Safety and Efficacy of Low Intensity Shockwave for the Treatment of Erectile Dysfunction- Comparison of Two Treatment Schedule
Phase: NA
Conditions: Vasculogenic Erectile Dysfunction
Sponsor: University of Miami

	  
  
Safety  and  Efficacy  of  Low  Intensity  Shockwaves  for  the  Treatment  of  Erectile  
Dysfunction  –  Comparison  of  Two  Treatment  Schedules  
_________________________________________________________________________________________________	  
	  
	  
  
  
  
  
  
IRB:  20160335                        NCT03067987  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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Safety  and  Efficacy  of  Low  Intensity  Shockwaves  for  the  Treatment  of  Erectile  
Dysfunction  –  Comparison  of  Two  Treatment  Schedules  
_________________________________________________________________________________________________	  
	  
  
  
PRINCIPAL  INVESTIGATOR  
  
  Ranjith  Ramasamy,  M.D  
                                                                                                                          Assistant  Professor  
                      Department  of  Urology  
                      1400  N.W.  10th  Avenue  
                      Miami,  Florida  33136  
  Phone:  305-­243-­6596  
  Fax:  305-­243-­4562  
  Email:  Ramasamy@miami.edu  
                  
CO-­PRINCIPAL  INVESTIGATOR  
  
Bruce  Kava,  M.D.  
Professor      
Department  of  Urology  
1400  N.W.  10th  Avenue  
Miami,  Florida  33136  
Phone:  305-­243-­6591  
Fax:  305-­243-­6597  
Email:  Bkava@miami.edu  
              
  BIOSTATITISICAN:     
  
  
Raymond  Balise,  PhD    
  
  
  
  
  
  
Research  Assistant  Professor,    
Department  of  Public  Health  Sciences,  Division  of  
Biostatistics  
Clinical  Research  Bldg,  R-­669  
1120  NW  14th  Street,  Room  1061  
Miami,  FL  33136  
Phone:  (305)  243-­9694      
Fax:  (305)  243-­5544      
rrb28@miami.edu  
  
  
  
  
  
  
  
  
  
  
STUDY  COORDINATOR:  
  
  
Emad  Ibrahim,  
305-­243-­9082  
  
  
  
  
  
  
Assistant  Scientist,  Miami  Project  to  Cure  Paralysis  
eibrahim@med.miami.edu  

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SPONSER:  
  
  
  
  
Direx  System  Corp  
  
  
  
  
  
  
  
  
  
  
  
  
  
VERSION  #:     
  
  
  
1  
  
VERSION  DATE  
  
  
  
May  27,  2016  
	  
	  
	  
TABLE	  OF	  CONTENTS	  
	  
1.	   BACKGROUND	  .....................................................................................................................................	  7	  
1.1	  
Study	  Disease	  ..........................................................................................................................................	  7	  
1.2	  
Study	  Interventions	  ..............................................................................................................................	  9	  
1.3	  
Rationale	  ...................................................................................................................................................	  9	  
1.4	  
Preliminary	  Studies	  ...........................................................................................................................	  10	  
2.	   HYPOTHESIS	  .....................................................................................................................................	  10	  
2.1	  
Alternate	  Hypothesis	  (HA):	  .............................................................................................................	  10	  
2.2	  
Null	  Hypothesis	  (HO):	  .......................................................................................................................	  11	  
3.	   OBJECTIVES	  .......................................................................................................................................	  11	  
3.1	  
Primary	  Efficacy	  Objective	  .............................................................................................................	  11	  
3.2	  
Secondary	  Objectives	  .......................................................................................................................	  11	  
4.	   STUDY	  DESIGN	  .................................................................................................................................	  11	  
4.1	  
Accrual	  goal	  ..........................................................................................................................................	  11	  
4.2	  
Duration	  of	  Study	  Participation	  ...................................................................................................	  11	  
5.	   STUDY	  ENTRY	  AND	  ENROLLMENT	  AND	  WITHDRAWAL	  ............................................	  11	  
5.1	  
Study	  Entry	  ...........................................................................................................................................	  11	  
5.2	  
Enrollment	  Procedure	  ......................................................................................................................	  12	  
5.3	  
Cancellation	  Guidelines	  ...................................................................................................................	  12	  
6.	   PATIENT	  SELECTION/ELIGIBILITY	  CRITERIA	  ..................................................................	  13	  
6.1	  
Inclusion	  (Eligibility)	  Criteria	  .......................................................................................................	  13	  
6.2	  
Exclusion	  (Eligibility)	  Criteria	  ......................................................................................................	  13	  
6.3	  
Study	  Population	  ................................................................................................................................	  14	  
7.	   STUDY	  DESIGN,	  CLINICAL,	  RADIOLOGICAL,	  LABORATORY	  AND	  SURGICAL	  
EVALUATIONS	  ..........................................................................................................................................	  14	  
7.1	  
Study	  Design	  .........................................................................................................................................	  14	  
7.2	  
Screening	  Evaluations	  and	  Procedures	  ....................................................................................	  14	  
7.3	  
Pre-­‐‑Treatment	  Procedures	  and	  Evaluations	  ..........................................................................	  15	  
7.4	  
Treatment	  Procedures	  .....................................................................................................................	  15	  

