Endoscopic Therapies for Weight Loss

Fig. 14.1

The left image shows a digital model of the device obstructing the pylorus, and the right image shows intermittent migration that allows chyme to pass at a slower rate. (Images taken with permission from video at original site at: https://baronova.com/technology/baronova-products/)

SatiSphere System

The SatiSphere Duodenal Insert (EndoSphere Inc., Columbus, Ohio, USA, Fig. 14.2) is an endoscopically implanted device designed to delay passage of nutrients through the duodenum. It consists of a nitinol backbone with two pigtails to stabilize the device between the pylorus and duodenum and a series of polyethylene terephthalate spheres attached to the backbone that slows down the flow of chyme in the duodenum. The theoretical benefits of this device relate to hormonal regulation and are twofold: first, the spheres and increased chyme in the duodenum from slower passage may cause increased mechanical stimulation of duodenal walls, resulting in earlier satiety. Second, delayed passage in the duodenum may also cause prolonged neurohormonal signaling (i.e., CCK and GLP-1) to promote extended appetite suppression. An initial small randomized controlled trial of 31 (2:1 ratio for intervention arm) patients showed a significant excess weight loss of 18.4% at 3 months for those who completed the study (n = 9) versus 4.4% in the control group [9]. However, 10 out of the 21 patients who received the device resulted in migrations before the 3-month period, with two requiring surgical removal, and thus the trial was prematurely terminated. Device modifications have since been made to address issues with migration.

../images/442926_1_En_14_Chapter/442926_1_En_14_Fig2_HTML.jpg — Fig. 14.2

Left image shows a digital model of the SatiSphere system in the duodenum after deployment, with a magnified image on the right. (Original images taken with permission from https://www.e-sciencecentral.org/articles/?scid=SC000010392)

Full Sense Device

The Full Sense Device (BFKW LLC., Grand Rapids, Michigan, Fig. 14.3) is a modified esophagogastric stent with the intent to induce satiety. It has two components, a cylindrical stent placed above the gastroesophageal junction that is connected to a disk situated below the junction, placing pressure on the distal esophagus and gastric cardia. Although the exact mechanism is unknown, it is thought theoretically that the mechanical pressure from the device would likely trigger gastric stretch receptors and neurohormonal signaling, which would promote a constant state of fullness and thus appetite suppression. The device is currently undergoing internal clinical trials, most recently reporting having done studies of 100 obese patients in Mexico. However, no peer-reviewed data is available to date.

../images/442926_1_En_14_Chapter/442926_1_En_14_Fig3_HTML.jpg — Fig. 14.3

Artwork of the device implanted in the distal esophagus and gastric cardia. (Original image available at: http://www.obesityhelp.com/articles/new-full-sense-device-to-combat-obesity)

Malabsorptive Sleeves

EndoBarrier

The EndoBarrier (GI Dynamics, Boston, MA, USA, Fig. 14.4) is a malabsorption bypass filter that prevents mixing of chyme and pancreaticobiliary juice and digestion in the proximal intestinal tract. The device is composed of a 60 cm fluoropolymer liner reversibly anchored to the duodenal bulb and extending to the proximal jejunum. Chyme passes from the stomach and into the EndoBarrier, while pancreatic enzymes and bile flow outside the liner. To date, dozens of multicenter clinical trials and observational studies around the world have been conducted with success in achieving excess weight loss as well as better glycemic control when combined with other diabetic therapies [10–13]. A recent meta-analysis of recent trials showed significant reduction in excess weight loss of 12.6% (95% Cl 9.0, 16.2) at 12 weeks when compared to diet changes only. In addition, the meta-analysis showed a decrease in glycated hemoglobin of 0.9% (95% Cl −1.8, 0.0) and a reduction of fasting plasma glucose of 3.7 mM (95% Cl −8.2, 0.8) [14]. Neither of the glycemic markers on aggregate reached statistical significance, although the results were close. The device so far is not FDA approved due to a 3.3% incidence of hepatic abscesses (7/212 in intervention arm) in the recent US pivotal trial, which is higher than the 2% safety threshold and thus resulted in early termination of the trial [15]. Other complications include abdominal pain and GI bleeding, each noted to occur in 3.8% (8/212) of patients in the interventional arm [14]. Overall, the EndoBarrier appears to be a promising therapeutic option for weight loss and glycemic control. Further trials are planned following device reiteration.

../images/442926_1_En_14_Chapter/442926_1_En_14_Fig4_HTML.jpg — Fig. 14.4

Artwork of the device after full deployment of the EndoBarrier sleeve. (Image is credited to original video available at: http://gidynamics.com/endobarrier/)

ValenTx Sleeve

The ValenTx Sleeve is a fluoropolymer bypass sleeve that aims to mimic the physiological benefits of a Roux-en-Y bypass, promoting early satiety and malabsorption by circumventing the stomach and proximal small bowel. The device extends from the gastroesophageal junction at the Z-line to the proximal jejunum, with a total length of 120 cm. So far, one 12-week pilot study and a follow-up year-long single-center trial have been published. The pilot study of 17 patients reported an excess weight loss of 39.7% after 12 weeks. In addition, patients taking antihyperglycemic or antihypertensive medications prior to the trial no longer required the medications at the end of the 12-week trial due to improvements in glucose control and blood pressure. Five out of the original 22 patients could not complete the trial due to early postoperative dysphagia [16]. The follow-up trial followed ten patients for a year after device placement and reported a mean excess weight loss of 36%. Four out of ten patients had a partial cuff detachment. When those patients were excluded, the excess weight loss on average was higher at 54%. The device was otherwise well tolerated [17]. A larger follow-up study of 40 patients is set to be complete by October 2018 [18].

Gastric Motility Therapies

Botulinum Toxin A Injection

Botulinum toxin injections are commonly used for patients with GI smooth muscle disorders, including achalasia, diffuse esophageal spasms, gastroparesis, and sphincter of Oddi dysfunction [19]. Over the past decade, botulinum injections have also been considered as a possible option in treating morbid obesity . Injected onto the gastric antrum, botulinum has been thought to delay gastric emptying by inhibiting peristalsis, thus helping achieve earlier satiety. There currently exist three randomized control trials that have so far explored this option, with mixed results [20]. One double-blind, randomized control trial with 24 patients showed significant weight loss (11.0 vs. 5.7 kg, p < 0.001), higher satiety, reduction in gastric capacity, and delayed emptying 8 weeks after 200 IU of botulinum injection when compared to the placebo group [21]. However, the two other studies showed no significant weight loss after 5 and 16 weeks postinjection, respectively, even at higher doses of 500 IU botulinum [22, 23]. It is unclear the reason behind these mixed results, though possibly due to the studies’ small cohort size. Due to these mixed results, botulinum injections are currently not medically indicated or FDA approved for weight loss therapy. Currently, one longer clinical trial of a cohort of 20 patients is underway to determine the benefit of repeated botulinum injections with follow-up over the span of 5 years [24]. The current study is set to be completed in 2022.

Endoscopically Placed Gastric Stimulator

Although the exact mechanism is currently unclear, implantable gastric stimulators are hypothesized to impair physiological electrical activity in the gastric system, causing delayed gastric emptying and increased satiety. Currently, multiple devices are actively undergoing clinical trials, with all studies achieving some level of statistically significant weight loss in the first 12 months [25]. At the moment, larger and longer studies are actively being pursued. However, these gastric stimulators currently require laparoscopic implantation due to the size of the device. Versions of these devices that can be endoscopically placed do exist, although they are still in the preclinical stage (Fig. 14.5) [26]. Further modifications and clinical trials of these devices will need to be conducted in the future before they can be considered as possible therapeutic options for weight loss.

