Gastric artery Embolization Trial for the LEssening of Appetite

Presented by:
Mubin I. Syed, MD, FACR, FSIR
President, Dayton Interventional Radiology
Clinical Associate Professor of the Radiological Sciences
Wright State University School of Medicine
*Financial Disclosure: Partial funding for above study provided by SIR Foundation Pilot Research
Grant. No other relevant financial relationships.
Mubin Syed, M.D.
•No relevant financial relationship reported
Obesity Epidemic
 2008: 1.5 billion overweight; 500 million obese (1 in
every 8)
 Major risk factor for diabetes, heart attacks, stroke,
cancer, osteoarthritis
- Increases risk of diabetes 18-fold
 Fifth leading risk for death globally
 Ex. 25 year old morbidly obese loses 12 years (on
average)
Obesity Epidemic Cont.
 The number of obese people in the world rose from 105
million in 1975 to 641 million in 2014, with obesity rates
rising from 3 percent to 11 percent among men and
from 6 percent to 15 percent among women, the study
found.
 The researchers added that about one-fifth of adults
could be obese by 2025.
 Over the same time, the proportion of underweight
people fell from 14 percent to 9 percent of men and
from 15 percent to 10 percent of women, according to
the study
HEALTH: http://news.health.com/2016/03/31/more-of-the-worlds-people-are-now-obese-than-underweight/. Accessed April 14, 2016.
Diabetes Epidemic
 1 in 10 American adults has diabetes (if the trends
continue, the number of people with diabetes is
expected to double or even triple by 2050.
 Every 5 minutes, 2 people die from diabetes and 14 are
newly diagnosed.
 90% - 95% of all diabetes cases are type 2
 86 million adults in the U.S. who had prediabetes in
2012
http://www.healthline.com/health/diabetes/facts-statistics-infographic#3
Background
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Arepally, et al. (2008) first described the technique of gastric artery embolization to reduce weight
gain. In a controlled study, he used sodium morrhuate within a porcine model with resultant lower
ghrelin levels and significantly blunted weight gain (in otherwise rapidly growing young swine).
Paxton, et al. (SIR abstract in 2012, later published in 2013 and 2014) described the technique of 40
micron microsphere particle embolization in a similar porcine model that also resulted in lowered
ghrelin levels and reduced weight gain. Also noted there was no duodenal upregulation for ghrelin.,
Bawudun et al. (2012) described a technique of left gastric embolization using mixture of bleomycin
and lipiodol versus polyvinyl alcohol 500-700 micron particles to create weight loss in a canine model
without gastric ulceration. In addition, he demonstrated significant reduction in subcutaneous fat
and plasma ghrelin.
Kipshidze, et al. (2013) performed the first in man study reported at the annual meeting of the
American College of Cardiology that showed an average of 45lbs of weight loss in 6 months and
reduced ghrelin levels in 5 patients with no complications (with endoscopic follow-up) in this small
series using BeadBlock 300-500 micron particles. According to personal correspondence with the
author of this study the weight loss is sustained for at least 1 year with no complications in these 5
patients. He also noted that an additional 2 patients have been treated without complications.
Arepally A, Barnett BP, Patel TH, Howland V, Boston RC, Kraitchman DL,Malayeri AA. Catheter-directed gastric artery chemical embolization suppresses systemic ghrelin levels in porcine model. Radiology.
2008 Oct;249(1):127-33. doi: 10.1148/radiol.2491071232. Erratum in: Radiology. 2008 Dec;249(3):1083.
Paxton BE, Kim CY, Alley CL, Crow JH, Balmadrid B, Keith CG, Kankotia RJ, Stinnett S, Arepally A. Bariatric embolization for suppression of the hunger hormone ghrelin in a porcine model. Radiology. 2013
Feb;266(2):471-9
Paxton BE, Alley CL, Crow JH, Burchette J, Weiss CR, Kraitchman DL, ArepallyA, Kim CY. Histopathologic and immunohistochemical sequelae of bariatricembolization in a porcine model. J Vasc Interv Radiol.
2014 Mar;25(3):455-61.doi: 10.1016/j.jvir.2013.09.016. Epub 2014 Jan 21.
Bawudun D, Xing Y, Liu WY, Huang YJ, Ren WX, Ma M, Xu XD, Teng GJ. Ghrelin suppression and fat loss after left gastric artery embolization in canine model. Cardiovasc Intervent Radiol. 2012
Dec;35(6):1460-6.