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Follow-­‐‑Up	  Procedures	  and	  Evaluations:	  ..................................................................................	  17	  
8.	   ADVERSE	  EVENTS	  ..........................................................................................................................	  17	  
8.1	  
Expected	  Adverse	  Events	  ................................................................................................................	  17	  
8.2	  
Serious	  Adverse	  Events	  ...................................................................................................................	  17	  
9.	   DATA	  AND	  SAFETY	  MONITORING	  PLAN	  .............................................................................	  18	  
10.	   STATISTICAL	  CONSIDERATIONS	  .............................................................................................	  18	  
10.1	  
Primary	  Study	  Endpoints	  ................................................................................................................	  18	  
10.2	  
Secondary	  Endpoints	  ........................................................................................................................	  18	  
10.3	  
Endpoint	  definitions	  .........................................................................................................................	  19	  
10.4	  
Sample	  size,	  accrual	  and	  study	  duration	  ..................................................................................	  19	  
10.5	  
Statistical	  Analysis	  and	  Power	  calculation	  ..............................................................................	  19	  
10.6	  
Randomization:	  ...................................................................................................................................	  20	  
11.	   INVESTIGATORS	  RESPONSIBLITIES	  ......................................................................................	  20	  
11.1	  
Investigator	  Responsibility/Performance	  ...............................................................................	  20	  
11.2	  
Confidentiality	  .....................................................................................................................................	  21	  
11.3	  
Informed	  Consent	  and	  Permission	  to	  Use	  Protected	  Health	  Information	  .................	  21	  
11.4	  
Source	  Documentation	  and	  Investigator	  Files	  ......................................................................	  22	  
11.5	  
Recording	  and	  Processing	  of	  Data	  ..............................................................................................	  22	  
11.6	  
Non-­‐‑Protocol	  Research	  ....................................................................................................................	  23	  
11.7	  
Ethics	  .......................................................................................................................................................	  23	  
11.8	  
Essential	  Documents	  for	  the	  conduct	  of	  a	  clinical	  trial	  ......................................................	  23	  
12.	   Appendix	  I	  International	  Index	  of	  Erectile	  Function	  (IIEF	  –	  EF)	  Questionnaire.	  923	  
13.	   Appendix	  II	  Sexual	  Encounter	  Profile	  (SEP-­‐‑	  Questions	  2	  and	  3)10	  ............................	  25	  
14.	   Appendix	  III	  Global	  Assessment	  Question	  (GAQ)10	  .........................................................	  25	  
15.	   Appendix	  IV	  EHS-­‐‑	  Erection	  Hardness	  Score.11	  ...................................................................	  26	  
16.	   List	  of	  Abbreviations	  .....................................................................................................................	  26	  
17.	   Study	  Calendar	  .................................................................................................................................	  27	  
18.	   Study	  Design	  Flowchart:	  ..............................................................................................................	  28	  
19.	   References:	  ........................................................................................................................................	  29	  
  
  
  
  
  
  
  
  
  
  
  

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Investigator’s  Statement  
  
  
  
This  clinical  trial  shall  be  conducted  in  compliance  with  the  protocol,  as  referenced  herein,  
and  all  applicable  local,  national,  and  international  regulatory  requirements  to  include,  but  
not  be  limited  to:  
  
•   International   Conference   on   Harmonization   (ICH)   Guidelines   on   Good   Clinical  
Practice  (GCP)  
•   Ethical  principles  that  have  their  origins  in  the  Declaration  of  Helsinki    
•   Food  and  Drug  Administration  (FDA)  Code  of  Federal  Regulation  (CFR):  
o  
Title  21CFR  Part  50  and  45  CFR  Part  46,  Protection  of  Human  Patients  
o  
Title  21CFR  Part  54,  Financial  Disclosure  by  Clinical  Investigators  
o  
Title  21CFR  Part  56,  Institutional  Review  Boards  
o  
Title   45   CFR   Parts   160,   162,   and   164,   Health   Insurance   Portability   and  
Accountability  Act  (HIPAA)  
  
As  the  Principal  Investigator,  I  understand  that  my  signature  on  the  protocol  constitutes  
my   agreement   and   understanding   of   PI   responsibilities   to   conduct   the   clinical   trial   in  
accordance  to  the  protocol  and  applicable  regulations.    Furthermore,  it  constitutes  my  
understanding   and   agreement   that   any   changes   initiated   by   myself,   without   prior  

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agreement  in  writing  from  the  Sponsor,  shall  be  defined  as  a  deviation  from  the  protocol,  
and  shall  be  formally  documented  as  such.  
  
  
I  understand  that  my  signature  constitutes  agreement  and  understanding  of  acceptance  
of   the   defined   responsibilities   of   a   Sponsor-­Investigator   as   defined   by   the   protocol,  
applicable   FDA   Regulations,   and/or   business   contracts,   but   does   not   in   any   capacity  
relieve  me  of  my  responsibilities  as  the  Sponsor-­Investigator.    Additionally,  my  signature  
constitutes  my  understanding  and  agreement  that  any  changes  to  the  protocol  shall  be  
implemented  timely  with  my  review  and  approval  prior  to  implementation.  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
INVESTIGATOR'S	  AGREEMENT	  
	  
	  
I  confirm  that  I  have  read  this  protocol,  I  understand  it,  and  I  will  work  according  to  this  
protocol  and  to  the  ethical  principles  stated  in  the  latest  version  of  the  Declaration  of  
Helsinki,   the   applicable   ICH   guidelines   for   good   clinical   practices,   and   the   applicable  
federal,  state,  and  local  laws,  rules,  and  regulations  relating  to  the  conduct  of  the  protocol.      
I  have  read  and  understand  the  information  in  the  Instructions  for  Use  (and/or  other  such  
pertinent  safety  information)  regarding  the  risks  and  potential  benefits.      
I  agree  to  inform  all  those  who  assist/collaborate  with  me  in  the  conduct  of  this  study  of  
their  responsibilities  and  obligations.    
Once  the  protocol  has  been  reviewed  and  approved  by  the  Institutional  Review  Board  
(IRB)  I  understand  that  any  change(s)  made  during  the  course  of  the  study  must  also  

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(first)  be  approved  by  the  IRB  prior  to  implementation,  except  when  such  modification  is  
made  to  remove  any  immediate  hazard(s)  to  the  subject(s).      
I   certify   that   I   and   the   study   staff   responsible,   have   received   the   requisite   training   to  
conduct  this  research  protocol.      
I  agree  to  maintain  adequate  and  accurate  records  in  accordance  with  the  University  of  
Miami  policies,  federal,  state  and  local  laws  and  regulations.      
I   agree   to   maintain   the   confidentiality   of   all   information   received   and/or   developed   in  
connection  with  this  protocol.  
	  
RANJITH	  RAMASAMY	  	  
	  
	  
Print  Name  of  Physician  
  
  
  
  
  
  
  
  
  
April  13,  2016  
  
Physician’s  Signature  
Date  
  
  
  
  
  
  
1.  
BACKGROUND  
	  
1.1  
Study  Disease    
	  
Erectile  Dysfunction(ED)  is  a  condition  with  an  inability  to  develop  or  maintain  an  
erection  of  the  penis  upon  sexual  stimulation.  It  occurs      in  association  with  aging,  
chronic  illnesses  and  various  modifiable  risk  factors.  Amongst  the  modifiable  risk  
factors,   ED   shares   the   most   common   risk   factors   with   Coronary   Artery  
Disease(CAD)  which  are  smoking,  hypertension  and  hyperlipidemia1.  Even  though  

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it  is  not  a  part  of  normal  aging,  it  is  seen  in  52%  men  in  the  age  group  40  to  70  
years,  with  a  higher  rate  in  the  men  more  than  70  years2.    
  
Penile   erections   are   as   a   result   of   an   interaction   of   the   normal   physiologic  
processes   involving   the   central   and   peripheral   nervous   system,   endocrine   and  
vascular  systems.  Any  imbalances  in  these  processes  will  lead  to  the  development  
of  ED.    
  
