Bariatric Embolization of Arteries With Imaging Visible Embolics (BEATLES)
Bariatric Embolization of Arteries With Imaging Visible Embolics (BEATLES)
Obesity is defined as a body mass index (BMI) ≥30 kg/m2 and with a subclass of obesity known
 as morbid or severe obesity (BMI of ≥40 kg/m2). These are major issues in medicine for both
 participants and medical providers with >36% of the US population affected. Obesity is one of
 the biggest causes of preventable chronic diseases and healthcare costs in the USA. Obese
 adults spend 42% more on direct healthcare costs and morbidly obese adults overall have 81%
 higher healthcare costs than non-obese adults. Obesity is currently treated with dietary,
 pharmacological, and/or surgical approaches that are often unsuccessful or are associated
 with additional risks. As the incidence and prevalence of obesity and obesity-related
 diseases are steadily increasing, there is a growing need to detect the key risk factors
 involved in disease development and modify standard treatment procedures and protocols.

 The most successful long-term strategy continues to be bariatric and metabolic surgeries,
 such as sleeve gastrectomy and Roux-en-Y gastric bypass (RYGBP). The NIH recommends bariatric
 surgery for participants with a BMI of 40 kg/m2 or greater or a BMI of 35 kg/m2 or greater
 and obesity related comorbidities. These surgeries enable participants to lose between 50%
 and 75% of excess body weight. Despite this success, participants are apprehensive and do not
 undergo bariatric surgery with the biggest fear being the many complications that come with
 the procedure. Studies have shown that 57-77% of participants are not interested in bariatric
 surgery although the participants qualify.(16)

 With the concern of complications from bariatric surgery, interest in endoscopic bariatric
 techniques has increased over the years. The techniques have been shown to be efficacious,
 reversible, relatively safe, and cost effective. Further, these techniques offer a
 therapeutic window for some participants who may otherwise be unable to undergo bariatric
 surgery. The American Society for Gastrointestinal Endoscopy have approved endoscopic
 procedures, such as balloon therapy, for participants with BMI in the 30-40 kg/m2
 range.(17,18) However, the products used in these therapies also have several limitations
 primarily the inability to provide long term weight loss given the temporary nature of these
 balloons.(19) Common adverse events following intragastric balloon insertion include
 abdominal pain (33.7%), gastroesophageal reflux disease (18.3%), anorexia, and nausea (29%).
 Severe complications such as gastric ulcers (2%), small bowel obstruction (0.3%), perforation
 (0.1%), balloon migration (1.4%), and death (0.08%) are less common. Early balloon removal
 occurred in 9.1% of the study participants due to participant intolerance.(20)

 In a pilot study to assess safety and efficacy (BEAT Obesity), 20 morbidly obese participants
 with a BMI of ≥40 kg/m2 with no other comorbid conditions underwent bariatric embolization
 and were followed for 12 months. Participants were embolized with 300-500 µm Embospheres.
 None of the 20 participants in the BEAT Obesity trial (the largest prospective trial to date)
 had any major adverse events. Any gastric ulcers that occurred (40%) were asymptomatic and
 were completely healed by three months after the procedure.(21)

 There were many limitations of this study including the absence of a control cohort and
 non-compliance amongst study participants. A target population of participants with a BMI of
 40 kg/m2 and above was too high considering the bariatric embolization procedure is
 comparable to endoscopic bariatric therapies rather than bariatric surgery. BEAT Obesity
 excluded participants with comorbidities, such as those who suffer from diabetes, who may
 greatly benefit from this procedure and are often the target population for
 endoscopic/surgical bariatric therapies. A larger bead size of 300-500 µm was specifically
 chosen compared to preclinical data and prior clinical reports due to concerns of gastric
 ischemia and ulceration. However, smaller bead size produces greater weight loss and hormonal
 shifts.(22)

 Investigators hypothesize that transvascular bariatric embolization results in safe and
 effective weight loss in obese participants compared to control subjects.
The BEATLES study is an investigator-initiated, prospective, double-blinded, randomized,
 sham-controlled study that will assess the impact of bariatric embolization on the systemic
 levels of obesity-related hormones and, as a consequence, on weight loss. The goal of this
 study is to help treat obesity combining a lifestyle program and a minimally invasive,
 angiographic (i.e., through blood vessels) approach.
Inclusion Criteria:

 -  Male or female, aged ≥21 and ≤70 years

 -  Willing, able, and mentally competent to provide written informed consent

 -  Obese patients with a BMI ≥35 kg/m2

 -  Weight ≤400 lb

 -  Vascular anatomy (including celiac, hepatic, and gastric arteries) that in the opinion
 of the interventional radiologist is amendable to bariatric embolization, as assessed
 via 3D CT angiography

 -  Suitable for protocol therapy, as determined by the interventional radiology
 investigator

 -  Adequate hematologic (neutrophils>1.5x109/L, platelets>70x109/L, international
 normalized ratio (INR<1.5), hepatic (bilirubin≤2.0mg/dL, albumin≥2.5g/L), and renal
 (estimated glomerular filtration rate (GFR)>60milliliter mL/min. 1.73m2) function

