Title: Left gastric artery embolisation for weight loss in obese patients with BMI 35-50kg/m2: EMBIO trial
Funder: Department of Health and Social Care

Abstract: Aims: To determine if embolization of the left gastric artery leads to greater weight loss in patients with a BMI between 35 and 50 kg/m2 compared to a control group undergoing a sham embolization procedure. Design: Double blind (to patients and assessors) RCT. Population: Patients attending Bariatric clinics at two NHS Trusts. Inclusion criteria: Adults aged 18-70, BMI 35-50Kg/m2, ability to lie supine, willing and able to provide informed consent. Exclusion criteria: Weight >150kg, known renal, vascular or aortic disease, malignancy, prior major abdominal surgery, prior gastric or bariatric surgery, CT scan demonstrating anatomy that would make it unsafe or unsuitable for effective LGAE, prior abdominal radiotherapy, GI bleeding, chronic NSAID use, allergy to iodinated contrast, bleeding diathesis, known gastric ulceration, positive helicobacter breath test and positive pregnancy test. Intervention: Left gastric artery embolization versus Sham procedure. Both groups will receive standard Tier 3 Weight management service and screening CT scans. Primary Outcome: Absolute difference in percent weight loss. Secondary Outcome: Changes in appetite by measuring: Gut hormones (Ghrelin, PYY, GLP-1, Oxyntomodulin), Hunger and satiety scores (VAS) and Food intake (Diaries and meal test, Delay in gastric emptying (paracetamol test). Improvement in obesity related comorbidities (blood pressure, HbA1c, fasting glucose and insulin, cholesterol). Quality of life. Frequency of adverse events. Patient’s preference of treatment arm. Assessment schedule: Screening, Baseline, 3, 6, 12M Visits. Sample size: total 76 patients. In a previous weight management trial [1], investigating a drug for weight loss in patients with BMI>27, patients experienced a % change in body weight (loss) of -8.0±6.7 in the intervention arm compared to -2.6±5.7 in the control arm at 56 weeks. We consider this effect size to be clinically important. In order to see this effect size we calculate that 68 participants in total (34 per group) will have 90% power to detect a difference in percentage change in weight loss of 5.4. Assuming a 10% loss to follow up, we are aiming to recruit 76 patients in total (38 per group). Any treatment that causes >5% weight loss is clinically significant. A large proportion of obese individuals with NIDDM, hypertension, and hyperlipidemia experience positive health benefits with modest weight loss [2-5]. Statistical Analysis Plan: The primary analysis will estimate the difference between the groups mean percent weight loss and the 95% CI using a two-sample t-test. Regression, adjusted for baseline values, will investigate the relationship between percent weight loss and one or more independent variables like age, baseline BMI, diabetes, number of comorbidities and weight loss achieved on tier 3 at 12 months. A linear mixed model, taking into consideration the repeated measures over time, will be used to obtain an estimate for the mean difference in percent weight between the two treatment groups. Projected timetable: Total: 3 years. 6M Setup. 12M Recruitment. 12M Follow Up. 6M Closeout. Recruitment rate is based on the number of interventions that can be delivered at both sites

Lay abstract: Obesity is a major health issue with high costs both to patients (associated health problems like diabetes, heart disease and cancer) and society in general. Current treatments include dietary advice under the supervision of specialist dieticians, drugs, and even surgery. The most effective treatment we have is surgery, but this is quite an extreme treatment, is not suitable for all patients, is not wanted by all patients and is expensive. There is therefore a great need to develop new treatments which are more effective, less invasive and more cost-effective. Recent studies in animals and humans have shown that if the blood supply to the top of the stomach (referred to as the gastric fundus) is reduced, this results in a drop in the level of an appetite-stimulating hormone (chemical signal) called Ghrelin [6-9]. We can do this in patients using a procedure called a left gastric artery embolization which is a minimally invasive procedure with little if any discomfort to the patient. It is usually performed using local anaesthetic in the hospital catheter lab room, and often takes less than 1 hour, with a short 2 hour observation period afterwards. This embolization procedure has been done safely for the last 4 decades as a treatment for bleeding stomach ulcers. Indeed, it has been shown that patients having stomach embolizations for bleeding stomach ulcers lose more weight than patients having embolisations to other organs or other areas of the stomach. Therefore, left gastric artery embolization is a promising treatment for obesity. In order to investigate whether this could be an effective and safe technique to help with weight loss, we propose to study obese patients in a randomised controlled trial where patients undergoing embolization are compared to those undergoing a "sham" procedure. The latter involves going through the entire procedure of an embolization, with the key exception that the small beads used for embolization will not be injected. The trial participants and all the staff except the operating team will be blinded, i.e. they will not be aware as to whether a real embolization or a sham embolization has been performed. This is necessary so that we can know whether any weight loss or any side effects are due to the procedure or not. The interventional radiologist performing the procedure will not be blinded but will exert discretion and confidentiality in the procedural outcome. The trial will also involve dietary and exercise advice under the supervision of a specialist dietician and an obesity medicine physician as part of the hospital routine treatment. We will also ask trial participants to come in for some study visits, where we will assess how hormone levels change in response to a meal, how quickly the stomach empties, and check for any changes to appetite and diet. The trial participants will be followed up on a regular basis for 12 months. If we are able to show that gastric artery embolization is an effective treatment for obesity, this would open up more opportunities for the treatment of patients with obesity, thus improving their health.

Research activity codes: 5.4 SURGERY;6.4 SURGERY
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE