Mustafa W. Aman, M.D. Director, Bariatric Surgery Program...

09/16/2017

presented by:

Mustafa W. Aman, M.D. Director, Bariatric Surgery Program

Guthrie Robert Packer Hospital

• I have no financial disclosures pertaining to any commercial interests

• Describe the role of the various Intra-gastric balloon

systems in the management of morbidly obese patients

• Discuss V-Bloc therapy as a minimally invasive surgical

weight loss option

• Highlight additional emerging modalities / treatments for weight loss

Source: Behavioral Risk Factor Surveillance System, CDC.

4

Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory, BRFSS, 2016

Adjustable Gastric

Band Sleeve

Gastrectomy Roux-en-Y Gastric

Bypass

• All procedures performed laparoscopically (minimally invasive fashion)

Source: American Society for Metabolic & Bariatric Surgery. Available online at: https://asmbs.org/resources/estimate-of-bariatric-surgery-numbers

• Balloon placed endoscopically, and filled with

saline or air

• Designed to occupy room in the stomach

• Stays inflated for a few months (6 month max)

• Causes increased sense of satiety

• Decreased gastric emptying

Not a new concept! First described by Nieben in 1982

• When first developed in 1980s, the balloons were

inflated with air • The balloons never gained popularity due to a number of

issues / complications that arose: • Insufficient weight loss

• Patient intolerance (nausea, vomiting, abd pain)

• Difficulties with attempts to inflate or deflate the balloon

• Spontaneous (unintended) balloon deflation

• Less common but more serious complications occurred: • Gastric ulcers

• Gastric perforation

• Small bowel obstruction

• In 1987, an expert panel convened to review the outcomes associated with the gastric balloon

• Focus was on improving safety and reducing adverse events associated with the balloon

• Designed to be filled with saline

• Some are also designed to have Methylene Blue Dye

• If balloon should inadvertently rupture Methylene blue dye is absorbed and patient’s urine changes color

• Patient then presents for endoscopic removal before balloon goes into small bowel

• Deployed endoscopically, with easy inflation and deflation

• Procedure time = approximately 15 mins

• Three currently FDA-approved balloon systems: • ReShape Integrated Dual Balloon System (Reshape Medical) • ORBERA Intragastric Balloon System (Apollo Endosurgery) • Obalon Balloon System

• Manufactured by Apollo Endosurgery,

Austin, TX, USA

• Made from silicone elastomer

• Designed to be filled with 400 – 700mls of saline

• Has been used outside U.S. for over 20 years. Over 220,000 placed worldwide

• FDA-approved in 2015

• Approved in U.S. for patients with BMI of 30 – 40 kg/m2

• Manufactured by ReShape, San Clemente,

USA

• FDA-approved in 2015

• Approved for patients with BMI of 30 – 40 kg/m2 with an obesity-related comorbidity

• Made from silicone elastomer

• Designed to be filled with 750 – 900mls of

saline mixed with methylene blue dye

• Over 12,000 Reshape balloons have been placed

• Balloon should be removed 6 months post-placement

• Removed endoscopically (outpatient procedure)

• Balloon punctured fluid aspirated deflated balloon grasped with an endoscopic grasper and removed

• Multicenter, prospective, randomized, non-blinded comparative study • Patients with BMI of 30 – 40 were randomized in a 1:1 fashion to:

• ORBERA treatment group placement (ORBERA placement + 12-month behavioral

modification program), versus

• Control group (12-month behavioral modification program)

• Study participants in ORBERA group had balloon removed at 6 months, with regular follow up visits continuing through 1 year postop

• Primary study endpoint = mean percent excess weight loss at 9 months

• Secondary study endpoint = percent of ORBERA patients with significant excess weight loss as compared to control group

• Prospective, sham-controlled, double-blinded, randomized, multicenter clinical

trial

• Patients enrolled between August 2012 – February 2013

• Study participants were adults aged 21 – 60 years of age

• BMI 30 – 40 with one or more obesity-related comorbidities

• Patients randomized to: • Endoscopic DBS (Dual Balloon System) + DIET (Diet and Exercise Program), versus • Sham endoscopy + DIET (Diet and Exercise Program)

• Patients in DBS arm had balloon removed at 24 weeks, followed by additional 24 weeks of counseling

• Patients in DIET arm had 52 weeks of Diet and Exercise counseling

• Primary endpoints = percent excess weight loss and DBS response rate

Exclusions: Limited to individuals with clinically significant conditions of the GI tract that would prevent safe placement of the balloon LTFU = Lost to Follow UP

Baseline demographic and clinical characteristics for the groups were comparable

DUO group (balloon treatment group) had higher weight loss than DIET group This difference reached statistical significance

• Study demonstrated that the RESHAPETM Integrated Dual Balloon System is significantly more effective than diet and exercise alone in causing weight loss

• Study participants experienced a low adverse event profile

• Overall, data suggests that the intra-gastric balloon is an effective tool for

weight loss

• Must be utilized in combination with a structured diet and exercise program

• Most of the weight loss occurs in the first 3 months post balloon placement

• In the first 3 months patients usually lose about 12kg (~26.4 pounds)

• At 6 months, estimated percent excess weight loss = 24%

• Data on long-term maintenance of weight loss is limited at this time

• Current Clinical Applications:

• Short-term weight loss before other bariatric surgeries

• Short-term weight loss before other surgeries (eg: hip arthroplasty)

• May be a reasonable option in patients who are not candidates for bariatric surgery

• Limitations: • Significant side effects in first few weeks after placement (nausea, vomiting,

abdominal pain). Typically requires significant anti-emetic and PPI use

• Limited long-term data

• Very little improvement in obesity-related comorbidities

• Lack of insurance coverage

• Vagus nerve plays a significant role in regulation of gastric functions (fundic relaxation,

antral contractions, and gastric emptying)