Kipshidze, N, Archvadze, A, Kantaria, M, Konstantine, M, First -In-Man study of left gastric artery embolization for weight loss. American College of Cardiology Annual Meeting, 2013, Mar 10, Presentation
Number: 1209M-159.
Background
 Current active trials
 GET LEAN: Gastric Artery Embolization Trial for
the Lessening of Appetite Nonsurgically

Dayton Interventional Radiology and Ohio State
University
(2 sites)
 BEAT Obesity: Bariatric Embolization of Arteries
for the Treatment of Obesity

Johns Hopkins University Medical Center
Purpose
 The purpose of this pilot study is to achieve the collection of
safety and efficacy data in patients undergoing left gastric
artery embolization for morbid obesity in the Western
Hemisphere.
Materials and Methods
 This is an FDA-IDE pilot study. Five(5) patients have been approved to
undergo the left gastric artery embolization procedure for the purpose
of weight loss using Beadblock 300-500 micron particles. All patients
are required to receive an EGD follow up pre and post procedure.
Ghrelin, Leptin and CCK levels will also be measured at baseline and
post procedure per follow up protocol.
Protocol
 Pre Procedure:
 Gastric emptying study, CTA, Ghrelin, Leptin, CCK, CBC, Creatinine, EGD,
Bariatric consult, Dietician consult, Proton pump inhibitor seven(7) days
prior, SF-36v2, Endocrinology consult and HgbA1C (if diabetic)
 Post Procedure:
 Follow up at 3 days, 1 week, 1 month, 3 months, 6 months, and 1 year from
the date of procedure
 EGD at 3 days (again at 30 days if any abnormalities)
 Gastric emptying study at 3 months
Inclusion Criteria
 Morbid obesity with a BMI ≥ 40
 Age ≥ 22years
 Ability to lay supine on an angiographic table
 <400lbs due to table weight limits
 Appropriate anesthesia risk as determined by certified anesthesia
provider evaluation pre procedure
 Subjects who have failed previous attempts at weight loss through diet,
exercise, and behavior modification (as it is recommended that
conservative options, such as supervised low-calorie diets combined
with behavior therapy and exercise, should be attempted prior to
enrolling in this study).
Exclusion Criteria
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Major Surgery within the past eight weeks
Previous gastric, pancreatic, hepatic, and/or splenic surgery
Previous radiation therapy to L or R upper quadrant
Previous gastric, hepatic, and/or splenic embolization
Any history of portal venous hypertension
Serum creatinine > 1.8 mg/dL
History of kidney problems
Pregnant or intend to become pregnant within 1 year
History of Severe bleeding (platelet count less than 40,000)
Enrolled in another study
History of allergic reaction to iodinated contrast
Abnormal baseline studies (gastric emptying, CTA, EGD, etc)
Active substance abuse or alcoholism
Hiatal Hernia
Known aortic disease, such as dissection or aneurysm
…
Exclusion Criteria Cont.
 Defined noncompliance with previous medical care
 Subjects with mesenteric atherosclerotic disease or abdominal
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angina should be excluded due to safety concerns.
Comorbidity such as cancer, peripheral arterial disease or other
cardiovascular disease
Patients with any abnormality on their baseline EGD
Patients taking anti-coagulants
Patients taking or requiring chronic use of NSAID or steroid
medications
