Prostate Embolization for Benign Prostatic Hyperplasia
Phase: PHASE1
Conditions: Benign Prostatic Hyperplasia
Sponsor: James B. Spies, MD

 
 
 
 
 
PROSTATE EMBOLIZATION FOR BENIGN PROSTATIC HYPERPLASIA (BPH) 
 
NCT:1924988 
 
Approved by the Georgetown University Institutional Review Board 
6/20/2013 
[Type the abstract of the document here. The abstract is typically a short summary of the contents of the 
document. Type the abstract of the document here. The abstract is typically a short summary of the contents of 
the document.] 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
1 
Georgetown University Institutional Review Board Application (Protocol) for Biomedical IRB Review (AB-
1) 
 
Section One: Application Information 
 
Principal Investigator: 
James B. Spies, MD 
 
Department: 
Radiology 
 
Title: 
Professor and Chair 
 
Phone/Pager: 
202-444-3450 / 202-405-3733 
 
Fax: 
202-444-4899 
 
E-mail address: 
spiesj@gunet.georgetown.edu 
 
Mailing Address: 
3800 Reservoir Road NW, CG 201, Washington, DC 20007-2113 
 
Co-Investigator: 
John Lynch, MD 
 
Department: 
Urology 
 
Title: 
Professor and Chair 
 
Phone/Pager: 
202-444-2707 
 
Fax: 
202-444-7573 
 
E-mail address: 
lynchj@gunet.georgetown.edu 
 
Mailing Address: 
3800 Reservoir Road NW, PHC1, Washington, DC 20007-2113 
 
Responsible Participant (member of 
faculty or official or administrative unit) 
James B. Spies MD 
 
Title: 
Professor and Chair 
 
Phone/Pager: 
202-444-3450 / 202-405-3733 
 
E-mail address: 
spiesj@gunet.georgetown.edu 
Research Nurse Assigned: 
 
 
Phone/Pager: 
 
 
E-mail address: 
 
Study or Data Coordinator: 
 
 
Phone/Pager: 
 
 
E-mail address: 
 
Biostatistician (If study is Institutional) 
 
 
Phone: 
 
 
Title of Project 
Purpose of Project (one or two sentences) 
 
Prostate Embolization for Benign Prostatic 
Hyperplasia  
 
This is a Phase I/II study with the primary goal of 
determining the safety of prostatic artery embolization (PAE) 
for benign prostatic hypertrophy. Our primary outcome is the 
frequency of adverse events, particularly bladder and rectal 
complications, which may occur as a result of this procedure. 
Secondarily, the study will allow us to begin to determine its 
effectiveness in diminishing obstructive symptoms associated 
with BPH. 
 
 
Additional Co-Investigators/Consultants, if any Department or Institution 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
2 
Justin Lee, MD 
Department of Radiology 
Keith Kowalczyk MD 
Department of Urology 
 
Estimated duration of total project 
 
12 month recruitment, 5 year follow-up 
Estimated total number of subjects  
(including control subjects) 
30 
 
Age range of subjects 
40 - 99 
 
Sex of subjects 
Male 
 
Where will study be conducted? 
Georgetown University Hospital 
 
Source of subjects 
Georgetown University Hospital, Depts. of Radiology and 
Urology 
Experience of Principal Investigator: 
Brief summary (also attach a CV, 
biosketch, or Form 1572, if available ) 
Dr. Spies is an internationally known researcher in embolization, 
particularly of uterine fibroids. His group has performed over 
3000 uterine embolization procedures. He has a long history in 
managing both single center and multi-center clinical studies in 
embolization. He has performed similar PhaseI1 and II studies in 
uterine embolization and his initial 1997 Georgetown IRB 
protocol for uterine embolization was the first such protocol in 
the country. He has long experience in safety studies, having 
studied the complication rates of the first 400 uterine 
embolization patients treated here and also as a co-investigator on 
the FIBROID Registry, a 3000 patient safety and efficacy 
registry. 
 
Dr. Spies has visited centers in both Lisbon, Portugal and Sao 
Paulo, Brazil and has observed approximately 20 prostate 
embolization procedures during those visits. He also performed a 
prostate embolization under the tutelage of Dr. Francisco 
Carnevale at the University of Sao Paulo 
 
Source of Funding/Grant Support for Project (if any) 
Please attach two copies of the Grant Application 
Commercial Support (if any) for Project 
None 
 
 
 
 
 
 
Has this study undergone previous scientific review?  
Please note that independent scientific review and approval are required for all DOD sponsored studies. 
 
 Yes  
 
 No 
 
If yes, state where reviewed and attach documentation of approval 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
3 
 
 
 
Investigational New Drug (IND) 
 
 None 
 IND: FDA # ________________ 
 Drug Name:    
 
___________________________________ 
 Drug Sponsor: 
 
___________________________________ 
 Significant (SR)     
 Non-Significant Risk (NSR) 
 
Investigational Device Exemptions (IDE) 
 
None 
X  IDE: FDA No.    G120220/A00 
X  Device Name:      
 
Embospheres Microspheres 
 Device Sponsor:   
 
___________Investigator sponsored_____ 
X  Significant (SR)     
 Non-Significant Risk (NSR) 
If this project involves an FDA regulated drug or device, you must file an FDA form 3455.  
Please submit any communications from the FDA regarding IND, IDE, or humanitarian use applications 
related to this submission. 
 
Phase I/II 
Phase:  I 
  
 II 
    III 
    IV
    Pilot 
 
 
Section Two: Additional Georgetown University Regulatory Information 
 
1. 
Does this project involve the use of biohazardous materials, recombinant DNA and/or gene therapy? If so, 
Institutional Biosafety Committee (IBC) approval must be obtained. Contact (202) 687-4712 for assistance. 
 Yes  
 
 No 
 
Has the Institutional Biosafety Committee approved the protocol? 
 
Approved 
Date Approved: 
Application Pending 
Date Submitted: 
 
2. 
Does this project include the use of radioisotopes and/or radiation-producing devices regardless of whether 
the use is incidental to the project? If so, all protocols must be submitted to the GUH RSC along with a 
completed Form_0.30 for Radioactive or Form_0.31 for X-Rays. The forms require information on the use of 
radioisotopes and radiation-producing devices and must include dose calculations. Forms are on the IRB 
website: http://www.georgetown.edu/gumc/ora/irb/irbForms.htm  or call 202-444-4657 to obtain forms or if 
additional information is required. 
 Yes  
 
 No 
 
Has the Radiation Safety Committee approved the protocol? 
 
Approved 
Date Approved: 
 Application Pending 
Date Submitted: 
 
3. 
Does this project involve the use of fetal tissue? 
 Yes  
 
 No 
 
4. 
Do any investigators or co-investigators have a conflict of interest as defined in the Georgetown University 
Faculty handbook? http://www.georgetown.edu/facultysenate/handbook.html#financial  
 Yes  
 
 No 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
4 
 
A copy of the current Conflicts of Interest Disclosure Form for each Investigator and Co-Investigator involved 
with this study must be attached to this application. 
 
 
Section Three: Information for Protocol Review 
Please answer each specific question and use additional sheets as needed. A response of “See attached protocol 
or grant application” is not sufficient. 
 
5. 
Study Description (summarize the protocol according to the following format in less than 2 total pages) 
 
Study Design (for example, hypothesis, research question, standard and experimental procedures, special or 
unusual equipment or procedures) : 
 
This study will assess if embolization of the prostate can produce symptomatic improvement for patients with 
lower urinary tract symptoms as a result of benign prostatic hyperplasia. It will be managed by personnel of the 
Interventional Radiology Section of the Department of Radiology and members of the Urology department 
of of Georgetown University Hospital. 
Rationale and justification for study (for example, historical background, investigator’s personal experience, 
pertinent medical literature): 
 
Benign prostatic hyperplasia is a highly prevalent condition in which there is nodular growth of prostatic tissue, 
enlarging the prostate and narrowing the urethra. It may result in symptoms of lower urinary tract obstruction 
including hesitancy, intermittent voiding, weakened urinary stream, incomplete emptying, and post-void 
leakage.  The pathophysiology of BPH-induced obstruction includes mechanical and dynamic components.  
The mechanical component consists of tissue invasion into the urethral lumen or bladder neck.  The dynamic 
component results from adrenergic tone on the smooth muscle within the stroma.  Both these components 
contribute to an increase in urinary outflow resistance. 
 
