Gastric Artery Embolization Trial for Lessening Appetite Nonsurgically (GETLEAN)

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 United States. As secondary goal, the pilot study seeks to obtain quality of life data. This pilot study is not designed to achieve new indications for this device.

Beadblock will be used intraarterially to occlude in this case the left gastric artery and its branches. The left gastric artery supplies the fundus of the stomach, where it is known that the hormone ghrelin (one of the hormones responsible for appetite) is produced. Ghrelin is a 28 amino acid hunger stimulating peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas. Ghrelin has emerged as the first identified circulating hunger hormone. Ghrelin is also the only known circulating orexigen, or appetite enhancing hormone. Left gastric artery embolization may be a minimally invasive alternative to the current surgical treatment of gastric bypass or reduction surgery. These treatments have known serious complications including anastomotic leaks, bowel obstruction, paralytic ileus, deep vein thrombosis, pulmonary embolism, gastrointestinal bleeding, dumping syndrome, and anesthesia risks resulting in morbidity and mortality. Literature review for gastric artery embolization Transarterial embolization is a common interventional procedure used to treat a variety of medical conditions. In the image-guided procedure, an embolic, or obstructive, agent is inserted through a catheter and placed inside an artery to prevent blood flow in an artery or to a specific area of the body. Types of embolic agents include beads, coils, gel foam,as well as other materials and devices. Gastric artery embolization has been used since the 1970's to treat life threatening gastric hemorrhage. This is commonly accepted as standard of care and has been life saving for thousands of patients. It is even deemed to be effective enough to be used empirically in the setting of angiographically negative life threatening hemorrhage (as a reflection of its safety margin). Recent animal studies over the past several years in porcine and canine models have shown that gastric artery embolization results in the suppression of ghrelin levels and weight loss. 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 7 patients have been treated without complications. A recent retrospective case control study presented at the 2013 Radiological Society of North American annual meeting found that there was an average of 7.9% decrease in body weight (at 3 months) in 15 patients who underwent left gastric artery embolization for life threatening hemorrhage compared to 1.2% (P=0.001) for age matched controls (who underwent embolization other than the left gastric artery for upper gastrointestinal bleeding).

Bariatric Embolization, Gastric Artery Emboliziation, Left Gastric Artery Embolization, Morbid Obesity, Obesity, Weight Loss, Ghrelin, Embolization

Left Gastric Artery Embolization - Embolic Agent - BeadBlock 300 - 500 Micron will be used as the embolic agent to embolize left gastric artery.

Beadblock will be used intraarterially to occlude the left gastric artery and its branches. The left gastric artery supplies the fundus of the stomach, where it is known that the hormone Ghrelin (one of the hormones responsible for appetite) is produced.

Average change in body weight lost. Calculated as the average of participants: (6-Month Post-Procedure Weight in lbs.) - (Baseline Weight in lbs.)

Average change in body weight lost. Calculated as the average of participants: (12-Month Post-Procedure Weight in lbs.) - (Baseline Weight in lbs.)

Calculated as the average of participants: (((Baseline Weight in lbs.) - (6 Month Post-Procedure Weigh in lbs.))/((Baseline Weight in lbs.) - (Ideal Body Weight in lbs.)))

Calculated as the average of participants: (((Baseline Weight in lbs.) - (12 Month Post-Procedure Weigh in lbs.))/((Baseline Weight in lbs.) - (Ideal Body Weight in lbs.)))