Patients with any history of peptic ulcer disease
Certain psychiatric disorders such as schizophrenia, borderline
personality disorder, and uncontrolled depression, and
mental/cognitive impairment that limits the individual’s ability to
understand the proposed therapy
PLEASE note that GET LEAN does not exclude diabetics and does
not exclude patients with H. Pylori (50% of the population) and
currently does not exclude anatomic variants
Technique
 Femoral or radial artery access
 Pigtail catheter for flush aortogram
 Reverse curve catheter to access celiac artery followed
by the left gastric artery
 Coaxial microcatheter for selective left gastric
arteriogram past esophageal branch
 Particle embolization using BeadBlock 300-500
micron to stasis (at least 5 cardiac pulsations)
 Closure device
Celiac Angiogram
Main Branch of Left Gastric Artery
Accessory Left Gastric Artery
Branch
PRE
POST
Results
(BMI/WEIGHT)
Subject
Age
Sex
Last Visit
Pre - Weight
CH1190
54
F
12 Months
199lbs
THO6761
35
F
6 Months
270lbs
CRA1984
30
M
6 Months
272lbs
ADK1970*
45
F
3 Months
296lbs
Subject
Last Visit
Weight
Weight Lost Pre-BMI
CH1190
151lbs
48lbs
40.2
30.5
THO6761
264lbs
6lbs
44.9
43.9
CRA1984
263lbs
9lbs
40.2
38.8
ADK1970*
270lbs
28lbs
44.3
40.2
*Diabetic Patient
Current BMI
Results (WEIGHT in lbs)
Subject
baseli
ne
weight
1 month
3 months
6 months
12
months
CH1190
199lbs
184lbs (-15)
169lbs (-30)
161lbs (-38)
151lbs(-48)
THO6761
270lbs
258lbs (-12)
270lbs (0)
264lbs (-6)
pending
CRA1984
272lbs
266lbs (-6) 260.5lbs (-11.5)
263lbs (-9)
pending
ADK1970*
296lbs
275lbs (-21)
270lbs (-26)
268lbs (-28)
pending
-13.50lbs
-16.88lbs
-20.25lbs
-48.00lbs
Average
weight
change
*Diabetic Patient
Results (WEIGHT in lbs)
350
300
250
200
150
CH1190
100
THO6761
50
0
CRA1984
ADK 1970
Results (WEIGHT in %)
Subject
baseli
ne
weight
1 month
3 months
6 months
12
months
CH1190
199lbs
-7.53%
-15.08%
-19.10%
-24.12%
THO6761
270lbs
-4.44%
0.00%
-2.22%
pending
CRA1984
272lbs
-2.21%
-4.23%
-3.31%
pending
ADK1970*
296lbs
-7.09%
-8.78%
-9.46%
pending
-5.32%
-7.02%
-8.52%
-24.12%
Average
weight
change %
*Diabetic Patient
Results (EWL in %)
EWL=(BL-post)/BL-IBW)*100 EWL=Excess Weight Loss)
Devine formula for IBW (1974)
Subject
baseli
ne
weight
1 month
3 months
6 months
12
months
CH1190
199lbs
-15.19%
-30.40%
-38.50%
-48.64%
THO6761
270lbs
-8.31%
0.00%
-4.15%
pending
CRA1984
272lbs
-5.17%
-9.91%
-7.75%
pending
ADK1970*
296lbs
-13.76%
-17.04%
-18.35%
pending
-10.61%
-14.34%
-17.19%
-48.64%
Average
EWL
change %
*Diabetic Patient
Human Clinical Results- GET LEAN
• Weight loss at 1 mos
13.5 ± 6.2lbs
 5.3 ± 2.5%
 10.6 ± 4.7% EWL
 Weight loss at 3 mos
 16.8 ± 13.7lbs
 7.0 ± 6.5%
 14.3 ± 12.8% EWL
 Weight loss at 6 mos
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20.3 ± 15.3lbs
8.5 ± 7.7%
17.2 ± 15.4% EWL
EWL=(BL-post)/BL-IBW)*100
Devine formula for IBW (1974)
EWL (Excess Weight Loss)
Preliminary Results of
Clinical Studies
Kipshidze
University
Hospital
Number
Follow-up
Total Weight
Loss Mean
Minor Adverse
Events
Major Adverse
Events
CV Center,
Frankfurt,
Germany
Ohio
Radiology,
Dayton, OH
John Hopkins
university
St. Ekaterina
Hospital, Odessa,
Ukraine
Total
5
1
4
5
1
16
24 mos
20 mos
6 mos
6 mos
2 mos
2-24mos
16%
12%
8.5%
8%
9%
0
0
3
2
1
6( 37.5%)
0
0
0
0
0
0
Reprinted with permission
from Nicholas Kipshidze, MD
SF36-V2 Pre/6mos/1yr
CH1190 Baseline
PF
RP
BP
GH
VT
SF
36.0
47.1
41.8