Current medical management of BPH includes two classes medications that target the dynamic and stable 
aspects of prostatic obstruction; α-adrenergic blockers and 5α-reductase inhibitors respectively. The α-
adrenergic blockers directly inhibit sympathetic tone, which relaxes the smooth muscle of the prostate.  The 5α-
reductase inhibitors (including Finasteride) prevent conversion of testosterone to dihydrotestosterone, which is 
the chief hormone promoting stromal and epithelial proliferation in the prostate.  Over the course of a year, this 
can decrease peri-urethral prostate size and relieve obstruction. 
 
Anti-cholinergics are another class of medications used to ameliorate lower urinary obstructive symptoms. The 
urinary bladder contracts when muscarinic receptors on smooth muscle are stimulated by acetylcholine.  While 
these drugs do not benefit patients with symptoms secondary to BPH, some of these patients may in fact have 
co-incident bladder dysfunction and anticholinergic medications may prove beneficial [1]. 
Surgical therapy is reserved for patients exhibiting moderate to severe symptoms not controlled by medical 
therapy or in patients who refuse or do not tolerate the treatment.  Traditionally open prostatectomy was the 
surgical option of choice, but with onset of new surgical techniques and technologies open prostatectomy is 
typically reserved for larger (usually >80-100g) prostates. Open prostatectomy may also be recommended when 
there is a concomitant bladder diverticulum or bladder stone. 
The current gold standard of surgical options is transurethral resection of the prostate (TURP). This procedure 
focuses on resecting peri-urethral prostatic tissue, which is most contributory to static obstruction.  
Complications of TURP include significant bleeding, TUR syndrome (hyponatremia secondary to absorption of 

Georgetown University Institutional Review Board 
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5 
hypotonic irrigant), retrograde ejaculation, and urinary incontinence.  Given these potentially serious adverse 
events, several new techniques have been developed, yet a recent systematic review noted that there is little 
evidence any are more efficacious than TURP and as such it remains the gold standard [2]. Some of these 
newer approaches include transurethral incision of prostate, which is reserved for men with obstruction and 
small prostates. This procedure is more rapid than TURP and outcomes in well-selected patients are equivalent 
to that of TURP with less morbidity from bleeding, TUR syndrome, and rate of retrograde ejaculation [3]. 
Several different techniques of laser surgery for the prostate have been described, the two main energy sources 
are Nd:YAG and holmium:YAG. These procedures can be performed under direct visualization or with 
transrectal ultrasound guidance.  Laser ablation is particularly useful in patients on anticoagulation as bleeding 
risk is minimal.  Similar to other coagulative techniques, the prostatic urethra is not immediately 
excised/resected; instead it is sloughed off over the course of a few weeks. Studies suggest that patients 
undergoing Holmium laser enucleation require shorter hospitalization, experience decreased blood loss, and 
have similar outcomes to TURP at the expense of increased procedure time [4]. Yet, despite these considerable 
attempts at innovation in the field, none of these technologies has been sufficiently effective to displace TURP. 
Pelvic Embolization 
Non-selective hypogastric artery embolization was originally described as a management option for refractory 
hematuria in 1974 [5] and was subsequently reported in case reports as an emergency treatment for refractory 
hematuria secondary to BPH, adenocarcinoma of the prostate, and post-operative/post-biopsy bleeding [6] [7]. 
Over the past 3 decades there have been a number of case reports and small case series that have been 
published regarding embolization of pelvic tumors, including prostate and bladder cancer, and for bleeding 
after transurethral resection of the prostate. These findings are summarized in the table below. 
 
Table 1. Reports of embolization for bladder or prostate bleeding 
Study 
Pathology 
# of 
patients 
Embolic 
Control of 
hemorrhage 
Major 
Complications 
Hald et al 
1974 [5] 
Bladder hemorrhage 1 
 
Yes 
None 
Mitchell et al 
1976 [6] 
Prostate cancer, 
Post-TURP 
Bleeding 
4 
 
Yes 
None 
Russinovich 
1979 [7] 
Post-TURP 
bleeding 
1 
Gelfoam 
Yes 
None 
Faysal et al 
1979  
Post-TURP 
bleeding 
1 
 
Yes 
None 
Appleton et al 
1988 [8] 
Bladder hemorrhage 
Prostate 
hemorrhage 
8 bladder 
2 prostate 
 
Yes for prostate 
Yes for 4 of 6 
bladder 
None 
Suzuki et al 
1998 [9] 
Post-TURP 
bleeding 
1 
Cyanoacrylate 
and coils 
Yes 
None 
Barbieri et al 
2002 [10] 
Post-TURP 
bleeding 
1 
 
Yes 
None 
Michel et al 
2002 [11] 
Post-TURP 
bleeding 
1 
Cyanoacrylate Yes 
None 
Nabi et al 
2003 [12] 
Prostate cancer  
Bladder cancer 
3 prostate 
3 bladder 
Coils in the 
hypogastric 
artery 
Yes 
None 
El-Assmy et al Bladder hemorrhage 7 
Alcohol and 
Yes, recurrence 
None 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
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6 
2007 [13] 
microcoils 
in 3 
Rastinehad et 
al 2008 [14] 
CA of the prostate 
Post-TURP 
bleeding 
6 
2 
PVA or 
TAGM 
Yes, recurrence 
in 1 cancer 
patient 
Rectal-vaginal 
fistula in cancer 
patient 
Tan et al 2009 
[15] 
Post-TURP 
bleeding 
1 
 
 
 
Liguori et al 
2010 [16] 
Cancer of bladder, 
prostate, uterus, 
other cancers 
44 
PVA, PVA 
hydrogel 
spheres 
Yes in 81% 
Reduced 
bleeding in 
others 
None 
Delgal et al 
2010 [17] 
Bladder hemorrhage 
/Prostate 
hemorrhage 
20 
PVA or 
TAGM 
Yes in 90% 
None 
Jeong et al 
2010 [18] 
Hemorrhage after 
radical 
prostatectomy 
4 
Enbucrylate 
and poppy oil 
Yes 
None 
 
In total, there are 130 patients reported in the case reports and studies listed above. All were pelvic 
embolizations, although with a wide range of pathologies. If one leaves out the study by Liguori [16], which 
included a variety of malignancies in the pelvis, all the other above cases, 86 in total, were for treatment of 
bleeding from the urinary tract due either to malignancy of the bladder or prostate or from bleeding after 
transurethral resection of the prostate. The use of a variety of embolics in these reports, in the setting of 
emergency treatment, without reported injury to the bladder or other pelvic organs suggests that there may be a 
margin of safety in the embolization of the prostate and bladder.  
Animal Studies of Prostate Embolization 
Several studies have since been performed to assess the safety and feasibility of prostatic embolization in 
animal models.  The earliest was an investigation published in 1980 by Darewicz [19]. Five dogs were 
catheterized and each internal iliac artery embolized with n-butyl-2-cyanoacrylate. This liquid embolic material 
results in complete occlusion of the vessels into which it is injected. After animal sacrifice, pathologic 
examination of the prostate tissue showed no macroscopic changes. Microscopic examination revealed 
infiltration of lympohocytes, histiocytes and fibroblasts in the interstitial tissue. No injuries to other pelvic 
organs were noted. 
A study on 16 healthy male pigs (randomly assigned to embolization or control) investigated sexual function 
after prostate embolization [20]. The treatment arm underwent embolization with 500-700 micron size tris-acryl 
gelatin microspheres (TAGM), (Embosphere® Microspheres, Biosphere Medical/ Merit Medical, South Jordan 
UT) of animal’s prostatic arterial supply, while the control group underwent prostate arteriography alone. 
Sexual function was evaluated in all the pigs by observation of mating behavior 3 months after the procedure 
and no difference was noted between the groups (p = 0.328). The animals were then sacrificed and the urinary 
bladder, ureters, vas deferens and urethra were normal in all. The treated animals’ prostate glands were smaller 
than the untreated (3.9 ml vs 7.3 ml, p <0.001) and pathologically demonstrated arteriolar thickening with 
leukocytic infiltration. There was peri-arteriolar fibrosis, with atrophy of the glandular tissue in most of the 
balance of the gland.   
In a study of prostate embolization in canines, benign prostatic hyperplasia was induced using hormones in 9 
beagle dogs [21]. The dogs underwent hormonal stimulation for either 12 or 24 weeks. Five of the 9 beagles 
were embolized, in all cases with 255-355 micron size polyvinyl alcohol particles (PVA), (Contour®, Boston 
Scientific, Natick, MA). Half the dogs were hormonally stimulated for 12 weeks and half for 24 weeks. All 
animals that were embolized (5 of the 9) were treated 12 weeks after the initiation of the hormones and were 
sacrificed 12 weeks after embolization (24 weeks after baseline). In the group stimulated for 24 weeks that 
were not embolized, there was evidence histologically of diffuse glandular hyperplasia with micro-cystic 