The  phases  of  erection  are,  
§   Dilation  of  the  arterioles  and  arteries  as  a  result  of  increased  blood  
flow.  
§   Trapping  of  incoming  blood  by  the  expanding  sinusoids.  
§   Compression  of  the  venous  plexuses  reducing  venous  outflow.  
  
  
§   Stretching   of   the   tunica   to   its   maximum   capacity,   occluding   the  
emissary  veins  and  decreasing  the  venous  outflow  to  a  minimum.  
§   Erections  occurs  
  
ED  can  be  classified  in  to  two  groups,  Organic  and  Psychogenic.  
  
Vasculogenic   ED   which   belongs   to   the   Organic   group,   can   be   either   due   to  
arteriogenic,  or  venogenic  or  mixed2.  
  
Arteriogenic  ED  is  caused  due  to  a  narrowed  lumen  due  to  increased  resistance  
of  the  arteries,  enhanced  basal  and  myogenic  tone  leading  to  vasoconstriction,  
and   endothelial   dysfunction   resulting   in   impaired   endothelium   dependent  
vasodilation.  
  
Venogenic  ED  occurs  mainly  due  to  failure  of  adequate  venous  occlusion.    
  
The  inadequate  venous  occlusion  can  be  due  to    
  
§   Development   of   large   venous   channels   draining   the   corpora  
cavernosa.  
§   Degenerative   disease   (old   age,   Diabetes)   or   penile   fracture  
(traumatic  injury  to  the  tunica  albuginea)  resulting  in  the  inadequate  
compression  of  the  veins.  
§   Alteration  in  the  structure  of  the  fibroelastic  components  resulting  in  
venous  leak.  
§   Acquired  venous  shunts.  

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1.2  
Study  Interventions  
	  
Renova-­ED  is  a  Linear  Shockwaves  (LISW)  device  which  incorporates  a  unique  
shockwave  transducer  operable  to  deliver  shockwaves  to  a  treated  region  confined  
to   a   narrow   rectangle.   Shockwaves   generation   follows   the   electromagnetic  
principle.    
	  
Linear   Shockwaves   (LISW),   as   a   treatment   for   ED   has   been   in   evaluation   in  
contemporary   medicine   (see   section   1.4).   It   has   been   in   use   for   the   last   three  
years.  
  
The  present  study  is  about  a  device  called  “Renova-­ED”,  in  which  shockwaves  are  
focused  onto  line  segments  for  improved  organ  coverage.  Shockwaves  produced  
by  "Renova-­ED"  are  aimed  at  the  left  and  right  corpora  cavernosa  and  the  crura.  
The  study  is  aimed  at  determining  the  safety  and  effectiveness  of  this  new  type  
LISW  in  the  relief  of  ED.  
  
1.3  
Rationale  
	  
LISW  has  been  known  to  bolster  angiogenesis  by  increasing  the  levels  of  vascular  
endothelial  growth  factor.    
  
Principal  mode  of  action  used  in  other  disease:  
  
Coronary  Artery  Disease:  Kikuchi  et  al.3  showed  significantly  improved  symptoms  
and   decreased   nitroglycerin   use   in   patient   who   had   a   coronary   artery   bypass  
grafting  and  were  suffering  from  stable  angina.  
  
  
Bone  Healing:  Haupt  et  al.4  showed  that  Low  intensity  shock  waves  treated  group  
showed  radiological  signs  of  faster  healing.    
  
Calcifying  tendinitis:  Rompe  et  al.5  showed  that  shock  wave  to  patient  suffering  
from  calcifying  tendinitis  showed  a  62.5%  partial  and  complete  disintegration  of  the  
the  deposits.  Moreover,  85%  of  the  patients  reported  improvement  at  24-­week  
follow  up  period.  
  
Diabetic  Foot  Ulcers:  Wang  et  al.6  showed  that  Extracoproral  Shock  Wave  Therapy  
(ESWT)  to  patients  with  diabetic  foot  ulcer  showed  complete  improvement  in  31%  

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and   partial   improvement   in   58%.   Moreover,   ESWT   showed   significantly   better  
clinical  results  and  local  blood  flow  perfusion,  higher  cell  concentration,  and  activity  
than  the        Hyperbaric  Oxygen  group.    
  
1.4  
Preliminary  Studies    
	  
Contemporary  literature  shows  two  important  studies  in  this  field  both  conducted  
by  Vardi  et  al7,8.    
    
The  efficacy  trial  study  published  in  2010  recruited  20  men  with  vasculogenic  ED  
and  were  given  serial  2  sessions  of  treatment  for  about  3  weeks  followed  by  3  –  
week   no   intervention   period.   At   1-­month   duration   there   was   a   significant  
improvement  in  their  erectile  function  measured  by  International  Index  of  Erectile  
Function   ED   (IIEF-­ED)   domain   scores (20.9   5.8   vs   13.5   4.1,   p   <   0.001).   This  
significant   result   was   consistent   at   6-­month   follow   up.   Moreover,   no   pain   or  
adverse  event  was  noted  during  the  follow-­up  period.  
  
The   second   randomized,   double-­blind,   sham   controlled   study   by   showed   that  
treatment   group   showed   better   outcome   than   control   group   measured   using  
International  Index  of  Erectile  Function-­Erectile  Function  domain  (mean  SEM  6.7  
0.9  vs  3.0  1.4,  p  0.0322)  at  the  first  follow-­up.  Additionally,  penile  hemodynamics  
improve   significantly   in   the   treatment   group   in   comparison   to   control   group 
(maximal  post-­ischemic  penile  blood  flow  8.2  vs  0.1  ml  per  minute  per  dl,  p  0.0001).  
2.  
HYPOTHESIS  
	  
2.1  
Alternate  Hypothesis  (HA):  
	  
Active  Treatment  groups  will  show  a  >2-­point  increase  in  the  IIEF-­EF  score  from  
baseline   for   mild   erectile   dysfunction,   and   >5   points   for   moderate   erectile  
dysfunction  and  will  show  significant  change.  
  
