Clinical Trial With Random Assignment to Evaluate the Efficacy and Safety of Radial Waves for the Treatment of Erectile Dysfunction
Phase: NA
Conditions: Erectile Dysfunction
Sponsor: Boston Medical Group

STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 
TITTLE OF THE STUDY: 
 
RANDOMIZED CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF 
RADIAL WAVES FOR THE TREATMENT OF ERECTILE DYSFUNCTION 
 
NTC 03596047 
 
 
RESEARCHERS: 
 
JOSÉ PABLO SAFFÓN 
CAROLINA SANDOVAL  
JUAN MANUEL MARTINEZ 
HÉCTOR CORREDOR 
ANDRÉS FELIPE GALLEGO 
OLGA URIBE 
 
 
 
Date of the document: June 1, 2017 
 
 
 
 
 

Abstract 
 
Background: Radial waves are an effective therapy for the management of various problems at the 
muscular and joint level, thanks to the effect it has on the activation of microcirculation. The effect 
of these waves on patients with erectile dysfunction is currently unknown; however, it is considered 
possible to help recovery in patients with vascular origin dysfunction by increasing microcirculation 
blood flow in this area. 
 
Objective: To evaluate the efficacy and safety of radial shock waves for the treatment of erectile 
dysfunction. 
 
Patients and methods: Randomized, double-blind clinical trial. The study will include patients of 
legal age with diagnosis of ED and score on the IIEF-EF scale between 11 and 21 points, who 
voluntarily decide to participate and sign the informed consent. Patients with bladder cancer, 
prostate cancer or active colon, ED of psychological origin, any psychiatric disorder, spinal cord 
injury, clinical suspicion of hypogonadism (AMS greater than 36), infections or active lesions of the 
penis or pubic area, ED secondary to treatment with medications (antiandrogenic therapy, use of 
corticosteroids, anti-Parkinson’s, antipsychotics), radical prostatectomy or other radical pelvic 
surgery, history of pelvic radiotherapy, penile implantation, or endocrine diseases that occur with 
ED (acromegaly, gigantism, Addison's disease, hyperprolactinemia, androgenic deficiency), sickle 
cell anemia, and anticoagulated patients will be excluded.  
Patients will be randomly assigned to one of the following treatment arms:  
● Arm 1 (Standard treatment (oral sildenafil) + Radial wave therapy): Sildenafil according to 
the degree of patient involvement + 6 sessions of radial waves. A weekly session of radial 
waves will be applied with the following parameters: 6000 pulses at 1.5-2.6 bar (depending 
on patient tolerance), with a frequency of 17Hz, the frequency should increase to 22HZ the 
first 500 impulses to create mild anesthesia in the area; in all radial wave sessions, 4000 
impulses will be distributed in the body of the penis in scanning technique and 2000 
impulses in the perineal area.  
 
● Arm 2 (Standard treatment (oral sildenafil) + Placebo therapy): Sildenafil according to the 
patient's degree of affectation + 6 sessions of placebo therapy. There will be a weekly 
session of placebo wave therapy, using the respective device to prevent the patient from 
receiving the radial wave. The same parameters of the "real" therapy will be used: 6000 
pulses at 2.6 bar, with a frequency of 17 Hz; in all radial wave sessions, 4000 impulses will 
be distributed in the body of the penis in scanning technique and 2000 impulses in the 
perineal area. 
 
Measurements will be made of the EHS and IIEF-EF scale scores, of the use of medication and of the 
possible adverse events of the therapy, at the beginning and end of the treatment, and one month 
after the therapies are finished. 
 

Expected impact: Knowing the effectiveness and safety of radial waves for the treatment of erectile 
dysfunction will allow having a scientific basis for new treatment alternatives for men with this 
disease. 
 