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change. Those stimulated for 24 weeks who were embolized showed gross evidence of cystic change and 
microscopically atrophied glands intermixed with islands of normal glandular hyperplasia. The embolic 
material was found in the periphery of the gland with inflammatory cell infiltration. Pathologic examination of 
the bladders showed one specimen with focal hemorrhage in the bladder wall, but not involving the entire 
thickness of the bladder. No other bladder injuries were reported. 
A similar study was reported in 2011, again using hormonal stimulation in 10 beagles for 3 months [22].  Seven 
of the ten were randomly selected for embolization with 300-500 micron size TAGM. The pathologic findings 
were similar to the study reported above. The embolized prostate glands showed gross cystic change and 
microscopic cysts lined with atrophied glands, compatible with major areas of glandular necrosis. There were 
no bladder injuries, but two animals were found to have a slight adhesion between the posterior surface of the 
prostate and the anterior wall of the rectum.  No mural or mucosal injuries to the rectum were reported. 
Animal studies in this setting have limitations. The beagle model does not replicate human BPH, symptom 
change cannot be assessed in animals, and objective improvement of urinary flow also cannot be measured, as 
the BPH model in canines does not induce bladder outlet obstruction. Also, most men who would be treated 
with this treatment are over 60 and many will have atherosclerosis. It is unclear if atherosclerosis limits 
collateral flow to the pelvic organs and what role this might play in bladder or rectal injuries. Therefore, while 
the animal studies provide useful data regarding tissue response and safety of embolization, human studies are 
needed to further clarify safety and effectiveness. 
Prostate embolization as a therapy for BPH in humans 
In 2000 DeMeritt reported a case describing selective prostatic embolization utilizing 150-200µm PVA 
particles in a 76 year old patient with refractory hematuria and severe lower urinary tract symptoms (LUTS) 
secondary to BPH [23].  The gross hematuria resolved immediately after the procedure and follow-up at 12 
months demonstrated a significant reduction in his LUTS as measured by the IPSS (24 to 13).  Further, there 
was a 40% reduction in prostate volume and a decrease in PSA from 40ng/ml to 4ng/mL.  Aside from a 
transient post-operative fever, there were no complications in that patient.  
Recently there have been several small clinical trials on patients with BPH refractory to medical management. 
In Brazil, Carnevale et al. performed PAE with 300-500µm TAGM on two patients with acute urinary retention 
secondary to BPH who were initially managed on α-blocker therapy and urethral catheterization [24].  One 
patient was treated with bilateral embolization while the other unilaterally.  Preliminary results with 6-month 
follow-up demonstrated a 39.7% reduction on US and 47.8% reduction on MRI in prostate volume from 
baseline in the bilaterally treated patient and 25.5% and 27.8% respectively in the unilaterally treated patient 
with no evidence of complications in either patient. Further follow-up at 18 months demonstrated interval 
increase in prostate size as measured by US and MRI in the unilaterally treated patient (19.6% and 12.2% 
reduction from baseline) while the bilaterally treated patient’s prostate volume remained stable (39.7% and 
53.6% reduction from baseline) relative to 6-month follow-up.  Both patients reported significant improvement 
in their IPSS and quality of life score at 18 months with the bilaterally treated patient reporting a score that 
decreased from 8 at 1 month follow-up to 1 while the unilaterally treated patient reported a decrease from 17 to 
7 [25].  
This group has recently presented its most recent results in a total of 12 patients, including the two discussed 
above, at the March 2012 Annual Meeting of the Society of Interventional Radiology [26]. All of these patients 
had catheter dependent urinary retention. The procedure was clinically successful in 10 patients. Patients had 
spontaneous urination after catheter removal a mean of 12 days post-treatment. While no major complications 
were noted, 3 of 12 had minimal rectal bleeding, 2 of 12 had diarrhea, and focal bladder ischemia in 1 of 12. 
Mean prostate volume reduction was 30% and most had significant improvement in IPSS and QOL scores. 
A clinical study with 15 patients performed in Portugal was published in early 2011 by Pisco et al. utilizing 
200µm non-spherical PVA particles (Cook Inc., Bloomington IN) [27].  Technical success, defined as selective 
prostatic arterial embolization of at least one pelvic side, was achieved in 14 of 15 patients. Bilateral 
embolization was achieved in 13 patients, unilateral in 1 and embolization failed technically in one patient on 
both sides due to vessel tortuosity.  With a mean follow-up of 7.9 months Pisco et al. reported a decrease of 
IPSS by a mean of 6.5 points (p=.005), improved quality of life score by 1.14 (p=.065), an increase in erectile 