  
  
  
  

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2.2  
Null  Hypothesis  (HO):    
	  
There  is  no  difference  from  baseline  and  after-­treatment  in  Treatment  groups  for  
alleviating  ED  measured  using  IIEF-­EF  score.  
3.  
OBJECTIVES  
	  
3.1  
Primary  Efficacy  Objective  
	  
To   evaluate   change   of   IIEF-­EF   score9   from   baseline   to   follow-­ups   1,   3   and   6  
months’  post  treatment  (appendix  I).  
3.2  
Secondary  Objectives  
	  
To  study  sexual  activity  improvement  leading  to  optimal  penetration  at  follow-­ups  
according  to:  
  
SEP-­  Sexual  Encounter  Profile:  Questions  2  and  3  (appendix  II)  
GAQ-­  Global  Assessment  Questions  (appendix  III)  
EHS-­  Erection  Hardness  Score  (appendix  IV)  
4.  
STUDY  DESIGN  
4.1  
Accrual  goal  
  
A  total  of  80  patients  with  Vasculogenic  ED  meeting  the  eligibility  criteria  will  be  
recruited  from  the  Department  of  Urology  clinic.    
4.2  
Duration  of  Study  Participation  
	  
The  total  duration  of  the  study  will  be  for  7  months–  including  1-­month  pretreatment  
(washout)  followed  by  a  period  of  6  months’  follow-­up  after  the  treatment.  
5.  
STUDY  ENTRY  AND  ENROLLMENT  AND  WITHDRAWAL  
	  
5.1  
Study  Entry  
	  

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Study  entry,  as  used  in  this  protocol,  will  be  defined  as  a  subject  signing  informed  
consent.      Study   enrollment,   as   used   in   this   protocol,   will   be   defined   as   the  
investigator’s   confirmation   of   the   subject’s   eligibility   by   signing   an   eligibility  
checklist.      As   per   University   of   Miami   policy,   each   study   participant,   including  
participants  who  have  screened  failed,  who  signs  an  informed  consent  form  should  
be  entered  into  the  study  database.    
  
	  
5.2  
Enrollment  Procedure  
	  
Completed  and  signed  protocol-­specific  eligibility  checklist;;    
All  pages  of  the  original  signed  informed  consent  forms  (ICFs),  including  HIPAA  
Form  B;;    
Relevant  source  documents  or  medical  records  such  as:    subject  medical  history  
and  physical  exam,  admission  or  discharge  notes,  diagnostic  reports,  pathologic  
confirmation  of  diagnosis,  and  relevant  subject-­specific  written  communication.  
Documentation  from  the  Investigator  that  he/she  has  determined  the  subject  meets  
eligibility  criteria.    
	  
5.3  
Cancellation  Guidelines  
	  
The  following  are  reasons  for  withdrawal  of  subjects  from  the  study:  
  
§   A  subject  does  not  meet  the  eligibility  criteria;;  (the  subject  will  be  
considered  a  screen  failure).      
§   A  subject  withdraws  consent,    
§   A  subject  die’s  during  protocol  participation  from  causes  other  than  
the  study  treatment  (not  due  to  adverse  events)  or    
§   A  study  investigator  decides  the  subject  should  be  withdrawn  from  
the  study  (e.g.  subject  non-­compliance)    
  
Regardless  of  reason  for  withdrawal,  once  a  patient  has  been  randomized  to  an  
arm,  an  intention  to  treat  analysis  will  be  performed.    
  
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  48  hours.      

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6.  
PATIENT  SELECTION/ELIGIBILITY  CRITERIA  
6.1  
Inclusion  (Eligibility)  Criteria  
	  
•   The  patient  must  be  able  willing  and  able  to  provide  informed  consent.    
•   The  patient  is  a  male  between  >30  and  <80  years  of  age.  
•   The   patient   has   ED   of   Vasculogenic   origin   determined   by   penile   duplex  
ultrasound.  
•   The   patient   is   PDE5i   responsive,   meaning   he   is   able   to   achieve   and  
maintain  an  erection  under  the  effect  of  the  maximal  dosage  of  PDE5i.  
•   The  patient  has  been  in  a  stable  heterosexual  relationship  for  over  3  months  
prior  to  enrollment.  
•   A  minimum  of  2  sexual  attempts  per  month  for  at  least  one  month  prior  to  
enrollment  –  as  documented  by  the  Sexual  Health  Questionnaire  (SHIM).    
•   The  patient  is  suffering  from  erectile  dysfunction  lasting  for  over  6  months  
and  not  more  than  5  years  as  per  history  provided  by  patient.    
•   IIEF-­EF  score  between  11  and  25.    
•   Testosterone  level  300-­1000  ng/dL  within  1  month  prior  to  enrollment.  
•   A1C  level  ≤  7%  within  1  month  prior  to  enrollment.  
•   Patients  have  at  least  a  natural  tumescence  during  sexual  stimulation  (EHS  
score  ≥  1).  
	  
6.2  
Exclusion  (Eligibility)  Criteria  
	  
•   The  patient  is  currently  or  has  participated  in  another  study  within  the  past  
three  months,  that  may  interfere  with  the  results  or  conclusions  of  this  study.  
•   The  patient  is  under  judicial  protection  (prison  or  custody).    
•   The  patient  is  an  adult  under  guardianship.  
•   The  patient  refuses  to  sign  the  consent.    
•   History  of  radical  prostatectomy  or  extensive  pelvic  surgery  ever.  
•   Venous  leak.  
•   Past   radiation   therapy   of   the   pelvic   region   within   12   months   prior   to  
enrollment.  
•   Recovering  from  any  cancer  within  12  months  prior  to  enrollment.  
•   Neurological   disease   such   as   Alzheimers   or   Parkinsons   disease   which  
affects  erectile  function  at  the  discretion  of  the  investigator.    

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•   Psychiatric  diagnosis  or  medications  such  as  antidepressants  which  affects  
erectile   function   or   any   other   medications   at   the   discretion   of   the  
investigator.  
•   Anatomical  malformation  of  the  penis,  including  Peyronie's  disease.  
•   Testosterone  level  <300  or  >1000  ng/dL  within  1  month  prior  to  
enrollment.  
•   A1C  level  >  7%  within  1  month  prior  to  enrollment.  
•   The  patient  is  taking  blood  thinners  and  has  an  international  normalized  
ratio  >3.  
	  
	  
6.3  
Study  Population  
	  
80  heterosexual  males  suffering  from  Vasculogenic  ED.    
7.  
STUDY  DESIGN,  CLINICAL,  RADIOLOGICAL,  LABORATORY  AND  
SURGICAL  EVALUATIONS  
7.1  
Study  Design    
	  
This  is  a  prospective,  randomized,  clinical  study  aimed  to  evaluate  the  safety  and  
efficacy  of  the  two  treatment  schedules  on  symptomatic  ED  patients.  The  patients  
are  randomized  in  a  1:1  ratio  into  two  active  treatment  groups.  (Refer  section  18)  
	  
7.2  
Screening  Evaluations  and  Procedures  
	  
The  first  visit  of  the  patients  will  be  for  screening  and  medical  evaluation.  Patient’s  
medical  co-­medication  history  will  be  collected  and  documented  and  a  physical  
examination  will  be  performed.    
  
