on 24-well Fibronectin-coated dishes. 
On day 5, EPC-CFUs will be counted in 6 wells and the average will be obtained.
7.2.11 Brachial Artery Flow Mediated Dilation (FMD): FMD% is a non-clinical measure; 
it is a tool used specifically for research to obtain an understanding the functionality 
of the vascular endothelium. 2D ultrasound will be used to measure Flow Mediated 
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Diameter percent change (FMD%). All measurements of the brachial artery 
diameter and FMD% will be performed in the morning, in a quiet and dark room 
and at controlled ambient temperature. Subjects will fast overnight and refrain from 
consuming caffeine, nicotine, or other stimulants for at least 8 hours prior to 
ultrasound and should refrain from vigorous exercise for at least 4 hours prior to 
ultrasound. Subjects are permitted to drink water and take medications (except 
PDE5 inhibitors) as usual. The subject will rest for 10 minutes in the supine position 
prior to scan. The subject's right arm will be comfortably immobilized in an 
extending position, allowing for ultrasound scanning of the brachial artery 5–10 cm 
above the antecubital fossa. In each examination, recording of vessel images will 
be followed by inflation of a cuff to supra-systolic pressure (40 to 50 mmHg above 
systolic pressure) for 5 minutes. Then the cuff will be deflated, and the brachial 
artery diameter will be imaged and recorded for 3 minutes.
7.2.12 Platelet-Rich Plasma (PRP) Injection: Approximately 120mL of blood will be 
collected from participants for preparation of investigational product. Refer to 
Section 8 for description of Investigational Product (IP) preparation and 
administration.
7.2.13 Shockwave Therapy (SWT): In the treatment group, patients randomized will 
receive 5 weekly sessions, in which 720 shocks of treatment energy will be applied 
in every session to each treated region (left and right corpora cavernosa and crura) 
for a total of 3,600 shocks. Refer to Section 8 for description of Investigational 
Product (IP) preparation and administration.
7.2.14 Concomitant Medications: Review of current use of prescription and over the 
counter (OTC) medications. Participants must discontinue use of PDE5i 
medications throughout the duration of the study.
7.2.15 Review Adverse Events: Refer to Section 11 for description and reporting of 
adverse and serious adverse events
7.3 Description of Study Visits
7.3.1 Screening Visit
Visit 1 (0 – 28 days before therapy): The basic work-up will take place, including medical 
and sexual history, as well as necessary lab tests (testosterone, prolactin, hematology, 
chemistry), if not available during the last 12 months prior to screening. Subjects will 
complete the IIEF questionnaire. We will ensure that patients have 4 attempts for 
intercourse Screening visit can occur on same day as first injection + SWT. Refer to table 
1 for procedures to be performed at the Screening visit.
7.3.2 Treatment Visits: Week 0 – Week 4
Upon evaluation of eligibility, subjects will be randomized to one of the two parallel study 
groups using an online program, and initiate treatment on the same day. 
There will be 5 treatment visits for all groups, each occurring at weekly intervals (± 2 
days), for a total duration of five weeks.  Subjects will complete a Visual Analogue Scale 
(VAS) pain score after the end of each treatment. Refer to table 1 for all procedures to be 
performed at the treatment visits.
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7.3.3 Follow Up Visits: Months 3 and 6 Post-Treatment
Follow up visits will occur within 90 ± 14 days (Month 3) and 180 ± 14 days (Month 6) 
days after final treatment visit. Refer to table 1 for procedures to be performed at the 
follow up visits visit.
8. Investigational Product
8.1 Preparation of PRP
Autologous Platelet-Rich Plasma (PRP) is prepared by taking 120 mL aliquots of 
anticoagulated peripheral blood (120 mL whole blood and 16 mL anticoagulant citrate 
dextrose formula A) obtained from each subject by venipuncture. Each aliquot is 
processed by an autologous platelet separator (Arthrex Angel, Arthrex Inc., Naples, 
Florida) to yield 3-10 mL of PRP from each subject. Platelet poor plasma (PPP) can be 
added to PRP to achieve the desired injection volume. This system is FDA approved by 
510(k) for “clinical laboratory or intraoperatively at the point of care for the safe and rapid 
preparation of platelet poor plasma and platelet concentrate (platelet rich plasma) from a 
small sample of whole blood or a small mixture of blood and bone marrow”. For 
participants randomized to the control arm, blood will still be drawn but will not be 
processed to make PRP.