Introduction 
Erectile dysfunction (ED) is defined as the persistent inability to reach and / or maintain an erection 
sufficient to allow a satisfactory sexual relationship (1). Epidemiological information on ED shows 
that it is a condition that has a high prevalence and incidence worldwide and that mainly affects 
men over 40 years of age (2). The prevalence of ED in the general population of men under 40 years 
of age is approximately between 1% and 10% (3). Both prevalence and severity increase with age, 
in men between 60 and 69 years of age, the prevalence of erectile dysfunction increases from 20% 
to 40%, and this range can increase from 50% to 100% in men between 70 and 80 years old (3-6).  
Currently, there are different pharmacological and non-pharmacological treatments for erectile 
dysfunction, among which are the administration of medicines for oral use, intracavernous and 
intraurethral, lifestyle modification, vacuum devices, psychotherapy, extracorporeal therapy with 
low intensity shock waves (Li-ESWT), vascular surgery for selected cases, and alternative therapies 
(7-14).  
In addition to these treatments, the therapy with radial waves seems to be effective for the 
management of this pathology, since it increases microcirculation blood flow (15). Studies without 
a control group suggest improvement in the IIEF-5 scale of erectile dysfunction in patients who 
received this type of wave therapy, however there are no controlled studies to evaluate the 
effectiveness and safety of this therapy (16, 17)1. 
Boston Medical Group (BMG) is a global alliance of medical centers that share research information 
and treatment methods for male sexual dysfunction. This alliance has locations around the world 
that include Latin America, Europe, and the United States. In Colombia, Boston Medical Group aims 
to perform primary research in erectile dysfunction with the purpose of determining scientific 
evidence that allows the dissemination of research results that lead to a better understanding of 
ED, its diagnosis, treatment and prognosis. This will impact on the clinical management and finally 
on the health outcomes of patients with this condition. 
The objective of this study is to determine the efficacy and safety of radial wave therapy for the 
treatment of patients with moderate to mild to moderate erectile dysfunction seen at BMG 
branches in Colombia and Peru. 
 
 
 
                                                          
1 Pokorny P, Turcan P, Prochazka M, Prochazkova J. (2015). Evaluation of radial extracorporeal shock wave 
therapy in the treatment of erectile dysfunction. Journal of Sexual Medicine. 12. 233-233. / 
Perelman J, Hepnar VD (2017) Men's Power-Pressure Wave Erectile Regeneration-Therapy: an Early 
Assessment. Urol Nephrol Open Access J 4 (4): 00136. DOI: 10.15406 / oneaj.2017.04.00136 

Theoretical framework 
Erectile dysfunction is the persistent inability to achieve and maintain an erection sufficient to allow 
a satisfactory sexual relationship (1). It is a benign problem related to the organic and psychological 
aspects of health that has a significant impact on the quality of life of the affected people and their 
families. 
Research conducted in the United States reported a prevalence of ED between 44% and 52% in men 
between 40 and 70 years of age, 17.2% of which had minimal ED, 25.2% had moderate ED and 9.6% 
had complete ED (5). In Latin America the study "Erectile Dysfunction in North South America” 
(DENSA) reported that more than half of the respondents had some degree of ED (53.4%) with a 
higher prevalence of the minimum over the moderate or severe, the minimum ED had its peak in 
the population between 60 and 69 years, while moderate and severe was seen more in subjects 
between 70 and 79 years (18). 
Among the risk factors associated with erectile dysfunction are cardiovascular disease, obesity, 
smoking, hypercholesterolemia, metabolic syndrome, major pelvic surgeries (radical prostatectomy 
of any kind), pelvic radiotherapy, prior priapism and trauma of cavernous or pelvic bodies (3,5,6). 
ED is a disease that occurs in many cases as comorbidity of other diseases in different proportions, 
for example, in 52% of hypertensive patients, in 64% of diabetics and in 90% of patients with 
depression (4, 11). 
ED can be primary if it occurs from puberty and is usually associated with congenital vascular 
anomalies, or secondary, late onset after having a period of normal erectile function, associated 
with the aforementioned pathologies.  
According to the etiology it can be predominantly psychogenic or predominantly organic, in which 
case it must be clarified whether its origin is vascular, endocrinological, neurological, induced by 
drugs, other causes or of mixed etiology. 
There are several treatments for the management of erectile dysfunction. Among the most used are 
the so-called 5 phosphodiesterase inhibitors (PDE5 Inhibitors), however, they have not proven to 
have a healing effect on erectile dysfunction (19) and it is for this reason that options that can act 
on the physiological mechanisms that generate erectile dysfunction should be sought.  
 
