This column investigates current research in the surgical and clinical aspects of obesity treatment and educates bariatric care professionals on the most up-to-date information on emerging technologies in the field.
This month: Intragastric Balloons: Closing the Gap on Weight Loss Treatment Options
by Jaime Ponce, MD, FACS, FASMBS
Chattanooga Bariatrics, Chattanooga, Tennessee
Bariatric Times. 2016;13(3):13–18.
At the end of July and beginning of August 2015, the United States Food and Drug Administration (FDA) approved two intragastric balloon systems for the treatment of obesity—the ReShape Integrated Dual Balloon System (ReShape Medical, San Clemente, California) and Orbera Intragastric Balloon System (Apollo Endosurgery, Austin, Texas). This article discusses the clinical trials evaluating the safety and effectiveness of the intragastric balloons. The author also provides an overview of how intragastric balloon systems work and discusses their role among current obesity treatments.
FUNDING: No funding was provided.
DISCLOSURES: The author reports the following disclosures relevant to the content of this article: ReShape Medical, Inc. (San Clemente, California): consultant, FDA clinical trial investigator; Obalon Therapeutics, Inc. (San Diego, California): FDA clinical trial investigator; USGI Medical, Inc. (San Clemente, California): FDA clinical trial investigator; W. L. Gore and Associates, Inc. (Flagstaff, Arizona): consultant, speaker; Olympus Corporation (Tokyo, Japan): speaker; ConMed (Utica, New York): consultant.
The use of intragastric balloons for the treatment of obesity in the United States dates back to 1985 when the United States Food and Drug Administration (FDA) approved the Garren-Edwards Gastric Bubble (American Edwards Laboratories, Irvine, California), a cylindrical-shaped device that was inserted into the stomach through the mouth and then filled with 220cc of air. The device was meant to be left in the stomach for 3 to 4 months and then removed. After the product’s approval, prospective, randomized, clinical trials showed that its use did not result in significantly more weight loss than diet and behavioral modification alone. It was also associated with a significant number of clinical complications that included erosions, migrations, and bowel obstructions. In 1992, the manufacturer (now Edwards Lifesciences) took the device off the market voluntarily.
In the early 1990s, the BioEnterics Intragastric Balloon (BIB, Inamed Health, Santa Barbara, California) was developed and approved outside of the United States. Genco et al, Sallet et al, Lopez-Nava et al, and others (see sidebar “Participants in Intragastric Balloon Research”) have demonstrated good short-term weight loss and a small percentage of complications with the BIB outside of the United States.
In 2008, a meta-analysis of 3,442 cases showed a mean BMI loss of 5.7 points and 32.1 percent excess weight loss (%EWL) with few complications, including 0.9 percent deflations, 0.8 percent obstructions, 0.1 percent perforations, and 0.1 percent mortality.
Outside of the United States, the balloon has been used successfully in patients with overweight (body mass index [BMI] ≥25–29.9kg/m2), obesity (BMI ≥30–39.9kg/m2), and morbid obesity (BMI ≥40kg/m2), and as a bridge therapy for bariatric surgery. There are several types of balloons, including air-filled, adjustable, swallowable, and excretable. Currently, two intragastric balloon devices are FDA approved in the United States: Orbera™ Intragastric Balloon System (Apollo Endosurgery Inc, Austin, Texas) and ReShape® Integrated Dual Balloon System (ReShape Medical, Inc., San Clemente, California). Both are saline-filled balloons. These devices are indicated for patients with obesity (BMI 30–40kg/m2). Intragastric balloons may fill the gap in the treatment of obesity between lifestyle modification/pharmacotherapy and bariatric surgery.
Sidebar: Participants in Intragastric Balloon Research
Procedure and Program
Procedure and Placement illustrations for ReShape Integrated Dual Balloon
Procedure and Placement Illustrations for Orbera Intragastric Balloon
Intragastric balloon systems were designed to create a feeling of fullness in the patient by occupying space in the stomach. With both Orbera Intragastric Balloon and Reshape Integrated Dual Balloon, the system is placed into the gastric cavity through the mouth during a minimally invasive endoscopic procedure while the patient is under mild sedation.