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function score by 1.7 points (p=0.63), a mean decrease in PSA by 2.27ng/mL (p=.072), and a mean prostate 
volume reduction by 26.5mL (p=.0001).  The authors reported a major complication in one patient that 
experienced severe intraoperative pain during embolization and was subsequently found to have a 1.5cm2 area 
of necrosis in the inferior bladder wall requiring surgical repair.  Of the 14 patients that were technically 
successfully treated, only 10 achieved clinical success (defined as an improvement of symptoms with an 
IPSS<20 and/or improvement of Qmax to greater than 7mL/sec). 
Pisco’s group also just presented the results of 152 patients at the same SIR meeting in March 2012 [28], 
although these results are not yet published. The procedure was technically successful in 144 of 152 patients. 
Follow-up of between 3 and 30 months was available in 102 patients. Clinical success was noted in 84.3% at 3 
months and in 38 of 46 (82.6%) at 12 months. These authors reported no major complications beyond the 
bladder wall ischemia noted in their initial published report. They did report a number of minor complications, 
although they did not report the frequency in the published abstract. These included burning in the urethra, 
urinary infection, hematuria, hemospermia, balanoprostatitis, rectorrhagia, inguinal hematoma and pain. 
These initial reports suggest that prostate embolization is feasible and the initial results suggest that 
improvement in symptoms occurs in the majority and that shrinkage in prostate volume is likely. The safety is 
somewhat less certain. While major complications are likely rare, it is unclear how frequently minor injuries to 
the bladder and rectal mucosa occur. We believe it is important to confirm the safety of this procedure in 
practice in a well-designed study in the US, with careful evaluation and follow-up of each patient prior to the 
development of a larger trial or acceptance of this procedure into practice. The materials used in these 
procedures have FDA clearance for other indications and are readily available for interventionalists to use in 
this treatment. To date there has been no clinical trial completed in the United States and we believe that an 
assessment of this treatment in clinical studies is essential before its adoption into practice. 
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1. 
Blake-James, B.T., et al., The role of anticholinergics in men with lower urinary tract symptoms 
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Lourenco, T., et al., Alternative approaches to endoscopic ablation for benign enlargement of the 
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Yang, Q., et al., Transurethral incision compared with transurethral resection of the prostate for 
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Tan, A., et al., Meta-analysis of holmium laser enucleation versus transurethral resection of the 
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Hald, T. and T. Mygind, Control of life-threatening vesical hemorrhage by unilateral hypogastric 
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Mitchell, M.E., et al., Control of massive prostatic bleeding with angiographic techniques. J Urol., 
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BJU international, 2003. 92(3): p. 245-7. 
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Jeon, G.S., et al., The effect of transarterial prostate embolization in hormone-induced benign prostatic 
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Sun, F., et al., Transarterial prostatic embolization: initial experience in a canine model. AJR Am J 
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23. 
DeMeritt, J.S., et al., Relief of benign prostatic hyperplasia-related bladder outlet obstruction after 
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Carnevale, F.C., et al., Prostatic artery embolization as a primary treatment for benign prostatic 
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Pisco, J.M., et al., Prostatic arterial embolization to treat benign prostatic hyperplasia. J Vasc Interv 
Radiol, 2011. 22(1): p. 11-9; quiz 20. 
28. 
Pisco, J.M., et al., Further evaluation of prostaic artery embolization of symptomatic benign prostatic 
hyperplasia in a large series of patients. Safety, sort and medium term outocmes., in Annual Meeting 
Society of Interventional Radiology2012: San Francisco. p. S34-S35. 
29. 
Jepsen, J.V. and R.C. Bruskewitz, Comprehensive patient evaluation for benign prostatic hyperplasia. 
Urology, 1998. 51(4A Suppl): p. 13-8. 
30. 
Bosch, J.L.H.R., et al., The International Prostate Symptom Score in a community-based sample of men 
between 55 and 74 years of age: prevalence and correlation of symptoms with age, prostate volume, 
flow rate and residual urine volume. British Journal of Urology, 1995. 75(5): p. 622-630. 
31. 
O’Leary, M.P., LUTS, ED, QOL: alphabet soup or real concerns to aging men? Urology, 2000. 56(5, 
Supplement 1): p. 7-11. 
32. 
Rosen, R.C., et al., The international index of erectile function (IIEF): a multidimensional scale for 
assessment of erectile dysfunction. Urology, 1997. 49(6): p. 822-30. 
33. 
Rosen, R.C., et al., Development and evaluation of an abridged, 5-item version of the International 
Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. International journal 
of impotence research, 1999. 11(6): p. 319-26. 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
10 
 
 
Primary study endpoint: 
 
Frequency of complications to the bladder and rectum 
 
Primary objective:  
 
The primary outcome is the absence of complications to the bladder, rectum or other pelvic structures detected 
in the first week after therapy. Each patient will be judged free of these adverse events or not. For those with an 
adverse event, the complication will be scored as to severity and outcome, as defined in the adverse events 
section of this protocol  
 
Secondary objectives:  
Improvement in the International Prostate Symptom Score (IPSS), a validated and well-accepted symptom and 
quality of life questionnaire. 
Improvement in the International Index of Erectile Function (IIEF-5), a validated questionnaire to assess 
erectile function. 
Improvement in Uroflowmetry (Qmax) post embolization 
Prostate volume compared to a pre and post embolization US 
Serum PSA pre and post procedure 
Post procedural pain as measured on a visual analogue scale (VAS). 
Procedure time and radiation parameters (fluoroscopy time, dose area product, cumulative dose). 
Prostate volume as determined by measurements of the gland using MRI. 
Extent of devascularization of prostate tissue as estimated from contrast-enhanced MRI. 
Study Plan 
Objectives of the investigation 
This is a Phase I-II study with the primary goal of determining the safety of prostatic artery embolization (PAE) 
for benign prostatic hyperplasia. Our primary outcome is the frequency of adverse events, particularly bladder 
and rectal complications, which may occur as a result of this procedure. Secondarily, the study will allow us to 
begin to determine its effectiveness in diminishing obstructive symptoms associated with BPH. 
Duration of investigation 
The investigation will enroll 30 patients, with a target enrollment period of less than 12 months. Each patient 
will be consented for follow-up up to 5 years, but each patient will reach the first important safety endpoint 1 
week after treatment and the first clinical efficacy assessment 3 months after treatment. 
 
Written Protocol 
Objectives 
To determine the safety and effectiveness of prostate artery embolization for the treatment of BPH. 
Description of study type 
This is a prospective observational non-comparative study of an initial cohort of 30 patients. 
Study Population 
The patients will be recruited from the urology practice at Georgetown University and from other urologists in 
the area and by patient self-referral. The study will be registered at clinicaltrials.gov and also will be announced 
on a study website, the content of which will be approved by the IRB at Georgetown University Medical Center 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
11 
and both of these sites may lead patients to self-refer for participation. 
Patient Inclusion Criteria 
1. Men presenting with benign prostatic hyperplasia with symptoms for at least 6 months that are refractory to 
medical management or in whom medications are contraindicated, not tolerated or refused. Additional 
criteria include: 
a. Moderate to severe obstructive urinary tract symptoms as defined as an International Prostate 
Symptom Score (IPSS) score of 12 or greater. 
b. Peak urinary flow (QMax) of less than 12 mL/s or acute urinary retention. 
c. Prostate volume of greater than 50 cc and less than 100 cc. 
d. Minimum age of 50 years, maximum age of 90 years  
Exclusion Criteria 
1. Presence of prostate cancer based on digital rectal exam (DRE), biopsy, Transrectal Ultrasound (TRUS), 
PSA > 10 ng/mL. 
2. Renal insufficiency (serum creatinine of greater than 1.8 mg/dL) 
3. Prior prostate surgery or intervention, including trans-urethral resection of the prostate, balloon dilation, 
stent implantation, laser prostatectomy, or hyperthermia 
4. Other bladder or urethral pathology requiring therapy, either in the past or currently, including neurogenic 
bladder, sphincteric abnormalities, bladder cancer, or other causes of bladder atonia 
5. Other causes of urinary obstruction, such as strictures of urethra or ureters not related to BPH 
6. History of cardiac arrhythmias, congestive heart failure, uncontrolled diabetes mellitus, significant 
respiratory disease, or known immunosuppression. 
7. Patients with coagulation disturbances 
8. Concomitant medications (use of alpha-blockers within two months, 5-alpha-reductase inhibitors within six 
months, anti-cholinergics within two months, and beta 
blockers/antihistamines/anticonvulsants/antispasmodics within one week of treatment unless there is 
documented evidence that the patient has been on the same drug with a stable voiding pattern) 
9. Active urinary tract infection 
10. Allergy to iodinated contrast agents 
11. Hypersensitivity to collagen or gelatin products 
12. Acute urinary retention untreated by urinary catheterization 
13. PVR > 250 mL as measured by ultrasound 
14. Cystolithiasis or hematuria within three months 
15. Previous rectal surgery, excluding hemorrhoidectomy, or history of rectal disease 
16. Prior pelvic irradiation or radical pelvic surgery 
17. Known major iliac arterial occlusive disease 
18. Contraindication to embolization, such as intolerance to vessel occlusion procedures, vascular 
anatomy/blood flow that precludes catheter placement or embolic agent injection, presence/likely onset of 
vasospasm, presence/likely onset of hemorrhage, severe atheromatous disease, feeding arteries smaller than 
distal branches, collateral vessel pathways endangering normal territories during embolization, and pelvic 
inflammatory disease. 
19. Men interested in future fertility 
Pre-procedure Patient Evaluation 
Patients may present in one of 3 ways: self-referral, referral from urologists or other community physicians or 
referral from the Urology Department. Prior to screening for the study, potential study participant will be 
provided information regarding the study. The informed consent form will be given to each potential participant 
and consent will be obtained prior to screening. 
 