Radial wave therapy 
Radial waves are pressure waves used for the treatment of different diseases of the musculoskeletal 
system. Among the differences with shock waves are the duration of the pulse, which is much 
longer. 
Radial waves are generated by collision of solid bodies. The compressed air accelerates a projectile 
(bullet) that hits an impact body and part of the produced kinetic energy is transmitted to this body 
generating a translational movement in a short distance at a low speed until the coupled tissue or 
the hand piece decelerates its movement (15, 20). 
The movement of the impact body is transferred to the patient's tissue at the point of contact, from 
where it propagates in the form of a radial pressure wave, which in the skin or superficial tissue is 
strong and decreases as it advances to deeper tissues (15, 20). 

The effect of radial waves is less intense than focal shock waves, causes the disintegration of fibrosis 
and calcifications, and increases blood microcirculation and metabolic activity in the treated site 
(15, 20). There is evidence that radial wave therapy has a poor penetration to tissue (3cm), a low 
impact and limited biological effects (20, 21), however, this therapy has demonstrated effectiveness 
in the management of pain, muscle and tendon inflammation (15).  
 
Although the effect of this type of waves is not known in erectile dysfunction, the effect on 
microcirculation increase suggests that it may be useful as a complementary therapy to the 
treatments currently used. In addition to this there is low-quality evidence that suggests a possible 
beneficial effect of radial waves. 
 
     
   
 
 
 
 

Justification 
Erectile dysfunction is a pathology with a moderate prevalence which increases and worsens as the 
population ages. It affects not only the sexual and reproductive health of the sufferer and his 
partner, but also his mental health, often producing disorders depressives that diminish the quality 
of life of people and their families.  
Pharmacological treatment is not effective in 100% of patients and does not lead to changes in the 
physiology-pathology of erectile dysfunction (14), but acts as an adjuvant in the symptomatology, 
therefore, the management of erectile dysfunction should focus on the treatment of the 
pathophysiological causes that generate it and therefore other treatment options that can act in 
this way should be sought.  
Therapy with (Li-ESWT) for erectile dysfunction has been proposed as a new alternative in the 
management of erectile dysfunction (12, 22-25). Its mechanisms of action can be multiple, but are 
summarized in the increase in vascular flow to the corpora cavernosa generated by a process of 
neovascularization (26) secondary to angiogenesis promoted by endothelial growth factors such as 
vascular endothelial growth factor (VEGF), endothelial cell growth factors and cell proliferation 
nuclear antigen (27), in addition to the increase in the concentration of vasodilator substances such 
as nitric oxide. The therapy with Li-ESWT has been presented as a therapeutic option, which does 
not replace the other alternatives, but which adds efficacy to traditional ED management (28). 
Likewise, therapy with radial waves arises as a new option for the management of this disease, 
which has been conducted by different specialists given the benefit shown in the increase of blood 
flow and muscle recovery for different musculoskeletal conditions. However, currently there are no 
controlled studies that report on the efficacy and safety of this therapy for the treatment of erectile 
dysfunction (16, 17). For this reason, it is pertinent to carry out a clinical trial that allows obtaining 
valid results and thus making reliable clinical decisions.  
 
 
 
 

Objectives 
 
Primary 
To evaluate the effectiveness of radial shock wave therapy in patients with moderate erectile 
dysfunction 2 measured as the increase in the average IIFE-EF score at the end of the treatment. 
Secondary 
1. To evaluate the effectiveness of radial shock wave therapy at one month of follow-up, with 
respect to the change in the average IIFE-EF score. 
2. To evaluate the efficacy of radial shock wave therapy with respect to the average score of 
the erection hardness scale (EHS), at the end of the treatment and at one month of follow-
up, in the intervention and control groups. 
3. To evaluate the effectiveness of radial shockwave therapy, regarding the change in the use 
of sildenafil at the end of treatment and at one month of follow-up, in the intervention and 
control groups. 
4. To compare the incidence of adverse events in the intervention and control groups. 
 