../images/442926_1_En_14_Chapter/442926_1_En_14_Fig5_HTML.png — Fig. 14.5

Front and back images of a preclinical version of the device. (Original images available from Springer article Lonys et al. [26])

Intestinal Alterations

Revita Duodenal Mucosal Resurfacing

The Revita Duodenal Mucosal Resurfacing (Fractyl Laboratories, Cambridge, MA) procedure aims to improve glycemic control in diabetic patients via duodenal hydrothermal ablation . The technique for the ablation first entails a mucosal lift via submucosal saline injection to protect the deep muscularis, followed by circumferential thermal ablation (at a temperature of 90 °C) of the duodenal walls by a balloon catheter. The mucosa walls then naturally regenerate, which is hypothesized to modify enteroendocrine cell signaling and thus glycemic control and insulin resistance (Fig. 14.6). An initial trial of 39 patients was conducted, with 28 receiving long-segment (average 9.3 cm) and 11 receiving short-segment (average 3.4 cm) ablations between the ampulla of Vater and ligament of Treitz [27]. Three months post-procedure, those who received the long segment ablation saw a larger reduction in hemoglobin A1c (2.5%, from an average baseline of 9.5%) than those who received a short-segment ablation (1.2%). No significant difference was noted at 6 months, with 1.4% reduction in hemoglobin A1c for long-segment ablation and 0.7% reduction for short segment [28]. Patients also saw a reduction in their hepatic transaminases (AST 32 ± 17 from baseline to 22 ± 6 at 6 months; ALT 40 ± 23 from baseline to 27 ± 12 at 6 months), thus invoking possible benefit for fatty liver disease as well. Effects on weight loss were minimal, with a mild decrease in total weight from 86 ± 11 kg at baseline to 82 ± 11 kg at 1 month post-procedure that subsequently reverted to near baseline at 6 months [1]. Although not aimed specifically at weight loss, the procedure has shown metabolic benefits to sequelae linked with obesity and metabolic syndrome. The company is currently actively recruiting patients for a larger clinical trial with a longer follow-up of 48 weeks to further evaluate the procedure as a possible therapeutic option for type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) [29].

../images/442926_1_En_14_Chapter/442926_1_En_14_Fig6_HTML.png — Fig. 14.6

Left image shows a digital model of the ablated duodenal lining immediately after the procedure, and the right image shows regeneration of the mucosa multiple weeks after. (Original images available at: http://www.fractyl.com/medical-professionals/#revita-dmr-procedure)

Partial Jejunal Diversion Procedure Using Incisionless Magnetic Anastomosis System

The Partial Jejunal Diversion procedure is an endoscopic therapy designed to treat type 2 diabetes and obesity, performed using the Incisionless Magnetic Anastomosis System (IMAS; GI Windows, Boston, MA, USA). The procedure uses simultaneous enteroscopy and colonoscopy to place two self-assembling octagonal magnets in the jejunum and ileum, respectively. The procedure concludes with the coupling of these two magnets under endoscopic and fluoroscopic visualization. Within 1 week, a large-caliber, side-to-side anastomosis forms between the jejunum and ileum, creating a partial diversion for chyme while preserving the native pathway to mitigate against complications of malabsorption [30]. The coupled magnets are naturally expelled in the stool (Fig. 14.7). Early clinical results indicate significant durable glycemic control from changes in neurohormonal control in addition to sustained weight loss. GIW has completed their first pilot study of ten patients with reported post-procedure results up to 12 months [32]. All anastomoses formed within 1 week and continued to be patent. Mean weight loss at 6 and 12 months was 28.3% and 40.2% EWL, respectively. Seven out of ten patients were diabetic or prediabetic, and all patients received significant reduction in HbA1c (1.9% for diabetic and 1.0% for prediabetic at 12 months) and fasting blood glucose. No serious complications were noted [31, 32]. Post-procedure nausea and diarrhea were reported in some patients, with most symptoms resolving within 2 weeks and all cases resolving with diet modifications or standard medical therapy. Larger prospective trials are planned to be conducted in the future.