Once patients agree to proceed and have signed a consent, they will be screened by the research coordinator for 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
12 
exclusion criteria. If they are not excluded, they will be evaluated by the co-investigator urologists and the 
following will be done.  
.  
a. IPSS will be administered 
b. Urine analysis, culture, sensitivity (if indicated) 
c. Blood chemistry (including blood count, BUN, serum creatinine) 
d. A baseline serum prostate specific antigen (PSA). 
e. A focused urologic physical examination, including a rectal exam and trans-rectal ultrasound to detect 
prostate volume.  
f. The patient will complete uroflowmetry, including voided volume (>125cc), total time of voiding, peak 
urine flow rate, average urine flow rate, and post-void residual volume. 
If either physical examination or PSA suggests possible prostate cancer, trans-rectal prostate biopsy will be 
performed. If prostate cancer is detected, the patient will be excluded. 
 
Provided participants are not excluded based on the above evaluation, at a separate visit, each will have: 
a. Anoscopy and cystoscopy in the urology clinic to ensure that these are normal, without mucosal 
abnormality. 
b. A baseline contrast-enhanced MRI of the prostate will be completed. 
c. The patient will also complete a 5 question sexual function questionnaire, the International Index of 
Erectile Function (IIEF). This questionnaire and the IPSS are described in detail in a later section. 
d. Each patient will have a consultation visit with one of the interventional radiologist co-investigators. 
The patient will have a focused physical examination, including vascular exam, and will have the 
procedure explained in detail. The procedure will be scheduled at that time.  
Procedure 
During the procedure conscious sedation with intravenous fentanyl and Versed will be provided. Ciprofloxacin 
400 mg administered intravenously prior to the procedure for antibiotic prophylaxis. The procedure will be 
performed in the Interventional Radiology suite by one or both of the study investigators.  A Foley catheter will 
be placed, with the balloon filled with contrast material to assist in prostate and bladder localization. Bilateral 
femoral arterial access will be obtained, unless evidence of vascular disease in the iliofemoral system precludes 
safe bilateral access. In that event, unilateral femoral access will be obtained.  Each patient will have a selective 
internal iliac arteriogram, and as necessary, an arteriogram of the anterior division of the internal iliac artery 
performed to identify the prostatic arterial supply. This typically arises from the inferior vesicle artery (also 
known as the prostatic artery), but may have supply from the superior vesicle, the internal pudental or obturator 
branches as well. 
The prostatic arteries will be selected using standard micro-catheter technique.  Embolization of the prostate 
will be performed with 300 to 500 um sized TAGM (Embosphere® Microspheres, Merit Medical, South 
Jordan, UT). The embolization endpoint will be absence of the normal blush of the prostate on post 
embolization angiography and stasis of flow in the prostate arteries. 
After the catheters are removed, hemostasis will be achieved with manual compression. 
Post-Procedure Care 
As the primary outcome is safety, each patient will be admitted for observation and short-term recovery 
overnight. Analgesics will be provided via IV PCA. During the observation period, each will be assessed on the 
severity of pain occurring during the first 24 hours after treatment using a visual analogue scale (VAS) 
administered by the nurse practitioner.  The assessment sheet will include a 10 cm linear VAS scale along with 
subjective questions regarding the patients’ degree of other symptoms, specifically rectal pain or bleeding, pain 
with urination or gross hematuria. After discharge, the patients will be called the next day to review symptom 
status and to screen for complications. 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
13 
Follow-up Care and Evaluation 
 
In the Table 2 below, the baseline and follow-up visits and the associated assessments at each visit are 
summarized. 
 
Table 2. Study assessment summary 
 
Prior to 
treatment 
Procedure 
1 week after 
treatment 
3 months 
6 months 
12 months and 
annually 
IPSS and IIEF 
Questionnaires 
Medical History 
Physical Exam 
CBC, Blood 
Chemistry, PSA 
UA, Urine C&S 
(if indicated) 
Urologic exam 
Urine Flowmetry 
Cystoscopy 
Anoscopy 
MRI (if not able, 
TRUS) 
2 hour 
procedure 
Sedation 
Bladder 
catheter 
(removed 
prior to 
discharge) 
Overnight stay 
Symptom 
assessment 
Adverse Event 
Assessment 
 
IPSS 
Questionnaire 
Symptom 
Questionnaire 
Urologic 
Exam 
CBC, Blood 
Chemistry, 
PSA 
UA, Urine 
C&S 
Cystoscopy 
Anoscopy* 
Urine 
Flowmetry 
Adverse Event 
Assessment 
IPSS and IIEF 
Questionnaires 
Urologic Exam 
CBC, Blood 
Chemistry, PSA 
UA, Urine C&S 
Urine 
Flowmetry 
Cystoscopy 
MRI (if not 
able, TRUS) 
Adverse Event 
Assessment 
 
IPSS and IIEF 
Questionnaires 
Urologic Exam 
CBC, Blood 
Chemistry, PSA 
UA, Urine C&S 
Urine 
Flowmetry 
Cystoscopy 
MRI (if not 
able, TRUS) 
Adverse Event 
Assessment 
 
IPSS and IIEF 
Questionnaires 
Urologic Exam 
CBC, Blood 
Chemistry, PSA 
(PSA only after 
12 months) 
UA, Urine C&S 
Urine 
Flowmetry 
Cystoscopy (12 
month only) 
MRI (if not 
able, TRUS) 
Adverse Event 
Assessment 
 
 
 
*repeat anoscopy at subsequent visits until resolves or stable for two consecutive examinations. 
Outcome Assessment Measures 
Laboratory Assessment 
The safety of the therapy will be monitored in part using laboratory analyses, including CBC, serum chemistry, 
urinalysis, urine culture and PSA. Of these, the urine testing is directed at assessing bladder function, while 
PSA trending will be an important outcome measure of prostate status. 
Urine Flowmetry 
Several tools have been developed to evaluate severity of LUTS and to track disease progression and response 
to therapy.  Urine flowmetry, which includes voided volume (>125cc), total time of voiding, peak urine flow 
rate (Qmax), average urine flow rate, and post void urinary volume, provides an objective measure of urinary 
function and will be measured in this study [29].   
Symptom and quality of life assessment 
While urinary symptoms are increased in larger prostates, prostate size does not always predict severity of 
symptoms. Many patients with enlarged prostates do not have symptoms and therefore no therapy other than 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
14 
watchful waiting is indicated. 
To provide a means of assessing symptom severity, the AUA symptom index and International Prostate 
Symptom Score (IPSS) have been developed and validated and have become important clinical tools directing 
management of LUTS attributed to BPH [30, 31].  These are self-administered questionnaires that assess the 
severity of symptoms including frequency, nocturia, urgency, incomplete emptying, intermittency, straining, 
and a weak stream. The questionnaires only differ in that the IPSS has an added quality of life question and for 
this reason that will be the questionnaire we use in this study. The IPSS asks patients to quantify the severity of 
these symptoms on a scale from 0-5 with a total overall score ranging from 0-35.  A symptom score of 0-7 is 
considered mild symptoms, 8-19 moderate, and 20-35 severe. The IPSS also includes a quality of life (QoL) 
question asking “If you were to spend the rest of your life with your urinary condition just the way it is now, 
how would you feel about that?” with a scale ranging from 0-6 (terrible to delighted). 
Erectile dysfunction is a key concern with prostate surgery and may be with prostate embolization as well. A 
standard questionnaire used for assessing erectile function is the International Index of Erectile Function (IIEF) 
[32] and a short 5 question version of this questionnaire (IIEF-5) has been developed and validated [33] and 
this is the version that will be used in this study. 
Visual inspection of the bladder and rectal mucosa 
Both cystoscopy and anoscopy will be used before and 1 week after therapy to assess the integrity of the 
mucosa and the impact that embolization has on the mucosa of these structures. As currently written, the 
cystoscopy will be repeated at 3, 6, and 12 months after therapy. Anoscopy would only be repeated if the 1 
week exam is abnormal and then it will be repeated until the exam is normal or stable on 2 consecutive 
examinations. 
Imaging Assessment 
Trans rectal ultrasound is the current standard imaging for the clinical assessment of the prostate gland [29]. 
Having said that, MRI can provide a more comprehensive assessment of the prostate size and tissue viability. 
Contrast-enhanced MRI provides a perfusion “map” of the prostate and allows the determination of the extent 
of infarction (or non-perfusion) of the prostate. The preliminary work in both Lisbon and Sao Paulo suggests 
that the greater the degree of de-vascularization of the prostate, the greater the volume reduction. This is likely 
to correlate with symptom improvement, although this requires confirmation. We believe that this study will 
provide preliminary data that can be used to help design studies to test that hypothesis. 
Adverse Events 
Each adverse event will be recorded as they occur. Each will be categorized as to type and severity using the 
Society of Interventional Radiology (SIR) definitions of adverse events based on outcome. That classification is 
as follows: 
Type 
Class 
Definition 
Minor 
A 
No therapy, no consequence 
 
B 
Nominal therapy, no consequence; includes overnight 
admission for observation only. 
Major 
C 
Require therapy, minor hospitalization (<48 hours). 
 