 
 
 
                                                          
2 For this study moderate erectile dysfunction is considered a score on the IIEF-EF scale from 11 to 21, which 
includes the mild to moderate and moderate categories. 

Materials and methods 
 
Type of study 
Randomized, double-blind clinical trial.  
Research hypothesis 
Ho: The change in the score of the IIEF-EF scale in patients with moderate erectile dysfunction3, 
treated with radial wave therapy, is equal to those who receive placebo therapy. 
Ha: The change in the score of the IIEF-EF scale increases at least five points in patients with 
moderate erectile dysfunction treated with radial wave therapy, compared with the score of 
patients receiving placebo therapy.  
Study population 
Patients diagnosed with erectile dysfunction of vascular origin who are treated at the Boston 
Medical Group facilities in Bogotá.  
Inclusion criteria 
1. Men older than 18 years 
2. Erectile dysfunction presents for more than 3 months in more than 50% of intercourse. 
3. IIEF-EF score between 11 and 21. 
4. Patient who agrees to enter the study through the signing of an informed consent. 
 
Exclusion criteria 
1. EHS score of 4 
2. Bladder, prostate or colon cancer. 
3. Patients with ED of psychological origin. 
4. Patients with spinal cord injury. 
5. Patients with anticoagulant use. 
6. Patients with sickle cell anemia. 
7. Patients with clinical suspicion of hypogonadism (AMS greater than 36, Annex 1). 
8. Patients with infections or active lesions of the penis or pubic area. 
9. Patients with ED secondary to drug treatment (antiandrogenic therapy, antidepressants, 
use of corticosteroids, antiparkinsonians, antipsychotics). 
10. Radical prostatectomy or other radical pelvic surgery. 
11. Antecedents of pelvic radiotherapy. 
12. Patients with penile implant. 
13. Endocrine diseases that occur with ED: acromegaly, gigantism, Addison's disease, 
hyperprolactinemia, androgenic deficiency. 
14. Patients with neurological diseases (Parkinson's, CVD, dementia of any origin)  
 
                                                          
3 For this study moderate erectile dysfunction is considered a score on the IIEF-EF scale from 11 to 21, which 
includes the mild to moderate and moderate categories.   

Sample size  
Assuming that the placebo plus drug group has an average change in the score of the IFE-EF scale of 
5 points and that the new wave therapy must have an additional change of at least 5 points to be 
considered clinically relevant, for a power of 80% and a one-tailed level of significance of 97.5%, 
with a standard deviation of 8 points, a sample size of 33 patients was estimated for each group. 
Adjusting for a percentage of losses of 20%, the size per group is 40 patients, for a total of 80 patients 
in the study. These calculations were performed in Stata 15.1®.  
Interventions 
Each patient will be assigned randomly to one of the following groups:  
● Arm 1 (Radial wave therapy + oral treatment): 6 radial waves’ sessions. A weekly session 
of radial waves will be applied with the following parameters: 6000 pulses at 1.5-2.6 bar 
(depending on patient tolerance), with a frequency of 17Hz, the frequency should increase 
to 22HZ the first 500 impulses to create mild anesthesia in the area; in all the sessions of 
radial waves, 4000 impulses will be distributed in the body of the penis in scanning 
technique and 2000 impulses in the perineal area, specifically in the ischiocavernosus and 
bilateral bulbo-sponge muscles. During the period of therapy application, patients will 
receive oral treatment with sildenafil 4 according to the patient's degree of affectation.   
 
● Arm 2 (Placebo therapy + oral treatment): 6 sessions of placebo therapy. There will be a 
weekly session of placebo wave therapy, using the respective device to prevent the patient 
from receiving the radial wave. The same parameters of the "real" therapy will be used: 
6000 pulses at 2.6 bar, with a frequency of 17 Hz; in all the sessions of radial waves, 4000 
impulses will be distributed in the body of the penis in scanning technique and 2000 
impulses in the perineal area. During the period of therapy application, patients will receive 
oral treatment with sildenafil 5 according to the patient's degree of affectation.  
 