Previous  month’s  blood  test  results  will  be  reviewed  including  a  general  chemistry  
panel,  a  lipid  profile,  A1C  and  Testosterone  levels  during  chart  review.  
  
Patients  will  sign  an  informed  consent  and  will  answer  the  IIEF-­EF  questionnaire  
to  see  if  they  fit  the  criteria  for  enrollment.  In  case  they  meet  all  inclusion  criteria  
(and  do  not  meet  any  exclusion  criteria),  they  will  be  recruited  to  the  study.    
  

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Patients   who   have   been   using   PDE5-­i   in   the   last   4   weeks   will   report   on   their  
medicine  type  and  dosage,  and  this  data  will  be  recorded  in  their  files  (reported  
prior  to  consent  and  gathered  from  chart  review).    
  
	  
7.3  
Pre-­Treatment  Procedures  and  Evaluations    
	  
Upon  evaluating  the  inclusion/exclusion  criteria,  patients  will  be  recruited  to  the  
study  and  randomized  into  one  of  the  two  groups  in  a  1:1  ratio  (randomization  will  
be  performed  by  a  computer  software  maintained  by  the  Department  of  Urology).  
Patients  randomized  to  the  treatment  groups  will  be  instructed  to  stop  any  use  of  
PDE5i  for  4  weeks  prior  to  first  treatment  session  and  refrain  from  using  any  other  
ED  therapy  option  during  the  study.  They  will  be  instructed  to  undergo  a  PDE5i  
washout  period  of  4  weeks  prior  to  treatment  and  to  avoid  using  PDE5i  or  any  other  
ED  treatment  during  the  entire  study  duration  (shockwave  treatment  and  follow-­
ups).  After  the  washout  period  and  before  the  first  treatment  session,  patients  will  
answer  the  IIEF-­EF,  SEP  and  EHS  questionnaires  for  baseline  evaluation.    
  
  
	  
	  
7.4  
Treatment  Procedures    
	  
The  treatment  session  lasts  approximately  20  minutes  and  may  be  performed  in  
an  office  environment.  Treatment  is  applied  in  the  physician’s  office.  For  session  
and  treatment  details  (see  below)  
  

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During  the  treatment,  the  same  total  number  of  shocks  will  be  delivered  according  
to  the  two  treatment  schedules  as  follows:    
	  
Group  A:  
  
5   daily   sessions   within   a   week   (MTWThF),   in   which   720   shocks   of   treatment  
energy  will  be  applied  in  every  session  to  each  treated  region  (left  and  right  corpora  
cavernosa  and  crura).  
  
Group  B:    
  
Three  sessions  per  week  (MWF)  for  2  consecutive  weeks,  in  which  600  shocks  of  
treatment  energy  will  be  applied  in  every  session  to  each  treated  region  (left  and  
right  corpora  cavernosa  and  crura)    
	  

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Following   the   last   treatment   session,   each   patient   will   resume   his   baseline  
consumption  of  PDE5i,  in  terms  of  type  and  dose  of  drug,  for  the  remainder  of  
study  duration.  
	  
7.5  
Follow-­Up  Procedures  and  Evaluations:  
	  
Follow-­up  visits  will  be  conducted  at  month  1,  month  3  and  month  6  after  the  last  
treatment  session  and  shall  include:    
  
Measuring  IIEF-­EF,  GAQ,  SEP,  and  EHS  scores  of  patients  at  the  clinic  at  every  
follow-­up  visit      
  
Reporting  and  recording  adverse  events  at  every  follow-­up  visit.  
8.  
ADVERSE  EVENTS  
	  
8.1  
Expected  Adverse  Events    
	  
In  known  studies  where  LISW  was  used  for  treatment  of  ED,  there  have  been  no  
reported   adverse   events   (Ref.   2,   Ref.   3).   However   minimal   side   effects   like  
Transitory  reddening  of  the  skin,  pain  small  bruising  and  swelling  can  be  expected.  
  
8.2  
Serious  Adverse  Events    
	  
Serious  injury  or  death    
  
Any  adverse  event  (penile  hematoma  or  penile  fracture)  and  eventual  complication  
must  be  recorded  at  any  time  during  the  treatments  and  the  follow  up  visits,  and  
throughout  the  entire  study  duration.  Patients  will  be  instructed  to  alert  the  study  
investigator   by   telephone   of   any   side   effects   occurring   in   the   period   after   the  
treatment  and  until  the  study  end.    
  
For  Reporting  of  adverse  events  see  section  9    
	  

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9.  
DATA  AND  SAFETY  MONITORING  PLAN  
	  
The  study  investigators  will  report  to  a  surgeon  monitor  Dr.  Murugesan  Manoharan  
in  the  department  of  urology  (who  is  not  involved  in  the   study)  to  ensure  data  
quality  and  subject  safety.  The  investigators  will  conduct  continuous  reviews  of  the  
data   and   subject   safety,   keeping   track   of   the   number   of   subjects,   significant  
toxicities  in  accordance  with  the  protocol  and  observed  responses,  which  will  be  
discussed  at  research  committee  meetings.  All  grade  3-­5  adverse  events  (CTCAE  
v4.0),  regardless  of  association  with  the  LISW,  will  be  entered  into  study  database  
and  reviewed  at  research  committee  meetings.  In  addition,  all  adverse  reactions  
considered  “serious”  will  be  entered  into  research  database  and  reviewed  by  the  
Surgeon  monitor  on  an  ongoing  basis.  If  a  death  occurs  within  30  days  of  LISW  
treatment  and  is  determined  to  be  related  to  the  study,  the  investigators  will  notify  
the  Department  Chair  Dr.  Dipen  Parekh  within  1  business  day.  If  an  increase  in  the  
frequency  of  grade  3  or  4  adverse  events  is  noted  in  the  study,  a  report  will  be  
submitted  to  the  Department  Chair  Dr.  Dipen  Parekh  at  the  time  the  increased  rate  
is  identified.  If  at  any  time  the  principal  investigator  stops  enrollment  or  stops  the  
study  due  to  safety  issues,  the  Department  Chair  (Dr.  Dipen  Parekh)  will  be  notified  
within  1  business  day  and  a  formal  letter  will  be  sent  to  the  Department  Chair  (Dr.  
Dipen  Parekh)  to  be  received  within  10  business  days.    
10.   STATISTICAL  CONSIDERATIONS  
10.1   Primary  Study  Endpoints  
  
The  IIEF-­EF  questionnaire  (appendix  I)  was  chosen  as  the  primary  clinical  efficacy  
assessment   tool   in   this   study.   The   total   score   (range   0-­30)   will   be   used   for  
statistical  analysis.    
	  