D 
Require major therapy, unplanned increase in level of 
care, prolonged hospitalization (>48 hours). 
 
E 
Permanent adverse sequelae. 
 
F 
Death. 
Analysis 
The primary outcome is the absence of complications to the bladder, rectum or other pelvic structures detected 
in the first week after therapy. Each patient will be judged free of these adverse events or not. For those with an 
adverse event, the complication will be scored using the SIR definitions. Descriptive statistics will be used to 
summarize these events, along with patient demographics and initial clinical status. 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
15 
Appropriate parametric and non-parametric tests will be used to assess change in laboratory measures, urine 
flowmetry parameters, and scores from the IPSS and IIEF. Changes in prostate volumes and the estimated 
volume of devascularized tissue will be calculated for each patient and outcomes from the different embolics 
will be compared. Appropriate paired parametric and non-parametric tests will be used to determine statistical 
significance. A p value of 0.05 will be considered statistically significant.  
 
Statistical Considerations (justification for sample size or “n”, power or degree of change): 
Descriptive statistics will be used to summarize these events, along with patient demographics and initial 
clinical status. 
Appropriate parametric and non-parametric tests will be used to assess change in Q Max flow, IPSS, IIEF and 
the SF-36. Changes in prostate volumes and the estimated volume of devascularized tissue will be calculated. 
Relative importance/value of the trial, considering “standard” therapy and competing trials: 
An alternative procedure to surgery with durable results would be beneficial to patients with LUTS who cannot 
tolerate medical therapy or cannot have surgery performed for other comorbidities. 
 
Feasibility of study including projections for accrual of subjects (Total and Georgetown University) and 
timeline for accrual: 
 
 
Anticipated Accrual for local site? 30 
 
                    
 
Overall Target Accrual? 30 
 
How Long Will Study Be Open to Accrual?_____12-24________ month(s) 
 
Duration of Study?____5 years after last recruited patient. 
 
 
 
 
6. 
Risks: Indicate what you consider to be the risks to subjects and indicate the precautions to be taken to 
minimize or eliminate these risks. Justify the need for a placebo control group if one is included in this study. 
Where appropriate, describe the data monitoring procedures that will be employed to ensure the safety of 
subjects. Use additional sheets as needed. 
 
This is a Phase I-II safety study focused on the local risks in the pelvis of this procedure. While there are other 
potential risks due to the iodinated contrast, arterial puncture and the passage of the catheters within the vessels, 
these risks are very low, well less than 5% and no greater than for any other arteriographic procedure. Other 
potential risks related to an embolization procedure include the risk of conscious sedation and radiation 
exposure. We anticipate this procedure taking on average about 30 minutes of fluoroscopy and approximately 
100 angiographic images. We will use ALARA principles to reduce X-ray exposure, including tight 
collimation, maximizing tube subject distance, varying angulation of the X-ray beam, slow pulsed fluoroscopy 
rates and slow filming rates for angiographic series. We will record all available exposure factors for 
subsequent analysis, as well as patient BMI. The radiation safety officer at Georgetown University Hospital has 
reviewed our approach and has approved it from a radiation safety perspective.  
We cannot accurately estimate the risk of bladder or rectal injury as detailed analysis of the currently reported 
patient experience has not been reported. We have visited both the group in Lisbon, who have now treated over 
250 patients and the Brazilian group has treated over 70 patients. There have been no serious rectal injuries 
reported. There has been one injury in the Lisbon group to the bladder that resulted in the need for bladder 
resection.  
Therefore, the current experience would suggest that the risk of complication is low, with the risk of a serious 
complication is extremely low (less than 1% chance) but that is based on clinical experience and not careful 
assessment of the rectum and bladder. This is the main focus of our study 
Based on the reported data to date and known potential complications of angiographic procedures, the 
following are potential risks of the procedure: 
Related to the embolization of the prostate: Minor or self-limited complications: burning in the urethra, urinary 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
16 
infection, hematuria, hematospermia, hemorrhage, vasospasm, rectorrhagia, pain in the pelvis, or allergic 
reaction to embolic material. 
More serious complications related to embolization of the prostate: bladder or bladder neck necrosis, possibly 
requiring surgical resection. Bladder ischemia causing severe pain, but resolving without complication. Other 
than the one case of surgical resection of the bladder in Lisbon, all reported complications have resolved with 
minimal or no therapy. 
Complications related to angiography: arterial injury, which in rare instances (<1%) can lead to need for 
surgical repair of the artery, arterial injury in the pelvis, puncture site hematoma and allergic reaction to the 
contrast media. 
Radiation injury to the skin of the buttocks- this complication is not yet reported but is possible with prolonged 
procedures. 
 
Risk Minimization 
As noted above, great care will be taken with the use of X-ray exposure to minimize dose. Similarly, each 
patient will be evaluated pre-procedure for sedation risk according to the standard of care and will be followed 
by both the interventional radiology and urology staff physicians. 
 
Each significant injury to a patient’s bladder or rectum will be reported immediately to the IRB staff. Those 
with lesser injuries will be recorded and followed to resolution. All minor and major complications will be 
summarized after each set of 10 patients and reported to the IRB. We currently plan to stop the study for re-
evaluation of its overall safety if more than 20% of patients assessed after the first 10 patients (and each 
subsequent group of 10 patients) suffers either a bladder or rectal injury requiring surgical intervention. 
 
We do not believe a data safety and monitoring committee is needed as our urology co-investigators will serve 
the role of safety monitors. They have a strong incentive to identify injuries, as they do not perform this 
procedure and it has the potential to compete with traditional therapies. While our urology colleagues are 
interested in providing alternatives to TURP for their patients, they have no interest in a therapy that is not safe. 
 
 
7. 
Does a Data Safety and Monitoring Board exist?   
 Yes  
 
 No 
[A Data Safety and Monitoring Board, an independent group of experts, will review the data from this 
research throughout the study. Patients will be told about new information from this or other studies that may 
affect their health, welfare, or willingness to stay in this study.] 
 
8. 
Does this study include a Placebo? 
 Yes  
 
 No 
     
 
9. 
Website Summary:  If this is an open clinical trial, recruitment material for clinical trials and information 
for sponsors about the type of research we do will be posted on the Clinical Trials website. Please create a 
brief summary, in Layman Terms (8th grade language) of 200 words or less for this protocol outlining the 
salient features that may be useful to public and health care professionals.  
http://clinicaltrials.georgetown.edu/index.html 
 
 
The Departments of Radiology and Urology at Georgetown University Hospital are collaborating on a research 
study to determine the safety and effectiveness of prostate embolization, a new treatment for men who have 
enlarged prostate glands and urinary obstruction. Men with urinary obstruction usually have frequent urge to 
urinate, a weak urine stream, difficulty starting to urinate and may need to urinate numerous times each night. 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
17 
Prostate enlargement (medically known as benign prostatic hyperplasia) is due to overgrowth of the prostate 
gland tissue and is very common in older men. This is not related to prostate cancer, although all patients 
treated in this study and for prostate enlargement in general are screened to be sure there is no evidence of 
prostate cancer. 
 