The radial waves will be administered with the Masterpuls MP50 device from Storz medical. 
 Primary Outcome   
The primary outcome of this study is the difference in the average score of the IIEF-EF scale (Annex 
3) in at least 5 points at the end of the treatment. 
 
 
Secondary outcomes 
- 
IIEF-EF score after one month of follow-up. 
- 
Erection Hardness Score (EHS) at the end of treatment and one month follow-up: The EHS is a 
unique Likert scale and the version validated in Spanish (35) will be used, which has the following 
score, 0: The penis does not change in size or hardness; 1: The penis increases in size but does 
                                                          
4 This is the standard treatment. 
5 This is the standard treatment 

not become rigid; 2: The penis is rigid but not enough to penetrate; 3: The penis is rigid enough 
for penetration but not completely hard; and 4: The penis is completely hard or rigid (Annex 4).  
- 
Change in the dose or use of sildenafil. 
- 
Incidence of adverse events. 
 
Safety 
It will be determined by the presence of adverse events. These will be evaluated at the end of each 
of the therapies and a month of follow-up. This variable will be dichotomous as the presence or 
absence of adverse events. Additionally the type of adverse event and the degree of severity will be 
recorded. 
 
Randomization  
The assignment of patients to the treatment arms will be done with the method of randomization 
by balanced blocks of unequal cells. The assignment of the treatment will be centralized, so once 
the patient agrees to participate in the study and signs the informed consent, an email should be 
sent to the research center ( csandoval@bostonmedical.com.co ) who will only inform the therapist 
which is the group (intervention or control) that corresponds to the patient. 
 
To conceal the assignment sealed opaque envelopes will be used, this envelope will be opened once 
the request is generated in each center, after the patient has voluntarily accepted to participate in 
the study and the informed consent process has been carried out with signature of the written 
document.  
 
Neither the patient, the attending physician, nor the professional who applies the questionnaires 
will know the group to which the patient was assigned.  
 
Techniques, procedures, data collection and processing 
The subjects who attend consultation for erectile dysfunction at the Boston Medical Group clinics 
in Bogotá (Colombia) and Lima (Peru), will be treated as usual according to the institutional 
management protocols and screened to determine if they meet the eligibility criteria. If so, they will 
be invited to participate in the research project and the informed consent process will be carried 
out in which the objectives, risks, benefits, procedures and other relevant research data will be 
explained. 
Once the patient has voluntarily accepted to participate in the study and the informed consent 
document has been signed, an email will be generated to the research center to request the group 
to which the patient will be assigned. 
A baseline measurement of the IIEF-EF and the EHS will be made before starting the intervention; 
In addition, the AMS questionnaire should be completed to rule out hypogonadism. Once the 
treatment is completed, patients must complete the IIEF-EF and EHS scales in the last treatment 
session. In this same session, the patient will be evaluated for adverse events; later, they will have 

a medical follow-up one month after the end of the treatment, in which measurements of 
effectiveness and safety of the therapy will be made again. If the patient cannot attend the medical 
follow-up, the surveys will be sent by email on the day of the follow-up appointment and the patient 
will be contacted by telephone (Figure 2).  
Radial wave therapy will be applied with the following parameters: There will be a weekly session 
of 6 sessions of radial waves. A weekly session of radial waves will be applied with the following 
parameters: 6000 pulses at 1.5-2.6 bar (depending on patient tolerance), with a frequency of 17Hz, 
the frequency should increase to 22HZ the first 500 impulses to create mild anesthesia in the area; 
in all the sessions of radial waves, 4000 impulses will be distributed in the body of the penis in 
scanning technique and 2000 impulses in the perineal area. The application at the perineal level 
should be performed with the patient in the supine position in a low lithotomy position, the testicles 
should be slightly raised to apply the wave on the perineal musculature (ischiocavernosus and 
bilateral bulbospongiosus). 
 
