Brigham researchers develop an implantable device to detect and respond to opioid overdose
In preclinical models, the subcutaneously implanted device continuously monitored vital signs and delivered naloxone automatically and rapidly when it detected opioid overdose.
Brigham and Women's Hospital
In preclinical models, the subcutaneously implanted device continuously monitored vital signs and delivered naloxone automatically and rapidly when it detected opioid overdose
The opioid epidemic continues to have devastating effects in the United States, exacerbated by the increasing presence of fentanyl in illicit opioids. Naloxone is an effective antidote, but it usually requires rapid administration from a bystander. Now, researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, and MIT, have developed an implantable device to detect and reverse opioid overdoses. The device, which they call “iSOS,” continuously monitors heart and respiratory systems for signs of overdose and automatically delivers naloxone when necessary. In preclinical studies, iSOS effectively detected and reversed opioid overdoses. The study is published in the journal Device.
“Naloxone is life-saving but frequently may not be delivered in time,” said co-first author Peter Ray Chai, MD, MS, Department of Emergency Medicine at Brigham and Women's Hospital. “The iSOS device provides a highly innovative strategy to provide detection of opioid overdose, allowing for precise administration of naloxone at the moment it is needed, hopefully saving individuals from overdose and facilitating continued recovery from opioid use disorder.”
During overdoses, people generally lose consciousness, so having an automated delivery system for naloxone could save the lives of people who use opioids by themselves.
“In overdose cases where there is a bystander nearby, that individual can be rescued through either intramuscular or intranasal administration of naloxone, but you need that bystander. We wanted to find a way for this to be done in an autonomous fashion.” said corresponding author Giovanni Traverso, MB, PhD, MBBCH, Department of Medicine at Brigham and Women’s Hospital and MIT.
To do away with the need for bystander intervention, the researchers wanted to design a “closed loop” system that could both detect opioid overdose and deliver the drug without outside guidance. To enable autonomous detection, the team fitted the device with multiple sensors that continuously monitor the user’s respiratory rate, heart rate, body temperature, and blood oxygen saturation. These sensors connect to an algorithm that is trained to recognize the signs of overdose by integrating the various cardiorespiratory signals.
When the device detects a suspected opioid overdose, it begins buzzing to alert the user and sends an alert to their phone which allows the user to cancel naloxone administration if they are not experiencing an overdose. If it is not overridden, the device administers a shot of naloxone directly into the user’s tissue.
“Beyond the closed loop, the device can also serve as an early detection or warning system that can help alert others—whether it be loved ones, healthcare professionals or emergency services—to the side of the person so that they can help intervene as well,” said Traverso.
“To combat the high mortality associated with opioid overdoses, our fully implantable iSOS—with its continuous monitoring and rapid drug infusion capabilities—could serve as a pivotal next-generation antidote platform,” said co-first author Seungho Lee, PhD, a research scientist at MIT and in the Department of Medicine at Brigham and Women's Hospital.
The prototype device measures 8 mm x 12 mm x 78 mm (larger than a contraceptive implant but smaller than a subcutaneous cardiac defibrillator). It has a wirelessly rechargeable battery that can last up to 14 days, a refillable drug reservoir, and can be implanted subcutaneously via a minimally invasive procedure under local anesthesia. The team tested the device’s safety and efficacy in a large animal model, finding that the device effectively detected and reversed opioid overdoses in 24 out of 25 pigs.
The researchers note that the device could be particularly useful for individuals who have previously overdosed, since these individuals are more likely to overdose again. They also say that having an implantable device may be more effective than a wearable device.
“The problem with wearables is that one has to wear them, and that in itself presents a potential challenge from an adherence perspective,” says Traverso. “If the patient really wants to help protect themselves against overdose, an implantable or ingestible device could help support this sort of general vision.”
The researchers are now working to further optimize and miniaturize the device and intend to conduct additional preclinical trials before moving onto human testing. They also plan to begin collecting data on end-user preferences to help guide their engineering efforts.
“Understanding the preferences of this patient population will be a critical part of our ongoing work to develop and mature this technology, said Traverso. “This is only the first lab-based prototype, but even at this stage we’re seeing that this device has a lot of potential to help protect high-risk populations from what otherwise could be a lethal overdose.”
Authorship: In addition to Traverso Chai, and Lee, BWH authors include co-first author Hen-Wei Huang, Tom Kerssemakers, Ali Imani, Jack Chen, Marco Heim, Jessica Y. Bo, Adam Wentworth, Fokion T. Sanoudos–Dramaliotis, Ian Ballinger, Alexander Alexiev, Jason Li, and Siheng Sean You.