The new treatment, prostate artery embolization, is a minimally-invasive procedure done while a patient is 
sedated. After local anesthesia, the artery at the top of the leg is entered with a catheter (a thin long tube), which 
is then advanced into the arteries feeding the prostate gland. Small beads are injected into the arteries to block 
the blood supply to the prostate tissue, causing that tissue to shrivel and shrink. The procedure takes from 2 to 3 
hours and will require only an overnight observation stay in the hospital. The patient can return to normal 
activities within a day or two of treatment. 
 
There are no studies on prostate artery embolization that have been completed in the United States. The studies 
that have been completed in other countries to date suggest that this is effective in most men in causing the 
urinary symptoms to significantly improve or disappear. The data so far also suggests that this is safe, with few 
complications. 
 
This study will focus first on the safety of the procedure to be sure there are no injuries to other pelvic 
structures, such as the bladder or rectum, which are very near the prostate. The current experience in other 
countries suggests that these types of injuries are very rare, but we plan on a detailed analysis to accurately 
assess the risk. The study will also measure the severity of symptoms before and after the procedure and to 
evaluate whether the prostate shrinks and the extent of scarring of the prostate tissue. 
 
With any treatment, the long-term outcome is also a key question. There are no long-term studies of this 
procedure yet completed. We hope to follow patients treated for up to 5 years after treatment by questionnaire 
to determine if once gone, the symptoms ever return.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
18 
10. Data Safety and Monitoring Plan 
 
10.1 
Assignment of Risk Levels – Please select the risk level for your study and check the boxes that apply. 
 
10.1.A 
Research involving minimal risk only if one of the following applies: 
 
 
Anthropomorphic evaluations 
 
DEXA scans 
 
Electrocardiograms (EKGs) 
 
Exercise testing 
 
Intravenous glucose tolerance tests 
 
Intravenous catheter insertion 
 
Magnetic resonance imaging (MRI) scans 
 
Observational studies 
 
Oral glucose tolerance tests 
 
Pathology slide review 
 
Special/prescribed diets 
 
Venipuncture 
 
Other non-therapeutic tests or studies. Please list: 
 
 
 
 
Note: In the assignment of risk levels, a research survey may be considered more than minimal risk to subjects if 
dealing with very sensitive information. 
 
10.2 
Plans for Reporting of Adverse Events Including Subject’s Death.  
 
Adverse events from this protocol will need to be reported to the IRB, GCRC RSA (if the study is being 
conducted on the GCRC), and GCRC Nurse Manager (if the study is being conducted on the GCRC).  In the 
section below, please list other individuals and/or entities to whom adverse events will be reported. 
 
Individual/Entity 
 
Investigator 
 
National Institutes of Health and/or 
 
Food and Drug Administration (FDA) 
 
Other agency or sponsor 
Please specify:  
 
 
 
10.2.1 Who is the individual/entity primarily responsible for AE and to whom they are primarily reported. 
 
Name 
Position 
James B Spies MD 
Principal Investigator 
 
 
Plans for Monitoring the Progress of Trials and the Safety of Participants 
 
10.2.1 Safety tests. In the section below, please indicate the summary of safety tests, particularly those that 
screen out ineligible research subjects and those that monitor for toxicity and other adverse outcomes. 
Clinical evaluation will be used before to exclude those that have renal insufficiency, iliac artery occlusion, and 
prostate cancer. 
 
Office anoscopy and cystoscopy will be completed before the procedure and at regular intervals after to evaluate 
the bladder and rectal mucosa. This is the most sensitive test to detect ischemic injury.  

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
19 
 
All X-ray parameters will be recorded to estimate patient exposure. At the 1 week and 3 month office visits, each 
will have the skin of the buttock assessed, as this is the most likely site for an radiation injury and it should be 
manifest between 1 week and 3 months after exposure. 
 
10.2.2 Safety Contact Information. In the section below, please include a description of who will manage the 
patients and be responsible for assessing subjects’ responses including potential adverse events during 
their participation in the protocol. Please provide 24-hour contact information of the PI or other 
responsible member of the study team. 
 
Name 
Role on the 
Project 
Can be 
contacted 
24X7?  
Contact Information 
James B. Spies MD 
Principal 
Investigator 
Yes 
Phone: 202-444-3450 
Pager: 202-405-3733 
E-mail: spiesj@gunet.georgetown.edu 
Alex Kim MD 
Co-Investigator 
Yes 
Phone: 202-444-3450 
Pager: 202-405 
E-mail: 
Alexander.Y.Kim@gunet.georgetown.edu 
John Lynch MD 
Co-investigator 
Yes 
Phone: 202-444-4688 
Pager: 202-405-2483 
E-mail: lynchj@gunet.georgetown.edu 
Keith Kowalczyk MD 
Co-investigator 
Yes 
Phone: 202-444-4922 
Pager: 202-4055017 
E-mail: 
Keith.Kowalczyk@gunet.georgetown.edu 
 
 
 
Phone:  
Pager:  
E-mail:  
 
 
 
 
10.4.3 Description of Individuals/Entities in Charge of Dispensing Drugs. In the section below, please include the 
description of individuals and/or entities in charge of dispensing the drugs. 
 
Name 
Role on the Project 
Contact Information 
Michelle Jones, NP 
Nurse Practitioner/ clinical 
coordinator 
 
Phone: 202-444-5479 
Pager: 202-405-2520 
E-mail:  
Merry Preziosi NP 
Nurse Practitioner/clinical 
coordinator 
Phone: 202-444-7014 
Pager: 202-405-5004 
E-mail:  
 
 
 
 
 
 
10.4.4 Safety Monitoring Methods and Intervals 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
20 
 
In the section below, please check all that apply. 
 
Data to be Evaluated 
Interval/Frequency of Evaluation* 
 Age specific intervention(s) 
1 week after treatment, 3 months, 6 months, 12 
months and annually for 5 years. 
 Clinical test(s) 
 Subject interview and/or contact 
X  Subject’s physical exam 
 Subject’s symptoms or performance status 
 Subject’s vital signs 
X Other study parameters. Please list: 
 
 
 
 
 
 
10.4.5 Decision Making Criteria and Stopping Rules 
 
In the section below, please describe data safety monitoring criteria for decision-making regarding continuation, 
modification, or termination of the clinical study. 
The study will be stopped if any two patients in any 10 patients suffer either a bladder or rectal injury requiring 
surgical intervention. Thus if in the first 10 patients, two patients have this type of injury, the study will be 
stopped. Similarly, if two patients in any set of 10 patients has this type of injury, the study will be stopped. After 
each 10 patients, a report on complications will be submitted to the IRB. 
 
 
10.4.6 Monitoring of the Study 
 
In the section below, indicate who will monitor the study and to whom the study will report. Describe the 
frequency of the monitoring. If a DSMB is required, describe the composition of the board, its role, and the 
frequency of meetings and methods of communications. 
The urology staff will serve as safety monitors. Each significant injury  (requiring surgical intervention) to a 
patient’s bladder or rectum will be reported immediately to the IRB staff. Lesser injuries will be recorded and 
followed to resolution. All minor and major complications will be summarized after each set of 10 patients and 
reported to the IRB.  
 
 
10.4.7 Subject Withdrawals/Dropouts 
 
In the section below, please describe how subject withdrawals/dropouts prior to study completion will be 
reported. Include examples of reasons that may prompt subject withdrawals/dropout. 
Other than patient unwillingness to complete follow-up, we do not anticipate other reasons for withdrawals. 
Unless a withdrawal is associated with a significant injury, withdrawals will be reported after each 10 patients 
with the report regarding other complications. 
 
 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
21 
Section Four: Selection of Subjects and the Informed Consent Process 
 
11. Indicate whether this project involves any of the following subject populations? 
 Children (Children are defined by local law as anyone under age 18.) 
 Prisoners 
 Pregnant women 
 Cognitively impaired or mentally disabled subjects 
 Economically or educationally disadvantaged subjects 
 
If you indicated any of the above, in the space below please describe what additional safeguards will be in place 
to protect these populations from coercion or undue influence to participate. (Use additional sheets as needed.) 
 