43.4 45.8 40.5
RE
MH
PCS
MCS
44.2
35.9
43.0
41.6
CH1190 6 month
PF
RP
BP
GH
VT
SF
RE
MH
PCS
MCS
46.5 56.9
55.4
47.2
42.7
45.9
48.1
41.6
54.0
41.8
CH1190 1yr
PF
RP
BP
GH
VT
SF
RE
MH
PCS
MCS
42.3
47.1
37.2 50.6 45.8
35
44.2 30.3
47.2
36.3
SF36-V2 – CH1190
100
80
60
40
20
0
PF
RP
BP
GH
PRE SF36V2
VT
SF
6 Mos SF36V2
RE
MH
PCS
1yr SF36V2
MCS
SF36-V2 Pre/Post
THO6761 Baseline
PF
RP
BP
GH
VT
SF
RE
MH
PCS
MCS
38.1
44.6 33.0
38.6
36.5
35.0
36.4
47.2
37.8
40.8
RE
MH
PCS
MCS
45.9 52.0
38.7
41.0
47.1
THO6761 6 month
PF
RP
BP
GH
VT
36.0
37.3
53.7
43.4
427
SF
SF36V2 – THO6761
100
80
60
40
20
0
PF
RP
BP
GH
VT
Baseline SF36V2
SF
RE
MH
6 month SF36V2
PCS
MCS
SF36-V2 Pre/Post
CRA1984 Baseline
PF
RP
BP
GH
VT
SF
RE
MH
PCS
MCS
29.7
32.4
41.8
41.0
45.8 29.6 40.3
33.1
36.0
38.9
RE
MH
PCS
MCS
56.8 52.0
61.3
53.2
58.2
CRA1984 6 month
PF
RP
57.0 54.4
BP
GH
VT
55.4 48.2
61.5
SF
SF36V2 – CRA1984
100
80
60
40
20
0
PF
RP
BP
GH
VT
Baseline SF36V2
SF
RE
MH
6 month SF36V2
PCS
MCS
SV-36 v2 Physical Component
60
50
40
Baseline
6 month
30
20
10
0
CH1190 THO6761 CRA1984 ADK1970
SF-36v2 Mental Component
60
50
40
Baseline
6 months
30
20
10
0
CH1190 ThO6761 CRA1984 ADK1970
Results (Ghrelin Levels)
1150
1100
1050
1000
950
900
850
Ghrelin
800
750
700
650
600
550
500
450
400
350
300
Pre
1 Week
1 Month
3 Month
6 Month
Follow Up
CH1190
THO6761
CRA1984
ADK1970*
1 Year
Ghrelin Chart
CH1190
THO6761
CRA1984
ADK1970*
Pre
691
543
391
822
1 Week
803
1,046
480
1096
1 Month
822
563
457
813
3 Month
1084
895
331
751
6 Month
961
598
354
668
6 mos %
39.1%
10.1%
-9.5%
-18.7%
939
538
1 Year
Results (Leptin Levels)
50
45
40
35
Leptin
30
25
20
15
10
5
0
Pre
1 Week
1 Month
3 Month
6 Month
Follow Up
CH1190
THO6761
CRA1984
ADK1970*
1 Year
Leptin Chart
CH1190
THO6761
CRA1984
ADK1970*
Pre
22.7
26.7
37.2
17.3
1 Week
12.3
18.6
19.5
15.9
1 Month
7.8
21.7
26.8
10.5
3 Month
7.7
34.7
16.2
13.6
6 Month
7.0
46.8
14.7
10.0
% change
-69.16%
75.28%
-60.48%
-42.20%
All patients who lost weight dropped Leptin levels
1 Year
4.0
Results (CCK Levels)
150
140
130
120
110
100
CCK
90
80
70
60
50
40
30
20
10
0
Pre
1 Week
1 Month
3 Month
6 Month
Follow Up
CH1190
THO6761
CRA1984
ADK1970*
1 Year
CCK Chart
CH1190
THO6761
CRA1984
ADK1970*
Pre
80
10
22
66
1 Week
36
107
38
99
1 Month
68
21
47
26
3 Month
88
97
31
38
6 Month
76
20
15
21
% change
-5.00%
100.00%
-31.82%
-68.18%
1 Year
47
Normal Hgb A1C-4.5 to 6.0
Prediabetic Hgb A1C- 5.7 to 6.4
Diabetic HgbA1C- >6.5
HgbA1C level in Diabetic patient
ADK1970
7.6
7.4
7.2
7
6.8
6.6
6.4
6.2
6
5.8
5.6
ADK1970
Baseline
1 month
3 months
6 months
12 months
Results – Minor Adverse Events
1) Anticipated adverse effect: Subjects #2, #3, and #4 all developed
superficial non-bleeding (cardia and body) gastric ulcerations at day 3
upper endoscopy. All of these superficial gastric ulcerations were
completely resolved on 30 day upper endoscopy. All patients with ulcers
were placed on Sucralfate 1gm bid for 30 days post procedure in addition
to the Proton pump inhibitor (PPI) therapy required by the protocol.
2) Anticipated adverse effect: Subjects #2, #3, and #4 all developed mild
nausea, occasional vomiting, and mild epigastric discomfort immediately
following the procedure that resolved within 24 hours for subjects #2 and
#4, and resolved within 3 to 4 days for subject #3. No patients required
hospital admission. All patients were able to maintain oral intake of food
and fluids.
