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Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.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.