• VBLOC is a new treatment modality designed to induce intermittent intra-abdominal vagal blockade using high frequency electrical energy

• Two C-shaped electrodes are placed on the right and left branches of the vagus nerves around the GE junction

• Electrodes connected to rechargeable neuroregulatory device located under the skin

• VBLOC delivers signals for 12 or more hours daily at a frequency of 5000 Hz, amplitude between 3-8mA; and a duty cycle (5 mins blocked and 5 min unblocked)

• Patients are required to recharge the device for 60 – 90 minutes twice a week, using an external coil

Electrodes placed around anterior and posterior vagus nerves, and these are connected to a regulator that sits underneath the skin

• Randomized, prospective, double-blind, multi-center trial of vagal blockade

• 503 patients enrolled at 15 centers in the U.S. and Australia

• 294 patients implanted with the device and randomized to:

• Treatment with the Vbloc therapy (n = 192)

• Control group (n = 102)

• Main outcome measures: • Percent excess weight loss (EWL) at 12 months

• Serious adverse events

• Regular safety checks conducted for device-related complications in both groups

• Results: • % EWL at 12 months in treatment group = 17% +/- 2%

• % EWL at 12 months in control group = 16% +/- 2%

• No mortality • Conclusion:

• Study failed to demonstrate any meaningful increase in weight loss in the treatment group

• Randomized, double-blind, sham-controlled clinical trial on vagal blockade for weight loss

• Study conducted at 15 centers in the U.S. and Australia

• The 12-month, blinded portion of the study was completed in 2013

• 239 patients with BMI of 40 – 45, or BMI 35 – 40 with at least one obesity-related

comorbidity • Treatment group (n = 162)

• Control group (n = 77)

• Main outcome measures: • Target of mean percent excess weight loss (EWL) in treatment group to exceed sham group by

a 10-point margin, with at least 55% of patients in vagal block group achieving a 20% excess weight loss and 45% achieving a 25% excess weight loss

• Target < 15% Serious adverse events

• Conclusions of the ReCharge Clinical Trial

• Study failed to meet the pre-specified weight loss targets, however…

• It did show a statistically significant increase in weight loss amongst patients treated with the vagal nerve blockade as compared to the control group

• This study looked at the 24-month outcomes of patients in the ReCharge Trial

• Also looked at improvements in obesity-related comorbidities (HTN,

HLD, Prediabetes, and Metabolic Syndrome)

• Overall, study findings demonstrated that patients treated with vBloc therapy maintained about 21% EWL at 2 years follow up

• There was modest improvements in obesity-related comorbidities

(HTN, HLD, Prediabetes, and Metabolic Syndrome)

• Low rate of significant adverse events

• VBLOC therapy has been shown to result in statistically significant excess weight loss at 1 year compared with a control group in 1 of 2 prospective, randomized clinical trials

• VBLOC therapy has been shown to be reasonably safe, with a low complication profile. Most common side effects were GI symptoms (nausea, belching, and heartburn). Most serious reported complication was a perforation at the GE junction (one case)

• More long-term data is needed before this becomes widely accepted in bariatric

surgery practice, and before third party payors will cover cost of the procedure

• Laparoscopic Gastric Plication:

• One multicenter clinical trial

• Investigational

• Not FDA approved

• Variety of Endoscopic Interventions:

• Endoscopic Sleeve Gastroplasty

• Apollo Group Eagle Claw / Overstitch

• Endoscopic stenting

• Aspire – controversial

Laparoscopic Gastric Plication

Endoscopic Sleeve Gastroplasty

Patient-controlled emptying of gastric contents prior to digestion!

• Ali MR, Moustarah F, Kim JJ, et al. American Society for Metabolic &

Bariatric Surgery Position Statement on Intra-Gastric Balloon Therapy Endorsed by the Society of American Gastrointestinal & Endoscopic Surgeons. Surgery for Obesity & Related Diseases. 12 (2016); 462 – 467

• Papasavas P, Chaar ME, Kothari SN. American Society for Metabolic & Bariatric Surgery Position Statement on Vagal Blocking Therapy for Obesity. Surgery for Obesity & Related Diseases. Mar 2016. Vol 12, Issue 3, Pages 460 – 461.

• FDA Review of ORBERA U.S. Clinical Trial, IB-005. Available online at: https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140008c.pdf

• Ponce J, Woodman G, Swain J, et al. The REDUCE Pivotal Trial: A

Prospective, Randomized, Controlled Pivotal Trial of a Dual Intra-Gastric Balloon for the Treatment of Obesity. Surgery for Obesity and Related Diseases. 11 (2015); 874 – 881.

• Sarr MG, Billington CJ, Brancatisano R, et al. The EMPOWER Study: Randomized, Prospective, Double-blind, Multicenter Trial of Vagal Blockade to Induce Weight Loss in Morbid Obesity. Obesity Surgery. Nov 2012. Vol 22, Issue 11, p 1771 – 1782.

• Ikramuddin S, Blackstone RP, Brancatisano A, et al. Effect of Reversible Intermittent Intra-abdominal Vagal Nerve Blockade on Morbid Obesity: the ReCharge Randomized Clinical Trial. JAMA 2014;312(9):915–22.

• Apovian CM, Shah SN, Wolfe BM, et al. Two-Year Outcomes of Vagal Nerve

Blocking (vBloc) for the Treatment of Obesity in the ReCharge Trial. Obesity Surgery. 2017. 27: 169 – 176.

• Kumar N, Sullivan S, Thompson C. The Role of Endoscopic Therapy in Obesity Management: Intra-gastric Balloons and Aspiration Therapy. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. July 6th, 2017.