3) There were no unanticipated adverse effects(no overnight hospital stays)
Follow Up
Patient 1 – The patient has lost a total of 38 lbs at 6 months (50
lbs at 9 months. She continues to report feeling a significant
decrease (50%) in her appetite since the procedure was
performed.
Patient 2 - The subject initially lost 12 lbs at 1 month, then
developed depression that was treated with an antidepressant,
Brentellix (vortioxetine) 20mg qd by her primary care physician
at 3 weeks and regained weight to baseline at 3 months. She
apparently had a prior history of depression (requiring
treatment with antidepressants) confirmed by her primary care
physician that she denied to us during the screening process.
She has since lost 6 lbs from baseline at 6 months.
Follow Up Cont’d
 Patient 3 - The subject has lost 11.5 lbs at 3 months. He then regained 2.5
lbs by 6 months for a total weight loss of 9 lbs from baseline. He was
found to have a markedly low free testosterone level 5.4 pg/ml (normal
9-24) by his primary care approximately 5 months following his
procedure. Patient was then placed on a topical testosterone medication
(Axiron 2% solution one 30mg pump to axilla each day) by his primary
care physician. Patient was also noted to have a prior history of
depression that he denied to us during screening. He was found later to
be on the antidepressants Celexa 20mg qd and Trazadone 50mg qhs for
11 months prior to the procedure that he did not report to us initially.
 Patient 4 - The subject has lost 28 lbs at 6 month follow up. She was the
first diabetic patient that was included in the study. She is followed by
an endocrinologist per protocol. Her HgbA1C has dropped from
7.4%baseline to 6.3% at 6 months.
1 year result 1st patient
GET LEAN STUDY
48 lbs lost or
49% EBW
equivalent to
surgical
outcome at
one year
Diabetic Patient
 First experience performing gastric artery
embolization for weight loss in a diabetic patient
 HgbA1C dropped from 7.4% to 6.3% in 3 month
 Blood sugar control improved.
Radial Artery Access
 First to utilize this approach for left gastric artery
embolization for weight loss
 No complications
All 4 patients were performed in the GET LEAN study at a free
standing center
Limitations of the Pilot Study
 Small Pilot study to initially assess safety
 Surgical placebo effect not excluded
Lessons learned from Pilot Study
 May not be effective in patients with depression
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(depressed patients tend to hide this history)
Consider psychological evaluation of all patient
In male patients, it may be worth adding testosterone
level prior to procedure
Patient motivation is important
Assess patient pain and disability index
This procedure is promising for appetite suppression,
however obesity is multifactorial in humans and many
people eat for reasons other than hunger
Lessons Learned
 Superficial ulcerations at 3 days on EGD tend to heal
with appropriate therapy by 30 days
 Symptoms can by managed in the outpatient setting.
 Procedure is feasible via a radial artery access
 Procedure is feasible in a diabetic patient

Conclusion
This is one of the first experiences in the United States of performing
left gastric artery embolization for the purpose of treating morbid
obesity. Early results are promising and show no major adverse events
thus far. The radial artery has also proven to be a feasible approach to
performing this procedure with implications for a safer access site. The
procedure also seems feasible in diabetic patients.
Conclusion Cont.
 Bariatric embolization, or gastric (stomach) artery
embolization promising treatment for obesity
 Can be done outpatient
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Potential for major weight loss equal to surgery
Diabetic patients may be candidates
Wrist artery access
Still too early for RCT
Need to improve effectiveness without increasing risk
(lower BMI, and smaller particles)
 Procedure is safe is short and intermediate term
 Appears to be effective in the short and intermediate term.
Future Directions
 Continuation of the FDA trial with additional patients
 Including further experience with radial artery access
and diabetic patients
 Inclusion of anatomic variants
 Possible use of alternative embolic agents (smaller
size)
 Randomized control trial
Disclaimer
 Procedure still experimental
 Still in infancy and being done only context of clinical
trials at this stage
Co-Authors: GET LEAN
 Kamal Morar, M.D. – Dayton Interventional Radiology
 Azim Shaikh, M.D. – Dayton Interventional Radiology
 Paul Craig, M.D. – University Of Minnesota Medical Center
 Talal Akhter, M.D. – Temple University Hospital
 Omar Khan, M.D. – University of Michigan Health System
 Sumeet Patel – Dayton Interventional Radiology
 Hooman Khabiri, M.D. – Ohio State University Wexner Medical Center