 
Not applicable 
 
 
 
 
 
 
 
 
 
12. Recruitment: Describe how subjects will be recruited and how informed consent will be sought from 
subjects or from the subjects’ legally authorized representative. If children are subjects, discuss whether their 
assent will be sought and how the permission of their parents will be obtained. Use additional sheets as 
needed. 
 
 
Patients will be recruited via clinicaltrials.gov and also through a web page placed on the Radiology 
Department hospital website. The same information will be listed on both sites. 
 
Informed consent and the HIPAA release will be obtained at the time of initial clinical assessment. The patients 
will all have been given the consent and patient summary prior to that visit so that they will be informed of the 
study procedures, the exams they will have to undergo and the anticipated risks. 
 
 
 
 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
22 
13. Does the review of this protocol include evaluation of patient population to ensure women and 
minorities are included, if appropriate? 
  
Yes. This study is open to both men and women, and to all racial/ethnic groups. Since there are 
no prior reasons to expect different effects of therapy in male and female patients, and in 
different racial/ethnic groups, this study will not have separate accrual targets for these groups. 
Subgroup analyses will be conducted to determine gender and race/ethnicity treatment effects and 
will document any interactions between treatment and these factors.  
 
 No 
 
The study is limited to male patients with benign prostatic hypertrophy and obstructive urinary symptoms.  The 
study is open to all racial and ethnic groups. Only patients able to read and write English will be included to 
facilitate completion of questionnaires. 
 
 
 
 
 
 
 
14. Other Exclusions: Please check the corresponding box if any of the following populations is excluded. 
  HIV  
  Pediatric 
  Other ____________________________________________________________________________ 
 
Explain the rationale for excluding any sub-populations populations in the space below. 
 
This is a male only study. Patients must be able to read and write English to complete the questionnaires. 
 
 
 
 
 
 
 
 
 
15. Will subjects receive any compensation for participation in cash or in kind? 
 Yes  
 
 No 
 
 
If subjects receive any compensation, please describe amount or kind of compensation in the space below. 
 
Not applicable 
 
 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
23 
Section Five: Privacy and Confidentiality of Data and Records 
 
16. Will identifiable, private, or sensitive information be obtained about the subjects or other living individuals?  
Whether or not such information is obtained from a covered entity (GUH, WHC, etc), describe the provisions 
to protect the privacy of subjects and to maintain the confidentiality of data. If the information does come 
from a covered entity, please attach a copy of the completed appropriate HIPAA General Authorization Form 
or Request for Waiver.  Use additional sheets as needed. HIPAA compliant forms for MedStar may be found 
at the following website:  
 
 
http://www.medstarresearch.org/body.cfm?id=87 
 
 
 
 
Each patient will be assigned a 4 digit sequential number for all patients screened for the study. Contact data 
will be collected but kept separate from all clinical data. A screening form will be completed by each patient, 
but the personal identifiers will not be included on that form. All questionnaires and all clinical data forms will 
be marked with the patient identification number and initials, but no other identifiers 
 
All data forms will be kept in a locked file cabinet in a secured office. Any data entered in a computer database 
will be marked by the patient identification number only.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Georgetown University Institutional Review Board 
IRB Number: ________________ 
Form AB-1 (2007/07/05) 
24 
 
I certify that the information furnished concerning the procedures to be taken for the protection of human 
subjects is correct. I will seek and obtain prior approval for any modification in the protocol or informed 
consent document and will report promptly any unexpected or otherwise significant adverse effects 
encountered in the course of this study. 
 
 
I certify that all individuals named as consultants or co-investigators have agreed to participate in this 
study. 
 
 
I assure that the protected health information identified on the “Medical Records Release and General 
Authorization to Use and Disclose Health Information for Research” and the persons and entities that may 
use, give and receive protected health information is accurate and reflective of the known use and 
disclosure for this human clinical study. 
 
 
James B. Spies MD 
____ ________________________________ 
Printed/Typed Name of Investigator 
 
____________________________________ 
Signature of Investigator 
202-444-3450 
_____________________________________ 
Telephone number 
 
_____________________________________ 
Date 
 
Cirrelda Cooper MD  
____________________________________ 
Printed/Typed Name 
 
____________________________________ 
Signature of Department Chair 
Department Chair: 
 Approved 
 
 
 
 Disapproved  
202-444-3450 
____________________________________ 
Telephone Number 
________________________________ 
Date 
 
 
 
If more than one department or administrative unit is participating in the research and/or if the facilities or support 
of another unit, e.g., nursing, pharmacy, or radiation therapy, are needed, then the chair or administrative official 
of each unit must also sign this application. 
 
____________________________________ 
Authorized Signature 
Chairman, Department of Urology 
____________________________________ 
Title and Department 
 
 
 Approved 
 
 Disapproved 
 
__________________________________ 
Date 
 
____________________________________ 
Authorized Signature and Title 
 
____________________________________ 
Title and Department 
 
 
 Approved 
 
 Disapproved 
 
__________________________________ 
Date 
 
____________________________________ 
Authorized Signature and Title 
 
____________________________________ 
Title and Department 
 
 
 Approved 
 
 Disapproved 
 
__________________________________ 
Date 

Section Six: Attachments  
Please attach the following items in order for the IRB to review your research. 
 
24 Copies of the Following for Full Board review, only 1 copy for Expedited Review: 
 IRB Application form (Form AB-1) 
 Informed Consent Document  
 Any recruitment notices or advertisements 
 Any research survey instruments, psychological tests, interview forms, or scripts to be used 
 HIPAA In-house Authorization or Request for Waiver* 
 Any communications from the FDA regarding IND, IDE, or humanitarian use applications related to this 
submission.  
 
One Copy of the following, when applicable 
 Request for Expedited Review (Form AB-3) 
 Request for Exemption (Form AB-4) 
 
5 Copies of the Following for Full Board review, only 1 copy for Expedited Review: 
 Investigator’s Brochure from the sponsor, if applicable** 
 Research protocol and sample consent document from the sponsor or Cooperative Group, if applicable 
 For all DOD sponsored studies – documentation of scientific review and approval 
 
2 Copies of the following, if applicable 
 Grant application 
 
One Copy of the following forms for Principal Investigator and ALL Co-Investigators 
 Certificate of Completion for HIPAA training and HIPAA forms.* 
 Conflict of Interest or Financial Disclosure Form  
 Certificate of Completion of Education in the Protection of Human Research Subjects*** 
 Investigator’s qualifications (CV, biosketch, or Form 1572, if available) 
 If this project involves an FDA regulated drug or device, FDA form 3455 
 
* 
HIPAA Training 
All persons listed on the IRB application, Co-Investigators Page, Investigator’s Agreement or 1572 of any 
research protocol will need to have completed the HIPAA training module for Researchers in order to 
secure IRB approval. Additionally, Investigators will need to assure that all key personnel involved in the 
research, especially personnel with data access and patient contact, have completed the HIPAA training 
module for Researchers. For more information and to download forms, please refer to the following 
MedStar website: 
 
 
 http://www.medstarresearch.org/departments/ora/HIPAA/hipaaintro.htm 
** 
Investigator’s Brochure (where applicable) 
The Investigator’s Brochure must contain the following information. If it does not contain the 
information, then please attach a separate sheet of paper to address the item. 
 
Name of drug under study. 
 
Source of the drug. 
 
Experience with the drug in humans, including doses tested, toxicity observed, minimal toxic 
dose, pharmacokinetic data (absorption, elimination, metabolism, etc.). 
 
Description of toxicity in humans. 
 
Procedures for minimizing adverse reactions and dealing with those that might occur. 
*** 
Information on Human Subjects Protection in Research Training: 
  
 
http://www.georgetown.edu/OSP/HumanSubjs.htm