Orbera Intragastric Balloon is a weight-loss system that uses a single gastric balloon. The Reshape Integrated Dual Balloon is made up of two connected, independently sealed balloons. The balloons are filled with sterile saline and a small amount of methylene blue. They remain in the stomach for a period of six months.
The balloons in the ReShape Integrated Dual Balloon System have a fill volume of 750–900cc and are designed to conform to the natural shape of the stomach. Also, the dual balloon design reduces the potential for migration of the device from the stomach to the intestines if a balloon deflation occurs, which helps to reduce risk of intestinal obstruction. Injection of the methylene blue into the saline solution in the balloons helps to provide an indicator of balloon deflation by turning the patient’s urine blue-green and signaling the need for the patient to call the physician.[7,8]
The Orbera system is a single balloon filled with 400–700cc of saline (most commonly 550–650cc). Extensive experience internationally has shown very low rate of deflations causing migration and bowel obstruction.[6,9].
After balloon insertion, patients return to the clinic monthly for the six months the balloons are in place and for six months following balloon removal, totaling 12 months of medical supervision from an experienced bariatric multidisciplinary team. During these regular appointments, the integrated health team supports the patient in adhering to the weight loss program. They help patients develop healthy weight management skills and set goals and monitor the patients’ progress.
Outside the United States Experience
Orbera intragastric balloon has an extensive clinical history in Europe and Latin America. A recent meta-analysis of 82 international publications demonstrated a 13.1 percent total body weight loss at six months based on 6,845 patients. At 12 months, six months after balloon removal, the mean total body weight loss was 11.1 percent and excess weight loss was 25.4 percent. Nausea, vomiting, and reflux were the most common adverse events at 33.7 percent, 29 percent, and 18.3 percent, respectively. Early removal rate was 7.5 percent.
There is one article reporting international data on the dual intragastric balloon system. Lopez-Nava et al examined the effectiveness of the dual intragastric balloon among 60 patients (11 men, 49 women) with obesity (initial BMI of 38.8kg/m2) that underwent endoscopic placement of a dual intragastric balloon filled with a total of 900cc of saline (450cc in each balloon). Study participants had the balloon system in place for at least six months and received regular counseling from a multidisciplinary team. The authors observed a mean EWL of 47.1 percent and a decrease in mean BMI from 38.8kg/m2 to 32.7kg/m2. On average, patients lost 15.4 percent of their initial body weight, and the rate of early balloon removals for intolerance was two percent.
United States Experience
The Orbera Intragastric Balloon System was approved by the FDA on August 5, 2015, based on the US pivotal study. In this randomized, multicenter clinical trial for adults with a body mass index of 30 to 40kg/m2, patients were split between the Orbera Intragastric Balloon System with lifestyle modification arm and the lifestyle modification only arm. A total of 273 patients were randomized across the two groups with 137 patients receiving the balloon. Patients were followed for 12 months and were assessed at 6, 9, and 12 months. Patients who received the balloon demonstrated superior weight loss to the control arm at all time points through the pivotal study. At six months, weight loss in the balloon group was 10.2 percent of total body weight versus 3.3 percent in the lifestyle modification only group. Statistically significant differences in weight loss were seen between the balloon and the control arm at nine months (9.1% vs. 3.4%) and 12 months (7.6% vs. 3.1%).
The majority of the adverse events were mild to moderate with the most common adverse events being nausea, vomiting, and reflux. The most common severe adverse event was early removal of the device due to intolerance. The incidence rate of nausea (86.9% of patients), vomiting (75.6%), and early removals (18.8%) were higher than the international experience due to the management protocols. No balloon deflations or ulcerations were reported in the US pivotal study.