Additional authors include Saurav Maji, Matt Murphy, Gloria H Kang, Niora Fabian, Josh Jenkins, Andrew Pettinari, Keiko Ishida, Alison M. Hayward, and Anantha Chandrakasan.
Disclosures: The authors declare submission of a provisional patent application (PCT/US2022/080385) describing the materials and applications of the systems described here. Complete details of all relationships for profit and not for profit for Traverso can be found at the following link. All other authors declare that they have no competing interests. Work described in this manuscript was funded by Novo Nordisk, the McGraw Family Funding, MIT Department of Mechanical Engineering, MIT Karl Van Tassel (1925) Career Development Professorship Chair. Chai funded by NIH DP2DA056107.
Funding: Novo Nordisk, The McGraw Family Foundation, MIT Department of Mechanical Engineering, MIT Karl Van Tassel (1925) Career Development Professorship Chair.
Paper cited: Huang, H et al. “An Implantable System for Opioid Safety (iSOS)” Device DOI: 10.1016/j.device.2024.100517
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About Mass General Brigham
Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.
Journal
Device
Method of Research
Observational study
Subject of Research
Animals
Article Title
An Implantable System for Opioid Safety (iSOS)
Article Publication Date
14-Aug-2024
COI Statement
The authors declare submission of a provisional patent application (PCT/US2022/080385) describing the materials and applications of the systems described here. Complete details of all relationships for profit and not for profit for Traverso can be found at the following link. All other authors declare that they have no competing interests. Work described in this manuscript was funded by Novo Nordisk, the McGraw Family Funding, MIT Department of Mechanical Engineering, MIT Karl Van Tassel (1925) Career Development Professorship Chair. Chai funded by NIH DP2DA056107.
An implantable sensor could reverse opioid overdoses
The new device, which can be implanted under the skin, rapidly releases naloxone when an overdose is detected
Massachusetts Institute of Technology
In 2023, more than 100,000 Americans died from opioid overdoses. The most effective way to save someone who has overdosed is to administer a drug called naloxone, but a first responder or bystander can’t always reach the person who has overdosed in time.
Researchers at MIT and Brigham and Women’s Hospital have developed a new device that they hope will help to eliminate those delays and potentially save the lives of people who overdose. The device, about the size of a stick of gum, can be implanted under the skin, where it monitors heart rate, breathing rate, and other vital signs. When it determines that an overdose has occurred, it rapidly pumps out a dose of naloxone.
In a study appearing in the journal Device, the researchers showed that the device can successfully reverse overdoses in animals. With further development, the researchers envision that this approach could provide a new option for helping to prevent overdose deaths in high-risk populations, such as people who have already survived an overdose.
“This could really address a significant unmet need in the population that suffers from substance abuse and opiate dependency to help mitigate overdoses, with the initial focus on the high-risk population,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.
The paper’s lead authors are Hen-Wei Huang, a former MIT visiting scientist and currently an assistant professor of electrical and electronic engineering at Nanyang Technological University in Singapore; Peter Chai, an associate professor of emergency medicine physician at Brigham and Women’s Hospital; SeungHo Lee, a research scientist at MIT’s Koch Institute for Integrative Cancer Research; Tom Kerssemakers and Ali Imani, former master’s students at Brigham and Women’s Hospital; and Jack Chen, a doctoral student in mechanical engineering at MIT.
An implantable device
Naloxone is an opioid antagonist, meaning that it can bind to opioid receptors and block the effects of other opioids, including heroin and fentanyl. The drug, which is given by injection or as a nasal spray, can restore normal breathing within just a few minutes of being administered.
However, many people are alone when they overdose, and may not receive assistance in time to save their lives. Additionally, with a new wave of synthetic, more potent opioids sweeping the U.S., opioid overdoses can be more rapid in onset and unpredictable. To try to overcome that, some researchers are developing wearable devices that could detect an overdose and administer naloxone, but none of those have yet proven successful. The MIT/BWH team set out to design an implantable device that would be less bulky, provide direct injection of naloxone into the subcutaneous tissue, and eliminate the need for the patient to remember to wear it.
The device that the researchers came up with includes sensors that can detect heart rate, breathing rate, blood pressure, and oxygen saturation. In an animal study, the researchers used the sensors to measure all of these signals and determine exactly how they change during an overdose of fentanyl. This resulted in a unique algorithm that increases the sensitivity of the device to accurately detect opioid overdose and distinguish it from other conditions where breathing is decreased, such as sleep apnea.
This study showed that fentanyl first leads to a drop in heart rate, followed quickly by a slowdown of breathing. By measuring how these signals changed, the researchers were able to calculate the point at which naloxone administration should be triggered.