Calculated as the average of participants: (((6-Month Post-Procedure Ghrelin levels in pg/mL) - (Baseline Ghrelin levels in pg/mL))/(Baseline Ghrelin levels in pg/mL) * 100

Calculated as the average of participants: (((12-Month Post-Procedure Ghrelin levels in pg/mL) - (Baseline Ghrelin levels in pg/mL))/(Baseline Ghrelin levels in pg/mL) * 100

Calculated as the average of participants: (((6-Month Post-Procedure Leptin levels in ng/mL) - (Baseline Leptin levels in ng/mL))/(Baseline Leptin levels in ng/mL) * 100

Calculated as the average of participants: (((12-Month Post-Procedure Leptin levels in ng/mL) - (Baseline Leptin levels in ng/mL))/(Baseline Leptin levels in ng/mL) * 100

Calculated as the average of participants: (((6-Month Post-Procedure CCK levels in pg/mL) - (Baseline CCK levels in pg/mL))/(Baseline CCK levels in pg/mL) * 100

Calculated as the average of participants: (((12-Month Post-Procedure CCK levels in pg/mL) - (Baseline CCK levels in pg/mL))/(Baseline CCK levels in pg/mL) * 100

Quality of Life (QOL): Averaged Short Form (SF)-36 Version 2 Physical Component Summary (PCS) at 6 Months Post-Procedure

The mean of participant's SF-36 Version 2 PCS at 6 months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the PCS scoring coefficient, added together, multiplied by 10 and added to 50.

The mean of participant's SF-36 Version 2 PCS at 6 months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the PCS scoring coefficient, added together, multiplied by 10 and added to 50. Changes in QOL (measured by SF-36v2 PCS) are calculated as the average of participants: (6-Month Post-Procedure SF-36v2 PCS) - (Baseline SF-36v2 PCS)

The mean of participant's 12-month post-procedure Short Form-36 Version 2 Physical Component Scores, ranging from 0-100; higher scores indicate better health status.

The mean of participant's SF-36 Version 2 PCS at 12-months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the PCS scoring coefficient, added together, multiplied by 10 and added to 50. Changes in QOL (measured by SF-36v2 PCS) are calculated as the average of participants: (12-Month Post-Procedure SF-36v2 PCS) - (Baseline SF-36v2 PCS)

The mean of participant's SF-36 Version 2 MCS at 6-months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the MCS scoring coefficient, added together, multiplied by 10 and added to 50.

The mean of participant's SF-36 Version 2 MCS at 6 months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the MCS scoring coefficient, added together, multiplied by 10 and added to 50. Changes in QOL (measured by SF-36v2 MCS) are calculated as the average of participants: (6-Month Post-Procedure SF-36v2 MCS) - (Baseline SF-36v2 MCS)

The mean of participant's SF-36 Version 2 MCS at 12-months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the MCS scoring coefficient, added together, multiplied by 10 and added to 50.

The mean of participant's SF-36 Version 2 MCS at 12-months post-procedure, ranging from 0-100; higher scores indicate better health status. The SF-36v2 contains 8 sections total which are each calculated into individual scale scores. A z-score is then determined for each scale score by subtracting the mean scale score of a sample of the national general population from the scale score of the individual participant being analyzed. Each of the 8 z-scores are then multiplied by the MCS scoring coefficient, added together, multiplied by 10 and added to 50. Changes in QOL (measured by SF-36v2 MCS) are calculated as the average of participants: (12-Month Post-Procedure SF-36v2 MCS) - (Baseline SF-36v2 MCS)

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 preprocedure. Willing, able and mentally competent to provide written informed consent (to ensure that all study subjects demonstrate an understanding of the risks of the procedure and also participate in the informed consent). 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: Less than 22 years of age Major surgery within the past eight weeks Previous gastric, pancreatic, hepatic and splenic surgery Previous radiation therapy to the left or right upper quadrant Previous gastric, hepatic, 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 one year History of severe bleeding disorder (platelet count less than 40,000) Allergy to materials in the embolic agents (acrylamido polyvinyl alcohol macromer) Enrolled in another study Any patient who has a history of allergic reaction to iodinated contrast Abnormal baseline gastric emptying study Patients taking anti-coagulants or antiplatelet drugs Patients currently taking or requiring chronic use of NSAID or steroid medications Patients with any chronic upper gastrointestinal complaints such as pain, nausea or vomiting Patients with any history of peptic ulcer disease Patients with any indication of gastrointestinal bleeding as documented by positive stool guaiac and complete blood count with abnormalities. Patients with any contraindications for monitored anesthesia care or general surgery Patients with secondary causes of obesity such as Cushing's disease and hypothyroidism Patients with active substance abuse or alcoholism Patients with defined noncompliance with previous medical care Patients with 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. Subjects with mesenteric atherosclerotic disease or abdominal angina should be excluded due to safety concerns. Patients with hiatal hernia Patients with known aortic disease, such as dissection or aneurysm Patients with comorbidity such as cancer, peripheral arterial disease or other cardiovascular disease Patients with any abnormality on their baseline EGD Patients with a CT Angiogram demonstrate an anatomical variant in left gastric artery anatomy