ReShape Integrated Dual Balloon System was approved by the FDA on July 28, 2015, based on the REDUCE pivotal trial. This study was a prospective, sham-controlled, double-blind, randomized multicenter United States clinical study that enrolled 326 patients with obesity and followed them for 48 weeks. Participants were between 21 and 60 years of age with a baseline BMI between 30kg/m2 and 40kg/m2. Participants also presented with one or more obesity-related comorbid conditions, including type 2 diabetes mellitus (T2DM), obstructive sleep apnea (OSA), and hypertension.
Patients were randomized into two groups. The DUO group (n=187) underwent the ReShape Integrated Dual Balloon procedure plus diet and exercise counseling. The DIET group (n=139) underwent sham endoscopy plus diet and exercise alone. DUO patients had the device removed after 24 weeks and continued with diet and exercise counseling for an additional 24 weeks. After 24 weeks, the patients in the DUO group had significantly greater weight loss than the DIET group. DUO patients had a 28 percent EWL and 2.3 times as much weight loss compared to the DIET group.
Twenty-four weeks after balloon removal, DUO patients maintained a mean of 66 percent of their initial weight loss. More than half of the subjects still had more than 25 percent EWL compared to baseline weight, and 25 percent of subjects continued to lose additional weight following device removal.
Clinically and statistically significant comorbid improvements were observed in diabetic, hypertensive, and hyperlipidemic outcomes, and these improvements were sustained through 48 weeks of follow up. Quality of life assessments demonstrated substantial improvements in subjects’ sense of well-being as measured by both obesity-specific and general instruments, and measures of patient satisfaction with the results of the procedure were high. In addition, of the patients who completed treatment, two-thirds reported that they would undergo it again, and 77 percent said they would recommend it to a friend.
Adverse events included post-implantation accommodative symptoms of nausea, vomiting, and abdominal pain. Out of 264 patients that had the dual balloon implanted, 87 percent had nausea or vomiting. These symptoms were reported as mostly mild in severity and typically subsided within 3 to 7 days. Symptoms were reported by patients using the Rhodes Index of Nausea, Vomiting, and Retching form (Rhodes Index) and an abdominal pain visual analog scale (VAS) at baseline, Day 3, and Weeks 1, 4, 12, and 24 during the REDUCE study (Figure 8 Figure 9 ).
Clinical Benefits of Intragastric Balloon Systems
In both randomized, clinical studies, the intragastric balloon resulted in better weight loss compared to diet and exercise alone. In addition to positive patient results, surgeons may find that the system offers other clinical benefits. Personally, I find that endoscopic placement of the balloon is not complicated. The stomach should be inspected and known to be normal prior to implantation, and the device can be placed and removed under conscious sedation in an outpatient procedure. I also find that since the procedure is not a traditional weight loss surgery, such as laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, and therefore does not alter the anatomy, patient acceptability is high. Patients with BMIs between 30 and 40kg/m2 may also find the intragastric balloon procedure attractive if they are not ready or do not qualify for surgery. Lastly, unlike pharmaceuticals, there is no daily decision for the patient to make about whether to follow the program, thus adherence may be improved, compared to those individuals who use lifestyle modifications alone or in combination with pharmaceuticals.
It is important for patients and practices to understand the following about intragastric balloon procedures: 1) some patients will not respond well to the device, 2) weight loss might not be significant, and 3) it needs to be used in association with a good supportive diet and lifestyle changes. Several risks and limitations should be discussed with patients when offering the balloon procedure, including the following:
1. Contraindications. Inability to place the balloon secondary to incidental findings in the stomach (i.e., ulcers, tumors, large hiatal hernia, achalasia or any other severe motility disorder).
2. Adverse events. The majority of patients will experience nausea, vomiting, and abdominal discomfort during the first few days, and some patients may require early balloon removal for intolerance. The range can be as low as two percent in some experienced practices to as high as 18 percent as was seen in the US pivotal study. Experience and patient management of expectations, education, reassurance, and medications may lower the percentage of early balloon removal. We also learned from the REDUCE trial that shorter stature patients (<5’4”) require less fluid (750cc instead of 900cc) to have lower rate of intolerance. For Orbera, smaller balloons (400cc to 500cc) may be warranted in patients with motor dyspepsia or gastroparesis.