The placebo therapy will be done with the same machine and the same parameters as the actual 
therapy, but the adjustment will be made in the handpiece to eliminate the effect of the radial 
waves.  
 
If there is a difference between placebo therapy and radial wave therapy, patients in the placebo 
arm will receive the intervention arm scheme, one month after the initial treatment.  
All clinical data will be recorded in the electronic medical record of Boston Medical Group and in the 
database of the study, in the latter a code will be used for the identification of research subjects, 
thus avoiding the use of the personal patient data.  At the end of the collection of the total sample, 
the missing clinical information will be extracted from the electronic medical record. This 
information will be exported to a flat file for the corresponding statistical analysis.  
The research team will hold meetings every two weeks to monitor the study to validate the data of 
the base. 
Follow-up  
The research subjects will be followed up one month after the end of the treatment. In the event 
that the patient cannot attend the follow-up, the respective scales will be sent to his e-mail so he 
can process them and return them by the same means; if after 3 days no response is received, a 
research assistant will call him and apply the questionnaires by telephone.  
Statistical Analysis 
A descriptive analysis of the individuals’ baseline characteristics linked to each treatment arm will 
be made, estimating measures of central tendency and dispersion in the case of continuous 
variables, and measures of relative and absolute frequency for categorical variables. 
To evaluate the effectiveness of the therapy, the change in the IIEF-EF scale will be compared at the 
end of the treatment with the baseline score for each of the arms, using parametric tests in case the 

data present a normal distribution, or nonparametric tests otherwise. This same analysis will be 
done for the scores at the one-month follow-up. 
For the EHS scale, the change in at least 1 point will be evaluated, in any of the established 
measurements. The association between the change in the score and the received treatment will 
be evaluated estimating the relative risk with its respective confidence interval.  
The percentage of patients that decrease or discontinue the use of sildenafil in each group will be 
estimated, comparing the proportion between the groups at the end of the therapy scheme and the 
month of follow-up, using the Chi-square test. 
The incidence of adverse events for each of the intervention groups will be estimated and the value 
between them will be compared using the Chi-square test.  
In addition to the comparison between groups, stratified analyzes will be performed with 
multivariate regression models to determine how each intervention adjusted for covariates, such as 
comorbidities or additional treatments. 
An interim analysis will be done once 60% of the total number of patients has completed the 
treatment (main outcome).  
Expected impact 
 
The main contribution of this study is for the scientific community and for patients with erectile 
dysfunction, by collecting scientific evidence of quality that allows to make a decision about the use 
of radial waves for the management of erectile dysfunction. 
Ethical aspects 
 
The research will be conducted in compliance with the legal and ethical guidelines described in 
Resolution 8430 of 1993 of the Colombian Ministry of Health and other national regulations; The 
principles for human research enunciated in the Declaration of Helsinki of the World Medical 
Association, and the ethical guidelines contemplated by the Council of International Organizations 
of Medical Sciences -CIOMS and the Belmont Report- will be respected and complied with. 
According to Article 11 of Resolution 8430 of 1993 of the Ministry of Health, it is considered that 
this is an investigation with risk greater than the minimum for the research subjects, which fully 
respects the provisions of article 8 of the same. On the other hand, and in accordance with this 
legislation, approval will be requested from an Ethics Committee that authorizes the development 
of the investigation.  
The intervention to be evaluated has a proven effectiveness in other conditions and the reports 
published in scientific evidence show that the rate of adverse events is very low. The intervention 
will be administered by personnel with all the technical capacity and experience required, both for 
the administration of the intervention and for the management of possible adverse events.  

Each subject will be informed of all possible consequences (regardless of their probability of 
occurrence) of participating in this investigation. An informed consent will be explained and 
completed and the individual will be free to accept participation in the study without causing any 
inconvenience with their treatment (Annex 5). 
Likewise, the confidential management of the information collected in response to the need not to 
violate the privacy of each research subject will be guaranteed. The databases will be kept in the 
Boston Medical Group offices and will only be accessed by the researchers participating in the study.  
It is guaranteed that the researchers possess the technical competence required for this study and 
that they have the necessary tools for the care and use of research data.