 -  For females of reproductive potential: agreement to use of highly effective
 contraception

 -  for duration of study participation

 -  Patients who have failed conservative weight loss therapies such as supervised low
 calorie diets combined with behavior therapy and exercise

 -  Live or work within 65 miles of the enrolling institution in case a catastrophic post
 embolization event occurs

 Exclusion Criteria:

 -  hemoglobin A1c greater than 8%

 -  Patients who are currently taking either Insulin or sulfonylurea (medication changes
 are allowed)

 -  Prior history of gastric, pancreatic, hepatic, and/or splenic surgery

 -  Prior radiation therapy to the upper abdomen

 -  Prior embolization to the stomach, spleen, or liver

 -  Cirrhosis

 -  Known portal venous hypertension

 -  Active peptic ulcer disease

 -  Significant risk factors for peptic ulcer disease, including daily NSAID use

 -  Large hiatal hernia, defined as >5 cm in size

 -  Active H. Pylori infection

 -  Known aortic pathology, such as aneurysm or dissection

 -  Renal insufficiency, as evidenced by an estimated glomerular filtration rate of <60
 milliliter(mL)/min

 -  Major comorbidity, such as active cancer, significant cardiovascular disease, or
 peripheral arterial disease

 -  Pregnancy

 -  Pre-existing chronic abdominal pain

 -  Positive stool occult blood study

 -  GI bleeding or bleeding diathesis within 5 years

 -  Weight loss (intentional or unintentional) of more than or equal to 5% of body weight
 in the 6 months prior to randomization

 -  A weight loss greater than 6lb during the weight management run- in

 -  Use of anti-obesity medications in the 12 months prior to screening

 -  Endoscopic findings that would preclude bariatric embolization (at the discretion of
 the study team)

 -  History of gastric motility disorders or an abnormal nuclear gastric motility
 examination (to be performed in diabetic subjects only)

 -  American Society of Anesthesiologists Class 4 or 5 (very high risk surgical
 candidates: class 4=incapacitating disease that is a constant threat to life) at the
 time of screening for enrollment into the study - this exclusion criterion exists,
 because of the possibility that surgical intervention will be needed if the study
 intervention subsequently leads to severe adverse effects

 -  Inflammatory bowel disease

 -  Autoimmune disease or HIV+

 -  History of allergy to iodinated contrast media

 -  Failure to comply with pre-procedure weight management "run-in", or other
 pre-procedural visits (specifically, participants must complete 80% of weight
 management and Lose It! Food tracking, and 100% of one-time visits, i.e. MRI, computed
 tomography angiography (CTA), endoscopy)

 -  Applicability of any contraindication regarding patient's vasculature as per
 Instruction for Use

 -  Inability to have an MRI scan (i.e., metal implants or claustrophobia)

 -  Smokers/vape users/tobacco use

 -  Active or new-onset endocrine disorders (stable disease acceptable)

 -  Other unforeseen conditions that may make patients unsuitable for the procedure (study
 team discretion)

 Exclusion Criteria (Psychiatric):

 -  As determined by clinical judgment based on Clinical Interview,
 psychological/behavioral measures, medical records, previous mental health
 records/other collateral information (as available) and consistent with diagnostic and
 statistical manual of mental disorders (DSM) -5 criteria:

 -  Diagnosis of severe mental illness (i.e., chronic psychotic spectrum disorders,
 clinically significant mood disorders) AND/OR one or more of the following:

 -  Evidence of active relapse or active impairing symptoms (e.g., suicidal ideation,
 audio or visual hallucinations, paranoia, thought disturbance, severe impairment)

 -  Evidence of minimal supports or limited adherence to ongoing mental health care

 -  Failure to provide comprehensive aftercare plan that includes emergency plan for
 addressing future mental health relapse

 -  History of treatment refractory mental illness/recurrent relapse (multiple suicide
 attempts or inpatient psychiatric hospitalizations in the past 5 years)

 -  Within past 3 years: Inpatient psychiatric hospitalization

 -  Within past 5 years: Suicide attempt

 -  Declining to provide mental health records, a letter of support from mental health
 professionals, or consent for verbal consultation with mental health professionals
 when determined to be essential to evaluation.

 -  Cognitive impairment, if judged to have

 -  Limited capacity to make informed decision about procedure and inability to verbalize
 an understanding of the surgical procedure, risks and benefits.

 -  Inability to demonstrate an understanding of the permanency of lifestyle change
 required

 -  History of Anorexia or History of/Active Bulimia: If determined to be of low enough
 severity not to be a clear contraindication, minimum of 5 years abstinence from
 bulimia, current moderate to severe binge eating or night eating syndrome

 -  Active or History of Substance Abuse with less than 5 years of abstinence

 -  Current use of anti-tricyclic anti-depressants or steroids, psychiatric medications
 associated with weight gain.