8.2 Administration of Investigational Therapies
8.2.1 Platelet-Rich Plasma
The patient will be positioned supine. A sterile 
field will be developed with Betadine prep of the 
genitalia, sterile gloves and a sterile extremity 
drape. A total of 20 mL of 1% lidocaine will be 
drawn up using an 18-gauge needle and will be 
subcutaneously administered using a 27-gauge 
needle into the subcutaneous tissue at the base 
of the penis to obtain a dorsal nerve block. A 1/4-
inch Penrose drain will be used as a tourniquet 
by placing it at the base of the penis and 
maintaining it in place under tension by a sterile 
clamp. A maximum of 5 mL of PRP will be 
infused steadily over a two-minute period – 
approximately 2.5 mL each into the right and left 
corpus cavernosum, as shown in Figure 1. The injections will be performed at this slow 
speed (each side over 2 minutes of infusion) to minimize injury to the platelet cells. In the 
control arm, men will be administered injectable normal saline that will be injected in a 
similar manner as the PRP. 
Following administration of PRP or normal saline, compression of the penis will be 
achieved with a clenched fist for 20 minutes. At 20 minutes, the tourniquet will be 
removed, and a compressive dressing will be placed around the penile shaft. The patient 
will be instructed to remove the compression bandage in 4 hours and to contact the study 
coordinators if he experiences any problems. 
8.2.2 Low Intensity Shockwave Therapy
Figure 1: Diagram of PRP Injection
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Figure 2 shows the MoreNova device, which is a 
Linear Shockwave (LISW) transducer capable of 
delivering shockwaves to a treatment region 
confined to a narrow rectangle. Shockwaves 
generation follows the electromagnetic principle. 
Linear Shockwaves (LISW) has been under 
evaluation, as a treatment for ED for the last five 
years. The present study will utilize a device called 
“MoreNova”, in which shockwaves are focused 
onto line segments for improved organ coverage. 
Shockwaves produced by "MoreNova" are aimed 
at the left and right corpora cavernosa and the 
crura. The study is aimed at determining the safety 
and efficacy of this new type of LISW in the treatment of ED. The treatment session lasts 
approximately 20 minutes and may be performed in an office environment. Treatment is 
applied in the physician’s office.
All subjects will receive 5 weekly sessions, in which 720 shocks of treatment energy will 
be applied in every session to each treated region (left and right corpora cavernosa and 
crura). 
9. Data Management
Data will be entered from source documents into eCRFs which are maintained in an online 
research database. The investigator will ensure data integrity by confirming the CRF’s 
are attributable, legible, contemporaneous, original, accurate, and complete.
9.1 Case Report Forms (CRFs)
The Investigator or designee must record all required subject data, and an explanation 
must be documented for any missing data. This study will use electronic case report forms 
(eCRF) for data entry and database storage.
9.2 Source Documents
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. 
Source data are contained in source documents.  Examples of these original documents, 
and data records include: hospital records, clinical and office charts, laboratory notes, 
memoranda, subjects’ diaries or evaluation checklists, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and 
complete, and records kept at medical technical departments involved in the clinical trial. 
All corrections to study data will be made by drawing a single line through the information 
to be corrected without obscuring it. All corrections will be initialed, dated and explained, 
if necessary, in accordance with good clinical practice (GCP) guidelines.
9.3 Study Monitoring, Auditing, and Inspecting
The investigator will permit study-related monitoring, audits, and inspections by the IRB, 
government regulatory bodies, and University compliance and quality assurance groups 
of all study related documents. The investigator will ensure the capability for inspections 
of applicable study-related facilities.
Figure 2: MoreNova SWT Device
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10.Data and Specimen Banking
10.1
Storage of Data
Data will be maintained on research team hardware, and subject charts will be stored in 
a filing room maintained by Department of Urology. Clinical follow up and laboratory data 
will be stored in a locked room, with access only to authorized personnel. It is up to the 
principal investigator’s discretion as to how long non-FDA study essential documents are 
retained.
10.2
Specimen Banking
Bio-specimens will be reserved for future testing and stored at -80 degrees Celsius in 
equipment maintained by ISCI in the Biomedical Research Building (BRB) (address: 1501 
NW 10th avenue Miami FL 33136). Each specimen must have a corresponding requisition 
form to track the chain of custody from time of collection to time of processing and/or 
storage.
11.  Safety Monitoring and Reporting
11.1
Adverse Events (AEs)
An adverse event (AE) is defined as any untoward medical occurrence associated with 
the use of a drug in humans, whether or not considered drug related. An AE can be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the study. The event does not need to have a causal 
relationship with treatment. Common Terminology Criteria for Adverse Events Version 5 
(CTCAE) will be used for describing AEs. All urological and/or reproductive system AEs 
will be recorded. For all other AEs, only events greater than grade 2 will be recorded.