3. Balloon deflation. Balloon deflation has become a rare event as the manufactures have improved the design of the devices, but patients and providers should remain aware of this possibility and the need for immediate removal if balloon deflates to avoid its migration.
ReShape Integrated Dual Balloon System. In the REDUCE pivotal trial, balloon deflation occurred in six percent of patients without migrations usually late in the treatment phase. Deflation in the ReShape Integrated Dual Balloon System can be detected by instructing patients to look for a change in urine color to blue-green and a decrease in the sensation of fullness after eating.
Orbera Intragastric Balloon System. In the US Pivotal Study of the Orbera Intragastric Balloon System, there were no spontaneous deflations. According to Directions for Use (DFU) for the Orbera Intragastric Balloon System, balloon deflation may be detected when patients report loss of satiety, increased hunger and/or weight gain. In these cases, patients should be examined endoscopically.
4. Ulcers. Ulcers can occur in 2 to 10 percent of patients. These are usually small and superficial, but patients should be aware of the need to take proton-pump inhibitors (PPI) during the six-month balloon therapy.
I became interested in the intragastric balloon as I witnessed it being used internationally. I had the opportunity to visit Dr. Manoel Galvao-Neto in Sao Paulo, Brazil, and discuss the procedure in length with him and others. Less than one percent of the individuals with obesity and morbid obesity are having bariatric surgery. Many patients that are struggling with obesity and have BMIs between 30 and 40kg/m2 are not seeking treatment via bariatric surgery. Some reasons for not seeking treatment may include not being ready or being afraid. Many patients have maximized different diet plans and pharmacotherapy, and we didn’t have anything else to offer them.
The endoluminal therapies, like the intragastric balloon, helps to fill the gap between lifestyle/diet and pharmacoptherapy and surgery, especially for the patient population with BMIs 30 to 40kg/m2. These therapies may attract patients to our practices and allow them to undergo effective treatment for their obesity.
My endoscopic skills were sufficient, and I was offered the opportunity to participate and be the principal investigator for the REDUCE pivotal trial.
After FDA approval, we have seen significant enthusiasm by the bariatric surgery community, and patients that followed the news segments in the media asked for this therapy. We decided to develop all the necessary clinical care pathways, structured a one-year comprehensive program, and placed the first ReShape Integrated Dual Balloon after FDA approval on September 1, 2015. (Figure 10 ). My colleague, Dr. Abu Dayyeh from Mayo Clinic, Rochester, Minnesota, placed the first Orbera balloon after FDA endorsement on August 14, 2015.
During the clinical trials and exposure to international experience with the balloon, I have learned that intolerance is very variable among centers and very dependent on expertise. Early removals in international publications are 7.5 percent, and some centers have early removal rates as low as two percent. Even in the US clinical trials, the range of early removals varied significantly among all the centers. Many centers around the world have abandoned the intragastric balloon as it has not offered adequate results for their patients. The most important thing I have learned is that the balloon is not “magic.” It is only a supportive instrument for a well-structured comprehensive diet and exercise program. The majority of patients that follow the comprehensive program with a balloon will lose more weight, but not all. Also, a significant number of patients will likely experience weight regain. In these case, patients will need to continue to address the obesity by considering either a sequential balloon or bariatric surgery if they qualify.
The future for endoluminal bariatric therapies looks promising as the FDA is evaluating several procedures. On the balloon technologies front, we have two other devices that are undergoing US clinical trials: the Obalon balloon (Obalon Therapeutics, Inc., San Diego, California) and the Elipse balloon (Allurion Technologies, Wellesley, Massachusetts)
The Obalon balloon includes a small capsule attached to a tube. The patient swallows the capsule with a glass of water. No sedation is required. Gas is used to inflate the balloon, and the tube is removed. Up to 3 balloons can be placed to continue to facilitate weight loss over the six-month treatment. At the end of this period, the balloons are removed in a short endoscopic procedure in which the patient is placed under sedation.
