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  • Using Interventional Radiology to Treat Obesity—Clinical Trial Emanating from Research Resident Grant Begins this Summer

  • According to the Centers for Disease Control and Prevention (CDC), approximately 190 million Americans are overweight, obese, or morbidly obese, and this number continues to rise. Obesity negatively affects general health and has been attributed to numerous chronic conditions and various cancers. Can interventional radiology play a role in the treatment of obesity?

    AN IDEA IS BORN

    In 2009, vascular/interventional radiology resident Ben E. Paxton, M.D., and attending interventional radiologist Charles Y. Kim, M.D., of Duke University Medical Center, were intrigued by a Radiology manuscript they reviewed during a department journal club meeting. The manuscript, “Catheter-directed Gastric Artery Chemical Embolization Suppresses Systemic Ghrelin Levels in Porcine Model”— co-authored by Aravind Arepally, M.D., and Dara L. Kraitchman, VMD, Ph.D., of Johns Hopkins University, described a minimally invasive bariatric procedure to manipulate ghrelin levels and alter weight gain via chemical embolization of the arterial supply to the fundus of the stomach in pigs.

    R&E FOUNDATION SUPPORT

    Dr. Paxton and Dr. Kim formulated a research plan to build upon Dr. Arepally’s experimental design in a manner that could be more easily translatable to the clinic. Dr. Paxton reached out to Dr. Arepally to learn more about the current state of his research on bariatric embolization and future directions. “We asked Dr. Arepally to join our research team, given his experience on the topic, and thus began a collaborative project at Duke University that started with our 2010 Toshiba America Medical Systems/RSNA Research Resident Grant project, ‘Catheter directed Gastric Artery Embolization for Long Term Modulation of Systemic Ghrelin Levels in a Porcine Model’,” said Dr. Paxton.

    Dr. Kim served as the scientific advisor on that project. “I initially performed and subsequently trained Dr. Paxton on the techniques for performing the gastric artery embolization procedures in pigs, resulting in Dr. Paxton attaining embolization skills far beyond that of any resident-level trainee,” said Dr. Kim. “Dr. Arepally, as the initial pioneer that first investigated the role of interventional methods for modulating appetite, served as co-scientific advisor and provided invaluable insight and experience throughout the project – in fact, he was the only expert in existence who had published on this specialized topic that was in its infancy.”

    Six animals underwent bariatric embolization performed by the infusion of 40μ calibrated microspheres selectively into the gastric arteries that supply the fundus, while six controls underwent a sham procedure with saline. The results were clear; bariatric embolization of the stomach fundus can significantly suppress the appetite hormone, ghrelin, and significantly impact weight loss (see Figure 1). Dr. Kim recalls, “The three of us jointly analyzed the fascinating data that supported our hypothesis that embolization-induced focal ischemia to the gastric fundus diminishes the serum levels of the hunger hormone ghrelin by reducing the number of functional ghrelin-producing cells. However, the heart and soul of the project was RSNA Research Resident Grant recipient Dr. Paxton.”

    The results of Dr. Paxton’s Research Resident Grant project were published in both Radiology and the Journal of Vascular Interventional Radiology.

    ADDITIONAL NIH FUNDING

    Using Dr. Paxton’s initial research, the collaboration continued with Dara L. Kraitchman, VMD, Ph.D., and Clifford Weiss M.D., of Johns Hopkins University, obtaining funding for additional animal studies through an NIH-R01 grant mechanism. The project uses preliminary data from both Duke University and Johns Hopkins as grounds for their study. This phase of the study aims to improve bariatric arterial embolization by using advances in technology including specialized injection devices, X-ray visible embolic beads, and state-of-the-art X-ray imaging systems in order to produce a more complete fundal embolization with fewer adverse effects from non-target embolization and mucosal damage.

    CLINICAL TRIAL TO START THIS SUMMER

    Next, the collaborative group decided to pursue clinical application. After extensive discussions with the Food and Drug Administration (FDA), the Bariatric Embolization of Arteries for Treatment (BEAT) Obesity clinical trial Investigational Device Exemption (IDE) application received clearance in February. The clinical trial, supported in part by a research grant from Siemens Healthcare, will begin in August. Most recently, the clinical team was also expanded to include Rahul S. Patel, M.D., and Aaron M. Fischman, M.D., of Mount Sinai Hospital.

    Dr. Arepally, Dr. Weiss, Dr. Fischman, Dr. Kim, Dr. Kraitchman, Dr. Patel, and Dr. Paxton, are all co-investigators on the project.

    “This study will evaluate the feasibility, safety and efficacy of Bariatric Embolization in morbidly obese patients with follow-up for one year post embolization,” said Dr. Arepally. “The primary endpoints of this study are weight loss (absolute weight change from baseline and the percentage of excess weight loss [%EWL]) and 30 day adverse events. Our overall goal is to develop the first image-guided minimally invasive therapy targeting obesity. The successful development of such a technique would have enormous impact on healthcare costs and patients worldwide. The collaboration has been essential to all of our progress to date, and the group plans to continue this approach as they move to larger, phase II/III studies.”

    The R&E Foundation is pleased to see the initial work of these talented and committed investigators evolve to the point of a potential care alternative for many patients’ ongoing battles against obesity.

    PROJECT COLLABORATORS Seated left to right: Aravind Arepally, M.D., Radiology Associates of Atlanta at Piedmont Healthcare; Ben E. Paxton, M.D., Yavapai Regional Medical Center; Charles Y. Kim, M.D., Duke University Medical Center; and Rahul S. Patel, M.D., Icahn School of Medicine at Mount Sinai, Standing left to right: Clifford R. Weiss, M.D., Johns Hopkins University; Aaron M. Fischman, M.D., Icahn School of Medicine at Mount Sinai; and Dara L. Kraitchman, V.M.D., Ph.D., Johns Hopkins University. Photo used with permission of the Society of Interventional Radiology © 2014
    Figure 1 (a) Non-treated Control
    Figure 1 (b) Post Bariatric Embolization - Decreased numbers of ghrelin-producing cells seen after bariatric embolization compared to normal levels in non-treated control.