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A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.
The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.
“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.
In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.
The research was published online in Science Advances.
Satiety Signaling in Obesity Treatment
Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.
She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.
However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.
She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.
The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.
Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.
Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.
“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”
“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”
And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”
He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”
The VIBES Approach
The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.
Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.
The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”
Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”
“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”
The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.
Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.
Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.
Testing VIBES Satiety in Swine
To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.
The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.
To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:
- No treatment (control)
- Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
- Treated with a VIBES capsule tethered via a PEG tube
After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.
Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).
In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.
The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.
Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).
“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.
The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”
“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.
The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.
Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.
No other relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.
The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.
“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.
In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.
The research was published online in Science Advances.
Satiety Signaling in Obesity Treatment
Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.
She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.
However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.
She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.
The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.
Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.
Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.
“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”
“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”
And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”
He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”
The VIBES Approach
The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.
Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.
The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”
Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”
“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”
The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.
Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.
Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.
Testing VIBES Satiety in Swine
To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.
The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.
To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:
- No treatment (control)
- Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
- Treated with a VIBES capsule tethered via a PEG tube
After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.
Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).
In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.
The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.
Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).
“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.
The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”
“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.
The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.
Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.
No other relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.
The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.
“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.
In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.
The research was published online in Science Advances.
Satiety Signaling in Obesity Treatment
Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.
She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.
However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.
She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.
The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.
Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.
Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.
“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”
“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”
And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”
He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”
The VIBES Approach
The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.
Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.
The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”
Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”
“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”
The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.
Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.
Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.
Testing VIBES Satiety in Swine
To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.
The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.
To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:
- No treatment (control)
- Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
- Treated with a VIBES capsule tethered via a PEG tube
After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.
Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).
In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.
The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.
Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).
“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.
The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”
“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.
The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.
Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.
No other relevant financial relationships were declared.
A version of this article appeared on Medscape.com.