Data obtained through this study may be provided to qualified researchers with academic interest left gastric artery embolization for the treatment of morbid obesity. Data shared will be coded, with no PHI included. Approval of the request and is a prerequisite to the sharing of data.

Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis

Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP).

Rosch J, Dotter CT, Brown MJ. Selective arterial embolization. A new method for control of acute gastrointestinal bleeding. Radiology. 1972 Feb;102(2):303-6. doi: 10.1148/102.2.303. No abstract available.

Bookstein JJ, Chlosta EM, Foley D, Walter JF. Transcatheter hemostasis of gastrointestinal bleeding using modified autogenous clot. Radiology. 1974 Nov;113(2):277-85. doi: 10.1148/113.2.277. No abstract available.

Morris DC, Nichols DM, Connell DG, Burhenne HJ. Embolization of the left gastric artery in the absence of angiographic extravasation. Cardiovasc Intervent Radiol. 1986;9(4):195-8. doi: 10.1007/BF02577940.

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. Patel, Tarek T [corrected to Patel, Tarak H].

Paxton BE, Alley CL, Crow JH, Burchette J, Weiss CR, Kraitchman DL, Arepally A, Kim CY. Histopathologic and immunohistochemical sequelae of bariatric embolization 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.

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. doi: 10.1148/radiol.12120242. Epub 2012 Nov 30.

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. doi: 10.1007/s00270-012-0362-8. Epub 2012 Feb 25.

Brown KT, Friedman WN, Marks RA, Saddekni S. Gastric and hepatic infarction following embolization of the left gastric artery: case report. Radiology. 1989 Sep;172(3):731-2. doi: 10.1148/radiology.172.3.2788892.

Castaneda-Zuniga WR, Jauregui H, Rysavy J, Amplatz K. Selective transcatheter embolization of the upper gastrointestinal tract: an experimental study. Radiology. 1978 Apr;127(1):81-3. doi: 10.1148/127.1.81.

Bradley EL 3rd, Goldman ML. Gastric infarction after therapeutic embolization. Surgery. 1976 Apr;79(4):421-4.

Prochaska JM, Flye MW, Johnsrude IS. Left gastric artery embolization for control of gastric bleeding: a complication. Radiology. 1973 Jun;107(3):521-2. doi: 10.1148/107.3.521. No abstract available.

Robbins SM, Tuten TU, Clements JL, Fekete P. Angiographic diagnosis of gastric volvulus with report of a complication following left gastric artery embolization. Gastrointest Radiol. 1988;13(2):112-4. doi: 10.1007/BF01889038.

Miller DL, Balter S, Cole PE, Lu HT, Schueler BA, Geisinger M, Berenstein A, Albert R, Georgia JD, Noonan PT, Cardella JF, St George J, Russell EJ, Malisch TW, Vogelzang RL, Miller GL 3rd, Anderson J; RAD-IR study. Radiation doses in interventional radiology procedures: the RAD-IR study: part I: overall measures of dose. J Vasc Interv Radiol. 2003 Jun;14(6):711-27. doi: 10.1097/01.rvi.0000079980.80153.4b.

Syed MI, Morar K, Shaikh A, Craig P, Khan O, Patel S, Khabiri H. Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically (GET LEAN): Six-Month Preliminary Data. J Vasc Interv Radiol. 2016 Oct;27(10):1502-8. doi: 10.1016/j.jvir.2016.07.010. Epub 2016 Aug 24.