Based on our own pilot data assessing SWT 
and PRP monotherapy, we have compiled the 
following data on adverse events (Table 2):
We anticipate there to be few adverse events 
related to the study. Based on the four published 
studies and abstracts, including 75 men, only 
minor adverse events were reported (Bruising 1, 
Mild Pain 4). No serious adverse events were 
observed [23-26].
11.1.1 Expectedness
An adverse event is considered “unexpected” if it is not listed in the investigator brochure, 
protocol, ICF, or is not listed at the specificity or severity that has been observed; or, if an 
investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application.
Anticipated adverse events for this study include: Pain, Bruising, Swelling, Edema, 
Allergy, Penile Fracture, and/or New Penile Curvature.
11.1.2 Severity
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Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5.0) will be used 
to assess severity of adverse events. All grade 3-5 adverse events, regardless of 
association with the investigational therapy, will be entered into study database and 
reviewed at research committee meetings.
11.2
Serious Adverse Events (SAEs)
A serious adverse event (SAE) is defined as an AE which, in the view of the Investigator 
results in: 1) Death; 2) a life-threatening event (i.e. an event in which the subject was at 
risk of death at the time of the event; it does not refer to an event which hypothetically 
might have caused death if it were more severe); 3) inpatient hospitalization of > 24 hours 
or prolongation of existing hospitalization; 4) a significant disability/incapacity; or 5) a 
congenital anomaly/birth defect. Other important medical events may be considered 
SAEs if, in the opinion of the Investigator, they jeopardize the subject or require 
intervention to prevent one of the other outcomes listed above. Based on prior 
investigations, we do not anticipate any SAEs related to the study procedures [23-26].
11.3
Treatment Emergent Serious Adverse Events (TE-SAEs) 
A treatment emergent serious adverse event (TE-SAE) is defined as any serious adverse 
event for which there is a reasonable possibility that the investigational product caused 
the adverse event. For the purposes of safety reporting, “a reasonable possibility” means 
there is evidence to suggest a causal relationship between the study product/procedures 
and the adverse event.
12. Statistical Considerations
12.1
Data Analysis Plan
Analysis plan: Continuous data will be analyzed using ANOVA with repeated measures, 
or student’s T-Test (where applicable) in order to compare differences between the 
treatment and control groups. For categorical data, Fisher’s Exact test to determine 
differences between groups. Statistical significance will be evaluated using α=0.05. 
13.  Risks and Benefits
13.1
Risks to Subjects
We anticipate there to be few adverse events related to the study. Based on the four 
published studies and abstracts, including 75 men, only minor adverse events were 
reported (Bruising 1, Mild Pain 4). No serious adverse events were observed [23-26]. 
After literature review, we believe this product to be of non-significant risk to patients 
(NSR) and for investigational use in a clinical study protocol. 
Based on published studies, we will record anticipated adverse events to patients include: 
local injection site reaction, penile pain, penile hematoma (bleeding into the tissue), penile 
swelling, allergic reaction to the anesthetic, local infection, penile fracture, or new penile 
curvature. In addition, there may be uncommon or previously unknown risks that might 
occur. We will record every adverse event at every visit systematically.
13.2
Potential Benefits to Subjects
The potential benefits for men randomized to the treatment arm will include improvement 
in erectile function and sexual performance.
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14.  Privacy & Confidentiality
Each subject’s protected health information will remain strictly confidential and shall be 
excluded from the database. Patients deemed eligible to participate in the study following 
evaluation of inclusion/exclusion criteria will be assigned a unique study participant 
identifier number (ex.: COC-DM-01). The first two characters indicate the enrolling site, 
next 5 characters describe the study and phase, and final 3 characters are the unique 
identification number assigned to subjects in sequential order.
The Investigator will retain a cross-referencing record of each subject’s name and 
assigned identifier number. All study data and results will be stored in the electronic 
database. Each study subject will give explicit consent for representatives of the IRB/IEC 
and regulatory authorities to inspect and verify each subject’s medical records and 
collected information. In turn, each study subject will be assured that all their personal 
information will be maintained in the strictest of confidence, and in compliance with 
HIPAA, and all other federal and local laws regulating privacy and data protection. 
Data will be collected from the EMR or subjects at UHealth or JHS. Research subjects 
will sign a HIPAA Authorization before collection of data for this research study. 
14.1
Data collection
Data will include Protected Health information or Personally Identifiable Information.
14.2
Data Storage
Information will be stored on a University of Miami electronic device (e.g. encrypted, 
password-protected computer), and on a cloud-based storage system that is approved 
by the University of Miami. Research data will be entered into the REDCap secure 
electronic database.
