MIT engineers designed an ingestible capsule that vibrates within the stomach, creating an illusory sense of fullness and reducing appetite. The pill could offer a minimally invasive, cost-effective way to treat obesity. Credits:Credit: Courtesy of the researchers, MIT News

MIT Engineers develop a vibrating, ingestible capsule that might help treat obesity

Swallowing the device before a meal could create a sense of fullness, tricking the brain into thinking it’s time to stop eating.

When you eat a large meal, your stomach sends signals to your brain that cause you to feel full, allowing you to realize it’s time to stop eating. These messages can also be sent by a stomach full of liquid, which is why dieters are often advised to drink a glass of water before eating.

MIT engineers have developed a new method for capitalizing on this phenomenon, employing an ingestible capsule that vibrates within the stomach. These vibrations activate the same stretch receptors that detect when the stomach is distended, giving the illusion of fullness.

The researchers discovered that giving this pill to animals 20 minutes before eating not only stimulated the release of hormones that signal satiety, but also reduced the animals’ food intake by about 40%. Scientists still have a lot to learn about the mechanisms that influence human body weight, but if further research shows that this technology can be used safely in humans, such a pill could offer a minimally invasive way to treat obesity, according to the researchers.

“For somebody who wants to lose weight or control their appetite, it could be taken before each meal,” says Shriya Srinivasan PhD ’20, a former MIT graduate student and postdoc who is now an assistant professor of bioengineering at Harvard University. “This could be really interesting in that it would provide an option that could minimize the side effects that we see with the other pharmacological treatments out there.”

Srinivasan is the lead author of the new study, which appears today in Science Advances. Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital, is the senior author of the paper.

A sense of fullness

When the stomach stretches, specialized cells known as mechanoreceptors detect it and send signals to the brain via the vagus nerve. As a result, the brain increases the production of insulin as well as other hormones like C-peptide, Pyy, and GLP-1. All of these hormones work together to aid digestion, feeling full, and stopping eating. At the same time, ghrelin, a hunger-promoting hormone, decreases.

Srinivasan became interested in controlling this process as a graduate student at MIT by artificially stretching the mechanoreceptors that line the stomach with vibration. Previous research had shown that applying vibration to a muscle can create the illusion that the muscle has stretched further than it actually has.

“I wondered if we could activate stretch receptors in the stomach by vibrating them and having them perceive that the entire stomach has been expanded, to create an illusory sense of distension that could modulate hormones and eating patterns,”

Srinivasan says.

As a postdoc at MIT’s Koch Institute for Integrative Cancer Research, Srinivasan collaborated closely with Traverso’s lab, which has pioneered many novel approaches to drug and electronic device delivery. Srinivasan, Traverso, and their colleagues created a capsule the size of a multivitamin that contains a vibrating element for this study. When the pill, which is powered by a small silver oxide battery, enters the stomach, acidic gastric fluids dissolve the capsule’s gelatinous membrane, completing the electronic circuit that activates the vibrating motor.

In an animal study, the researchers discovered that when the pill begins to vibrate, it activates mechanoreceptors, which send signals to the brain via vagus nerve stimulation. The researchers monitored hormone levels while the device was vibrating and discovered that they mirrored hormone release patterns seen after a meal, even when the animals had fasted.

The researchers then examined how this stimulation affected the animals’ appetites. They discovered that when the pill was activated for about 20 minutes before the animals were given food, they consumed 40% less on average than when it was not activated. The animals also gained weight at a slower rate when they were given the vibrating pill.

“The behavioral change is profound, and that’s using the endogenous system rather than any exogenous therapeutic. We have the potential to overcome some of the challenges and costs associated with delivery of biologic drugs by modulating the enteric nervous system,”

Traverso says.

The current version of the pill is designed to vibrate for about 30 minutes after arriving in the stomach, but the researchers plan to explore the possibility of adapting it to remain in the stomach for longer periods of time, where it could be turned on and off wirelessly as needed. In the animal studies, the pills passed through the digestive tract within four or five days.

The study also found that the animals did not show any signs of obstruction, perforation, or other negative impacts while the pill was in their digestive tract.

An alternative approach

According to the researchers, this type of pill could provide an alternative to current approaches to treating obesity. Nonmedical interventions such as diet and exercise are not always effective, and many existing medical interventions are quite invasive. Gastric bypass surgery and gastric balloons, which are no longer widely used in the United States due to safety concerns, are examples.

Drugs such as GLP-1 agonists can also help with weight loss, but the majority of them must be injected and are therefore out of reach for many people. According to Srinivasan, the MIT capsules could be produced at a low enough cost that they would be accessible to people who do not have access to more expensive treatment options.

“For a lot of populations, some of the more effective therapies for obesity are very costly. At scale, our device could be manufactured at a pretty cost-effective price point,” she says. “I’d love to see how this would transform care and therapy for people in global health settings who may not have access to some of the more sophisticated or expensive options that are available today.”

The researchers now plan to explore ways to scale up the manufacturing of the capsules, which could enable clinical trials in humans. Such studies would be important to learn more about the devices’ safety, as well as determine the best time to swallow the capsule before to a meal and how often it would need to be administered.

Other authors of the paper include Amro Alshareef, Alexandria Hwang, Ceara Byrne, Johannes Kuosmann, Keiko Ishida, Joshua Jenkins, Sabrina Liu, Wiam Abdalla Mohammed Madani, Alison Hayward, and Niora Fabian.

The research was funded by the National Institutes of Health, Novo Nordisk, the Department of Mechanical Engineering at MIT, a Schmidt Science Fellowship, and the National Science Foundation.