10.2   Secondary  Endpoints  
	  
Sexual  activity  improvement  leading  to  optimal  penetration  at  follow-­ups  will  be  
done  according  to:  
  
SEP  2  &  3  at  follow-­ups  
GAQ  at  follow-­ups  
EHS  at  follow-­ups.  
  
Endpoint  Measurements:  using  CRF/questionnaire  analysis  

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10.3   Endpoint  definitions  
	  
IIEF-­EF  Questionnaire  see  appendix  I  
SEP  2  &  3  Questionnaire  see  appendix  II  
GAQ  Questionnaire  see  appendix  III  
EHS  Questionnaire  see  appendix  IV  
	  
10.4   Sample  size,  accrual  and  study  duration  
	  
TOTAL  SAMPLE  SIZE:  80  
TOTAL  ACCRUAL:  80    
ACCURAL  DURATION:  12  MONTHS  
STUDY  DURATION:  7  months  
	  
10.5   Statistical  Analysis  and  Power  calculation      
	  
The   average   and   standard   deviation   of   all   relevant   variables,   including  
demographic  and  baseline  characteristics,  primary  and  secondary  outcomes  will  
be  calculated.    
  
IIEF-­EF  and  EHS  scores  will  be  analyzed  using  ANOVA  with  repeated  measures  
throughout  the  study,  in  order  to  compare  the  trends  of  groups  A  and  B.  
  
GAQ,  SEP  and  success  rates  will  be  analyzed  and  compared  between  the  groups  
according  to  Fisher's  exact  test  in  each  of  the  endpoints.  The  statistical  significance  
will  be  set  at  P<0.05.        
    
Demographic   characteristics   such   as   age   and   ED   duration   will   be   compared  
between  groups  A  and  B  using  student's  test.  Other  demographic  characteristics,  
such   as   medical   background   and   risk   factors   will   be   compared   between   these  
groups  using  Fisher's  exact  test.  
  
A   sample   of   80   men   with   failing   scores   on   the   IIEF   SEP2   question   will   be  
randomized  1:1  into  one  of  two  arms  (low  intensity  or  high  intensity  treatment)  
using  a  permuted  random  block  algorithm.    We  hypothesize  that  following  placebo  
treatment  between  0  and  5%  of  men  will  pass  the  SEP2  question  and  at  least  35%  
of   men   treated   at   either   intensity   level   will   pass.   We   have   two   co-­primary  

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endpoints,  the  percentage  of  men  passing  after  low  intensity  and  high  intensity  
relative   to   placebo,   which   will   be   assessed   by   two   independent   Fisher’s   exact  
tests.    Each  of  these  tests  will  be  conducted  with  a  0.025  alpha  error  level  to  allow  
for  a  0.05  experiment  wide  type  I  error  rate.  Power  calculations  done  in  SAS  9.4  
suggest  that  with  40  men  randomized  into  each  group  we  will  have  at  least  85%  
power  to  detect  the  difference  between  a  5%  and  35%  response  rate.    So  long  as  
our  non-­compliance/drop-­out  rate  remains  above  10%  will  will  have  at  least  80%  
power  (see  Figure  1).  
    
  
  
Figure  1.  Sample  size  needed  for  80%  85%  and  90%  nominal  power  for  a  Fisher’s  
exact   test   with   alpha   =   0.025   (using   an   exact   conditional   distribution   with   the  
Walters  normal  approximation  method).  
  
10.6   Randomization:  
	  
	  
80  patients  will  be  randomized  1:1  to  treatment  groups  with  40  patients  each.  An  
online  based  randomization  tool  called  randomized.org  will  be  used.  This  will  be  
prepared  beforehand,  with  treatment  option  printed  on  the  paper  and  then  sealed  
in  an  envelope  (80  envelopes).  Each  would  have  Patients  ID  number  printed  out  
side  and  randomization  information  inside.  This  would  be  opened  after  a  patient  
has  signed  the  informed  consent  and  is  ready  to  receive  treatment.  The  PI  nor  the  
study   coordinator   will   not   have   the   knowledge   of   patient’s   treatment   group  
beforehand.  
11.   INVESTIGATORS  RESPONSIBLITIES  
11.1   Investigator  Responsibility/Performance  
	  

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The  investigator  (or  a  person  designated  by  the  investigator)  should  inform  the  
patient  of  all  pertinent  aspects  of  the  study,  including  the  written  information.  
  
The  investigator  should  provide  the  patient  ample  time  and  opportunity  to  inquire  
about  details  of  the  study  and  to  decide  whether  or  not  to  participate  in  the  study.    
All  questions  about  the  study  should  be  answered  to  the  satisfaction  of  the  patient.  
Neither  the  investigator,  nor  the  study  staff,  should  coerce  or  unduly  influence  a  
patient  to  participate  or  to  continue  to  participate  in  a  study.  
  
11.2   Confidentiality  
	  
The  identity  of  the  patients  in  this  study  will  be  treated  as  confidential.  Patients  
eligible  to  participate  in  the  study  following  the  pre-­treatment  visit  will  be  assigned  
a  unique  patient  code.  The  results  of  the  study,  including  any  other  data,  may  be  
published  for  scientific  purposes  but  will  not  give  the  patients'  name  or  include  any  
identifiable  references  to  them.  
  
However,  any  records  or  data  obtained  as  a  result  of  the  patient  participation  in  
this  study  may  be  inspected  by  the  sponsor,  by  any  relevant  governmental  agency,  
by   the   Hospital   Ethics   Committee,   or   by   the   persons   conducting   this   study,  
provided   that   such   inspectors   are   legally   obligated   to   protect   any   identifiable  
information  from  public  disclosure,  except  where  disclosure  is  otherwise  required  
by  law  or  a  court  of  competent  jurisdiction.  These  records  will  be  kept  private  in  so  
far  as  permitted  by  law.    
	  
11.3   Informed  Consent  and  Permission  to  Use  Protected  Health  Information    
	  
It  is  the  responsibility  of  the  investigator  to  obtain  written  informed  consent  from  
each  subject  participating  in  this  study  after  adequate  explanation,  in  lay  language,  
of  the  methods,  objectives,  anticipated  benefits,  and  potential  hazards  of  the  study.    
The  investigator  must  also  explain  that  the  subject  is  completely  free  to  refuse  to  
enter  the  study  or  to  discontinue  participation  at  any  time  (for  any  reason)  and  
receive  alternative  conventional  therapy  as  indicated.    Prior  to  study  participation,  
each  subject  will  sign  an  IRB  approved  informed  consent  form  and  receive  a  copy  
of  same  (and  information  leaflet,  if  appropriate).    
  