The Principal investigator (and/or Study Team members) will record (e.g. write down, 
abstract) the data collected in a manner that does not include any direct identifiers of any 
subject. Instead, the Principal Investigator and/or Study Team members will assign a 
code (that is not derived in whole or in part from any direct or indirect identifiers of the 
individual) to each study subject and link the code to the study subject’s identity. The link 
to each subject’s identity and/ or other identifiable information will be maintained on a 
document separate from the research data. 
14.3
Biospecimens
Biospecimens obtained for this research will be stored in a de-identified, coded manner 
without any direct or indirect identifiers. Biospecimens obtained for this research will be 
stored. When required to transport data or biospecimens for this research, the research 
team will transport the data and biospecimens in a de-identified (or anonymous)manner 
with a link to the individual subject’s identity maintained separately from the data and/or 
biospecimen.
15. Ethical Considerations
15.1
   Regulatory Authority Approval
This study will be conducted in accordance with Good Clinical Practice (GCP) 
requirements described in the current revision of International Conference on 
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Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH) 
Guidelines and all applicable regulations, including current United States Code of Federal 
Regulations (CFR), Title 21, Parts 50, 54, 56, and Title 45, Part 164. Compliance with 
these regulations and guidelines also constitutes compliance with the ethical principles 
described in the current revision of the Declaration of Helsinki.  This study will also be 
carried out in accordance with local legal requirements. 
According to FDA guidance issued to institutional review boards and investigators, we will 
use PRP for ED (an indication not approved on the labeling) while simultaneously 
“bearing the responsibility to be well informed about the product,  base its use on firm 
scientific rationale and on sound medical evidence, and to maintain records of the 
product’s use and effects.”
We believe that according to FDA regulation, the clinical investigation of PRP and SWT 
for ED does not require submission of an IND / IDE since all six of the following conditions 
are met:
i.
it is not intended to be reported to FDA in support of a new indication for use or to 
support any other significant change in the labeling for the drug;
ii.
it is not intended to support a significant change in the advertising for the product;
iii.
it does not involve a route of administration or dosage level, use in a subject 
population, or other factor that significantly increases the risks (or decreases the 
acceptability of the risks) associated with the use of the drug product;
iv.
it is conducted in compliance with the requirements for IRB review and informed 
consent [21 CFR parts 56 and 50, respectively];
v.
it is conducted in compliance with the requirements concerning the promotion and 
sale of drugs [21 CFR 312.7]; and
vi.
it does not intend to invoke 21 CFR 50.24.
15.2
   Ethics Approval
The investigators agree to conduct the study in compliance with the protocol, current good 
clinical practices, and all applicable (local, FDA) regulatory guidelines and standard of 
ethics.
It is the Investigator’s responsibility to ensure that, prior to initiating this study, this protocol 
is reviewed and approved by the appropriate local and/or external IRB.  The composition 
and conduct of this committee must conform to the United States CFR. The IRB/IEC must 
also review and approve the site’s informed consent form (ICF), other written information 
provided to the subject.
If it is necessary to amend the protocol or the ICF during the study, the Sponsor-
Investigator will be responsible for ensuring that the IRB/IEC reviews and approves these 
amended documents. An IRB/IEC approval of the amended protocol and/or ICF must be 
obtained in writing before implementation of the amended procedures and before new 
subjects are consented to participate in the study using the amended version of the ICF.
15.3
  Conflict of Interest
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Any investigator who has a conflict of interest with the study must have the conflict 
reviewed by a properly constituted Conflict of Interest Committee with the Committee-
sanctioned conflict management plan that has been reviewed and approved by the study 
sponsor prior to participation in this study. All investigators will follow the University of 
Miami’s (or applicable institution’s) conflict of interest policy.
16.  Publications
The preparation and submission of manuscripts for publication that contain results from 
this study shall comply with all applicable privacy laws and in accordance with processes 
determined by the University of Miami, Miller School of Medicine.
17.  References
1.
Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol 
2013;9:721-30.
2.
Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. 
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25. Epifanova, M.; Gvasalia, B.; Artemenko, S.; Durashov, M. First results of platelet-rich plasma and low intensity 
extracorporeal shockwave combined therapy for erectile dysfunction. Abstract (Poster) SMSNA 2019, Nashville TN.
26. Banno, J.J.; Kinnick, T.R.; Roy, L.; Perito, P.; Antonini, G.; The efficacy of platelet-rich plasma (prp) as a 
supplemental therapy for the treatment of erectile dysfunction (ed): initial outcomes. Abstract (Poster) SMSNA 2017, 
San Antonio TX.
-       Study #: 20220540        Effective Date: 6/27/2023