The Elipse balloon is also delivered in a swallowable capsule and filled with liquid through a thin delivery catheter, which is then detached. It remains in the stomach for four months, after which it automatically empties and is excreted naturally through the patient’s gastrointestinal tract.
All these therapies will enable us to have more options for our patients.
Studies have shown that intragastric balloon systems are an effective means of weight loss in patients suffering from obesity with BMIs 30 to 40kg/m2 compared to diet/exercise management alone (2–3 times better weight loss). Risk factors/limitations of the device include poor weight loss in up to 25 percent of the patients, nausea and vomiting in 60 to 90 percent, intolerance requiring early removal in 7.5 percent, and ulcers in 2 to 10 percent. Balloons are an effective and welcomed addition to the bariatric surgeon’s armamentarium for obesity treatment.
1. Benjamin SB, Maher KA, Cattau EL Jr, et al. Double-blind controlled trial of the Garren-Edwards gastric bubble: an adjunctive treatment for exogenous obesity. Gastroenterology. 1988;95(3):581–588.
2. Ulicny KS Jr, Goldberg SJ, Harper WJ, et al. Surgical complications of the Garren-Edwards Gastric Bubble. Surg Gynecol Obstet. 1988;166:535–540.
3. Genco A, Bruni T, Doldi SB, et al. Bioenteric intragastric balloon: the Italian experience with 2515 patients. Obes Surg. 2005;15:1161–1164.
4. Sallet JA, Marchesini JB, Paiva DS, et al. Brazilian multicenter study of the intragastric balloon. Obes Surg 2004;14:991-98.
5. Lopez-Nava G, Rubio MA, Prados S, et al. Bioenterics intragastric balloon (BIB®). Single ambulatory center Spanish experience with 714 consecutive patients treated with one or two consecutive balloons. Obes Surg. 2011;21:5–9.
6. Imaz I, Martínez-Cervell C, García-Alvarez EE, et al. Safety and effectiveness of the intragastric balloon for obesity. A meta-analysis. Obes Surg. 2008;18:841–846.
7. Ponce J, Quebbeman BB, Patterson EJ. Prospective, randomized, multicenter study evaluating safety and efficacy of intragastric dual-balloon in obesity. Surg Obes Relat Dis. 2012;9: 290–295.
8. Ponce J, Woodman G, Swain J, et al. The REDUCE pivotal trial: a prospective randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity. Surg Obes Relat Dis. 2015;11:874–881.
9. Abu Dayyeh, BK, Kumar, N, Edmundowicz SA, et al. ASGE Bariatric Endoscopy Task Force systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting endoscopic bariatric therapies. Gastrointest Endosc. 2015;82:425–438.
10. Lopez-Nava G, Bautista-Castaño I, Jimenez-Baños A, et al. Dual intragastric balloon: single ambulatory center spanish experience with 60 patients in endoscopic weight loss management. Obes Surg. 2015;25:2263–2267.)
11. Orbera™ Intragastric Balloon System FDA Summary of Safety and Effectiveness Data: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140008b.pdf Accessed November 28, 2015
12. ORBERA™ Intragastric Balloon System. Directions for Use (DFU). August 2015. www.orbera.com/dfu. Accessed November 28, 2015
13. Ponce J, Nguyen NT, Hutter M, Sudan R, Morton JM. Estimation of Bariatric Surgery procedures in the United States 2011–2014. American Society for Metabolic and Bariatric Surgery Brief Communication. Surg Obes Relat Dis. 2015; in press.
14. Obalon Safety Information. http://www.obalon.com/safety-information/. Accessed February 12, 2015
15. Allurion Technologies’ Elipse™ Gastric Balloon Receives European Marketing Approval. http://www.marketwired.com/press-release/-2080164.htm. Accessed February 12, 2015