The  investigator  or  designee  must  explain  to  the  subject  before  enrollment  into  the  
study  that  for  evaluation  of  study  results,  the  subject’s  protected  health  information  

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obtained   during   the   study   may   be   shared   with   the   study   sponsor,   regulatory  
agencies,   and   the   IRB.      It   is   the   investigator’s   (or   designee’s)   responsibility   to  
obtain   permission   to   use   protected   health   information   per   HIPAA   from   each  
subject,  or  if  appropriate,  the  subjects’  parent  or  legal  guardian.  
	  
11.4   Source  Documentation  and  Investigator  Files  
	  
The   investigator   will   maintain   adequate   and   accurate   records   to   document   the  
conduct  of  the  study  and  to  ensure  that  study  data  can  be  subsequently  verified.    
These  documents  will  be  classified  into  two  separate  categories:  (1)  investigator  
study  file  and  (2)  subject  clinical  source  documents  that  corroborate  data  collected  
on   the   CRF’s.      Subject   clinical   source   documents   would   include   hospital/clinic  
patient   records;;   physician's   and   nurse's   notes;;   original   laboratory,   radiology,  
pathology,  and  special  assessment  reports;;  QOL  forms,  signed  informed  consent  
forms.    When  the  CRF  or  any  form  is  used  as  the  source  document,  this  will  be  
clearly  stated  in  the  investigator  study  file.  
  
At  a  minimum,  the  following  be  documented  in  source  documents:  
  
•   Medical   history/physical   condition   and   diagnosis   of   the   subject   before  
involvement  in  the  study  sufficient  to  verify  protocol  entry  criteria.  
•   Study   number,   assigned   subject   number,   and   verification   that   written  
informed  consent  was  obtained  (each  recorded  in  dated  and  signed  notes  
on  the  day  of  entry  into  the  study)  
•   Progress  notes  for  each  subject  visit.  
•   Laboratory  test  results.  
•   Condition  and  response  of  subject  upon  completion  of  or  early  termination  
from  the  study.  
•   Quality  of  Life  Surveys.  
	  
11.5   Recording  and  Processing  of  Data  
	  
Data  for  this  study  will  be  entered  into  electronic  CRFs  in  research  database  (a  
web-­based   clinical   research   management   application).      A   CRF   is   required   for  
every  patient  who  received  any  study  intervention.    The  investigator  will  ensure  
that  the  CRF’s  are  accurate,  complete,  legible  and  timely.  Separate  source  records  
are  required  to  support  all  CRF  entries.    All  corrections  to  study  data  will  be  made  
by  drawing  a  single  line  through  the  information  to  be  corrected  without  obscuring  

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it.    All  corrections  will  be  initialed,  dated  and  explained,  if  necessary.  Do  not  use  
“white-­out”  or  obscuring  correction  tape.      
	  
11.6   Non-­Protocol  Research  
	  
No   investigative   procedures   other   than   those   described   in   this   protocol   will   be  
undertaken  on  the  enrolled  subjects  without  the  agreement  of  the  IRB.  
  
11.7   Ethics  
	  
The   investigator   agrees   to   conduct   the   study   in   compliance   with   the   protocol,  
current  good  clinical  practices,  and  all  applicable  (local,  FDA)  regulatory  guidelines  
and  standard  of  ethics  
  
11.8   Essential  Documents  for  the  conduct  of  a  clinical  trial  
	  
Essential  documents  are  those  documents  with  individually  and              collectively  
permit  evaluation  of  the  conduct  of  a  trial  and  the  quality  of  the  data  produced.  
  
The  following  documents  will  be  on  file:  
  
•   CV’s  and  license  of  all  investigators.  
•   IRB  documentation/correspondence.  
•   Documentation  of  IRB  certification.  
	  
12.   Appendix  I  International  Index  of  Erectile  Function  (IIEF  –  EF)  
Questionnaire.  9  
	  
	  
Name:	  	  
Date:	  
Write	  the	  number	  that	  best	  describes	  your	  erectile	  function	  for	  the	  past	  4	  weeks	  in	  the	  
spaces	  provided	  
Over	  the	  past	  four	  weeks:	  	  
1.	  How	  often	  were	  you	  able	  to	  get	  an	  
erection	  during	  sexual	  activity?	  
0	  =	  No	  sexual	  activity	  
1	  =	  Almost	  never/never	  
2	  =	  A	  few	  times	  (much	  less	  than	  half	  the	  

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time)	  
3	  =	  Sometimes	  (about	  half	  the	  time)	  
4	  =	  Most	  times	  (much	  more	  than	  half	  the	  
time)	  
5	  =	  Almost	  always/always	  
2.	  When	  you	  had	  erections	  with	  sexual	  
stimulation,	  how	  often	  were	  your	  erections	  
hard	  enough	  for	  penetration?	  
0	  =	  No	  sexual	  activity	  
1	  =	  Almost	  never/never	  
2	  =	  A	  few	  times	  (much	  less	  than	  half	  the	  
time)	  
3	  =	  Sometimes	  (about	  half	  the	  time)	  
4	  =	  Most	  times	  (much	  more	  than	  half	  the	  
time)	  
5	  =	  Almost	  always/always	  
3.	  When	  you	  attempted	  sexual	  intercourse,	  
how	  often	  were	  you	  able	  to	  penetrate	  
(enter)	  your	  partner?	  
0	  =	  Did	  not	  attempt	  intercourse	  
1	  =	  Almost	  never/never	  
2	  =	  A	  few	  times	  (much	  less	  than	  half	  the	  
time)	  
3	  =	  Sometimes	  (about	  half	  the	  time)	  
4	  =	  Most	  times	  (much	  more	  than	  half	  the	  
time)	  
5	  =	  Almost	  always/always	  
4.	  During	  intercourse,	  how	  often	  were	  you	  
able	  to	  maintain	  your	  erection	  after	  you	  
had	  penetrated	  (entered)	  your	  partner?	  
0	  =	  Did	  not	  attempt	  intercourse	  
1	  =	  Almost	  never/never	  
2	  =	  A	  few	  times	  (much	  less	  than	  half	  the	  
time)	  
3	  =	  Sometimes	  (about	  half	  the	  time)	  
4	  =	  Most	  times	  (much	  more	  than	  half	  the	  
time)	  
5	  =	  Almost	  always/always	  
5.	  During	  sexual	  intercourse,	  how	  difficult	  
was	  it	  to	  maintain	  your	  erection	  to	  
completion	  of	  intercourse?	  
0	  =	  Did	  not	  attempt	  intercourse	  
1	  =	  Extremely	  difficult	  
2	  =	  Very	  difficult	  
3	  =	  Difficult	  
4	  =	  Slightly	  difficult	  
5	  =	  Not	  difficult	  
15.	  How	  would	  you	  rate	  your	  confidence	  
that	  you	  could	  get	  and	  keep	  an	  erection?	  
1	  =	  Very	  low	  
2	  =	  Low	  
3	  =	  Moderate	  

