Study Title: Bariatric Embolization of Arteries for the Treatment of Obesity (BEAT Obesity) NCT02165124 PI: Clifford R Weiss, M.D. Date: 12/17/2015 ORIGINAL APPLICATION FOR INVESTIGATIONAL DEVICE EXEMPTION (IDE) Feasibility and Safety Study: Bariatric Embolization for Suppression of Ghrelin Level to Induce Weight Loss July 31, 2015. UPDATED for JHU IRB 12/17/2015 Study Sponsor: Aravind Arepally, M.D., FSIR Division of Interventional Radiology Piedmont Healthcare Principal Investigator: Aravind Arepally, M.D., FSIR 1984 Peachtree Road Suite 505 Atlanta, Georgia 30309 Co-Principal Investigator Clifford R. Weiss, M.D Dara L. Kraitchman, V.M.D., Ph.D., F.A.C.C. Interventional Radiology Center Cardiovascular Interventional Section Head Department of Radiology Division of MR Research 1800 Orleans Street Russell H. Morgan Department of Radiology & The Johns Hopkins Hospital Radiological Science Sheikh Zayed Tower, Suite 7203 Johns Hopkins University Baltimore, MD 21287 600 N. Wolfe Street Park Building 314 Baltimore, MD 21287 Aaron Fischman MD Rahul Patel MD Asst. Professor of Radiology and Surgery Asst. Professor of Radiology and Surgery 1 Gustave Levy Place 1 Gustave Levy Place Box 1234, Dept. of Radiology Box 1234, Dept. of Radiology Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai New York, NY 10029 New York, NY 10029 Study Monitors: Clinical Research Center at Johns Hopkins Medical Institutes Study Reference Number: Q130530 Study Sponsor: Aravind Arepally, M.D., FSIR Division of Interventional Radiology Piedmont Healthcare Table of Contents 1 Introduction ........................................................................................................ 4 1.1 Study Title .................................................................................................................4 1.2 Sponsor ....................................................................................................................4 1.3 Background / Clinical Rationale ................................................................................4 1.3.1 Stomach is an Endocrine Organ .........................................................................4 1.3.2 Anatomy of the Gastric Fundus ..........................................................................4 1.3.3 Ghrelin Suppressed after Gastric Bypass Surgery ..............................................5 1.4 Study Synopsis .........................................................................................................5 2 Device Description ............................................................................................. 6 2.1 Introduction ...............................................................................................................6 2.2 Design ......................................................................................................................6 2.3 Regulatory Status .....................................................................................................6 2.4 Anticipated Modifications to the Device and Instrumentation .....................................6 3 Report of Prior Studies ...................................................................................... 7 3.1 Pre-Clinical Studies ...................................................................................................7 3.1.1 Bariatric Embolization with Sclerosing Agent ......................................................7 3.1.2 Bariatric Embolization with Calibrated Spheres ..................................................7 3.1.3 Bariatric Embolization with Calibrated Spheres -Histology ..................................8 3.1.4 Limitations of Prior Studies .................................................................................9 3.1.5 Summary of Animal Studies .............................................................................10 3.2 Clinical Studies .......................................................................................................10 3.2.1 Bariatric Embolization of Arteries for the Treatment of Obesity: 30 Day Results from the Initial IDE Study ..............................................................................................10 3.2.2 First in Man presentation at American College of Cardiology ............................13 3.3 Bibliography of Published Studies ...........................................................................14 4 Investigational Plan .......................................................................................... 17 4.1 Purpose ..................................................................................................................17 4.2 Protocol ..................................................................................................................18 4.2.1 Study Design ....................................................................................................18 4.2.2 Patient Selection ..............................................................................................18 4.2.3 Pre-Treatment Evaluations and Data Collection ..............................................21 4.2.4 Treatment .........................................................................................................23 4.2.5 Post-Treatment .................................................................................................24 4.2.6 Post-Treatment Follow-up ...............................................................................24 4.2.7 Adverse Events ................................................................................................26 4.2.8 Subject Removal from the Study ......................................................................26 4.3 Scientific Soundness ...............................................................................................27 4.3.1 Study Design ....................................................................................................27 4.3.2 Justification of Sample Size ..............................................................................28 4.3.3 Statistical Analysis – Endpoint Assessments ....................................................28 4.3.4 Data Collection / Case Report Forms ..............................................................28 4.3.5 Adverse Event Reporting ..................................................................................28 4.3.6 Data Safety Monitoring Board (DSMB) .............................................................29 4.4 Risk/Benefit Analysis ..............................................................................................29 4.4.1 Gastric Ulceration from Bariatric Embolization: .................................................29 4.4.2 Increased Radiation Dose in Obese Patients....................................................30 4.4.3 Non target vascular embolization ......................................................................30 4.4.4 Potential Benefits and Study Justification .........................................................31 4.5 Administrative and Regulatory Considerations ........................................................31 4.5.1 IRB Review.......................................................................................................31 4.5.2 Informed Consent .............................................................................................31 4.5.3 Confidentiality ...................................................................................................31 4.5.4 Monitoring ........................................................................................................32 4.5.5 Compliance ......................................................................................................33 4.5.6 Training/ Investigator Qualifications ..................................................................33 4.5.7 Records Retention ............................................................................................33 5 Methods, Facilities, and Controls Used for Manufacturing .......................... 34 6 Investigators ..................................................................................................... 35 6.1 List of Investigators .................................................................................................35 6.2 Agreement and Certification ....................................................................................36 7 Institutional Review Boards and Certification ............................................... 42 8 Promotion ......................................................................................................... 43 9 Environmental Analysis Report ...................................................................... 44 10 Labeling .......................................................................................................... 45 11 Informed Consent Documents ...................................................................... 46 12 References Cited ............................................................................................... 47 12 RESEARCH PARTICIPANT INFORMED CONSENT AND PRIVACY AUTHORIZATION FORM ...................................................................................... 60 1 INTRODUCTION 1.1 Study Title Feasibility and Safety Study: Bariatric Embolization for Suppression of Ghrelin Level to Induce Weight Loss 1.2 Sponsor Aravind Arepally, M.D., FSIR Division of Interventional Radiology, Piedmont