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4	  =	  High	  
5	  =	  Very	  high	  
	  
	  
	  
	  
13.   Appendix  II  Sexual  Encounter  Profile  (SEP-­  Questions  2  and  3)10  
	  
SEP-­Q2:    Over  the  past  4  weeks,  were  you  able  to  insert  your  penis  into  your  partner's  
vagina?  
Yes………                                                                                No………  
SEP-­Q3:  Over  the  past  4  weeks,  did  your  erection  last  long  enough  for  you  to  have  
successful  intercourse?  
Yes………                                                                                No………  
14.   Appendix  III  Global  Assessment  Question  (GAQ)10  
	  
GAQ-­Q1:  Over  the  past  4  weeks,  has  the  treatment  you  have  been  taking  improved  
your  erectile  function?  
  
Yes………                                                                                No………  
GAQ-­Q2:  If  yes,  has  the  treatment  improved  your  ability  to  engage  in  sexual  activity  
over  the  past  4  weeks?  

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Yes………                                                                                No………  
15.   Appendix  IV  EHS-­  Erection  Hardness  Score.11  
	  
How  would  you  rate  the  hardness  of  your  erection?  
•   0:  Penis  does  not  enlarge  
•   1:  Penis  is  larger  but  not  hard  
•   2:  Penis  is  hard  but  not  hard  enough  for  penetration  
•   3:  Penis  is  hard  enough  for  penetration  but  not  completely  hard  
•   4:  Penis  is  completely  hard  and  fully  rigid  
	  
16.   List  of  Abbreviations  
	  
ED	  
Erectile	  Dysfunction	  
AE	  
Adverse	  Event	  
EHS	  
Erection	  Hardness	  Score	  
GAQ	  
Global	  Assessment	  Questions	  
IIEF-­‐‑EF	  
The	  International	  Index	  of	  Erectile	  Function	  –	  Erectile	  Function	  
LISW	  
Low	  Intensity	  Shock	  Wave	  
PDE5i	  
Phosphodiesterase	  type	  5	  inhibitor	  
SEP	  
Sexual	  Encounter	  Profile	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  

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17.   Study  Calendar  
	  
	  
	  
	  
	  
	  
	  
	  
          Visit #, Time 
 
 
 
 
Activity 
Visit 1 
Screening 
Visit 2 
Pre-Treatment 
Week 1  
Visits 3-7 
 5 Treatment 
sessions
Week 1  
Visits 3-5 
 3 Treatment 
sessions
Week 2  
Visits 6-8 
 3 Treatment 
sessions 
Visit 8/9 
1 Mo FU 
Visit 9/10 
3  Mo FU 
Visit 10/11  
6  Mo FU 
Medical & 
Urological History 
●	  
	  
	  
	  
	  
	  
	  
 
Physical 
Examination 
●	  
	  
	  
	  
	  
	  
	  
 
Informed Consent 
●	  
	  
	  
	  
	  
	  
	  
 
Inclusion & 
Exclusion Criteria 
●	  
	  
	  
	  
	  
	  
	  
 
IIEF-EF, GAQ, 
SEP, EHS 
●	  
	  
	  
	  
	  
●	  
●	  
● 
Study Recruitment  
& Group 
Randomization 
	  
●	  
	  
	  
	  
	  
	  
	  
Record Treatment 
Parameters 
	  
	  
Group	  
A	  
Group	  
B	  
Group	  B	  
●	  
●	  
●	  
Report 
Complications 
	  
	  
●	  
●	  
●	  
●	  
●	  
●	  

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18.   Study  Design  Flowchart:  
	  
	  
	  
ED patients (80) 
Week 1 - 
5 treatments  
Week 1 - 
3 treatments  
1 Mo follow-up 
Week 2 - 
3 treatments 
3 Mo follow-up 
6 Mo follow-up 
1 Mo follow-up 
Group A(40) 
Group B (40) 
3 Mo follow-up   
6 Mo follow-up   

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19.   References:  
	  
1. 
Vlachopoulos C, Rokkas K, Ioakeimidis N, et al: Prevalence of Asymptomatic 
Coronary Artery Disease in Men with Vasculogenic Erectile Dysfunction: A 
Prospective Angiographic Study. European Urology 2005; 48: 996–1003. 
2. 
MELMAN A and GINGELL JC: THE EPIDEMIOLOGY AND 
PATHOPHYSIOLOGY OF ERECTILE DYSFUNCTION. The Journal of Urology 
1999; 161: 5–11. 
3. 
Kikuchi Y, Ito K, Ito Y, et al: Double-Blind and Placebo-Controlled Study of the 
Effectiveness and Safety of Extracorporeal Cardiac Shock Wave Therapy for 
Severe Angina Pectoris. Circulation Journal 2010; 74: 589–591. 
4. 
Haupt G, Haupt A, Ekkernkamp A, et al: Influence of shock waves on fracture 
healing. Urology 1992; 39: 529–532. 
5. 
Rompe JD, Rumler F, Hopf C, et al: Extracorporal Shock Wave Therapy for 
Calcifying Tendinitis of the Shoulder. Clinical Orthopaedics and Related Research 
1995; 321: 196. 
6. 
Wang C-J, Kuo Y-R, Wu R-W, et al: Extracorporeal shockwave treatment for 
chronic diabetic foot ulcers. J. Surg. Res. 2009; 152: 96–103. 
7. 
Vardi Y, Appel B, Jacob G, et al: Can low-intensity extracorporeal shockwave 
therapy improve erectile function? A 6-month follow-up pilot study in patients with 
organic erectile dysfunction. European Urology 2010; 58: 243–248. 

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8. 
Vardi Y, Appel B, Kilchevsky A, et al: Does low intensity extracorporeal shock 
wave therapy have a physiological effect on erectile function? Short-term results 
of a randomized, double-blind, sham controlled study. The Journal of Urology 
2012; 187: 1769–1775. 
9. 
Rosen RC, Riley A, Wagner G, et al: The international index of erectile function 
(IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 
1997; 49: 822–830. 
10. 
Agency for Healthcare Research and Quality (AHRQ): Diagnosis and Treatment 
of Erectile Dysfunction. In: Diagnosis and Treatment of Erectile Dysfunction. 
2009; pp 1–770. 
11. 
Mulhall JP: Defining and reporting erectile function outcomes after radical 
prostatectomy: challenges and misconceptions. The Journal of Urology 2009.