“The most challenging aspect of developing an engineering solution to prevent overdose mortality is simultaneously addressing patient adherence and willingness to adopt new technology, combating stigma, minimizing false positive detections, and ensuring the rapid delivery of antidotes,” says Huang. “Our proposed solution tackles these unmet needs by developing a miniaturized robotic implant equipped with multisensing modalities, continuous monitoring capabilities, on-board decision making, and an innovative micropumping mechanism.”
The device also includes a small reservoir that can carry up to 10 milligrams of naloxone. When an overdose is detected, it triggers a pump that ejects the naloxone, which is released within about 10 seconds.
In their animal studies, the researchers found that this drug administration could reverse the effects of an overdose 96 percent of the time.
“We created a closed-loop system that can sense the onset of the opiate overdose and then release the antidote, and then you see that recovery,” Traverso says.
Preventing overdoses
The researchers envision that this technology could be used to help people who are at the highest risk of overdose, beginning with people who have had a previous overdose. They now plan to investigate how to make the device as user-friendly as possible, studying factors such as the optimal location for implantation.
“A key pillar of addressing the opioid epidemic is providing naloxone to individuals at key moments of risk. Our vision for this device is for it to integrate into the cascade of harm-reduction strategies to efficiently and safely deliver naloxone, preventing death from opioid overdose and providing the opportunity to support individuals with opioid use disorder,” says Chai.
The researchers hope to be able to test the device in humans within the next three to five years. They are now working on miniaturizing the device further and optimizing the on-board battery, which currently can provide power for about two weeks.
The research was funded by Novo Nordisk, the McGraw Family Foundation at Brigham and Women’s Hospital, and the MIT Department of Mechanical Engineering.
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Written by Anne Trafton, MIT News
Journal
Device
Article Title
"An Implantable System for Opioid Safety (iSOS)"
Implantable device detects opioid overdose and automatically administers naloxone in animal trials
Cell Press
image:
Naloxone deliver device
view moreCredit: Hen-Wei Huang
Naloxone is an effective treatment for opioid overdose, but it usually requires a bystander to step in and administer it. Now, researchers have developed an implantable device that can independently detect overdose and automatically administer naloxone. The device, which the researchers call “iSOS,” includes multiple sensors that allow it to continuously monitor the user’s heart and respiratory systems and a pump that rapidly administers naloxone when needed. It’s yet to be tested in humans, but in animal trials, iSOS successfully revived 24 out of 25 overdosed pigs within 3.2 minutes. The study is published August 14 in the journal Device.
“Having an automated robotic system that is able to sense and reverse opiate overdose could be transformational, particularly for high-risk populations,” says senior author Giovanni Traverso (@cgtraverso), a clinician and biomedical engineer at MIT, Brigham and Women’s Hospital, and the Broad Institute. “Substance use is a fundamental disorder, and individuals who have had overdoses are at higher risk of overdosing again. To help support this population and those at the greatest risk of overdosing, we wanted to develop an automated way of providing early detection of those events, and then couple that signal with the quick release of naloxone.”
Opioid overdose from both prescription and illicit drugs can cause permanent brain damage within 3 minutes and death within 4 to 6 minutes, so rapid administration of naloxone is critical. However, because opioid use often results in a loss of consciousness, self-administration of naloxone is not usually an option, and bystanders need to be able to recognize the symptoms and respond quickly.
“The most challenging aspects of developing an engineering solution to prevent overdose mortality are addressing patient adherence and willingness to adopt new technology, minimizing false positive detections, and ensuring the rapid delivery of antidotes,” says co-first author and roboticist Hen-Wei Huang of Brigham and Women’s Hospital, Harvard Medical School, and Massachusetts Institute of Technology. “Our proposed solution tackles these unmet needs by developing a miniaturized robotic implant equipped with multi-sensing modalities, continuous monitoring capabilities, on-board decision-making, and an innovative micro-pumping mechanism.”
The team engineered a subcutaneously implantable device with multiple sensors that allow it to continuously monitor the user’s respiratory rate, heart rate, body temperature, and blood oxygen saturation. These sensors are connected to a decision-making algorithm that integrates the various vital signs to decide whether an overdose is occurring.
The device contains a refillable drug reservoir and an active pump that can quickly release a jet of naloxone directly into the user’s muscle if an overdose is detected. When it detects a suspected overdose event, the device begins buzzing and simultaneously sends an alert to the user's smartphone that allows them to override the decision for naloxone administration in case they are not actually experiencing an overdose. Though the system is designed to be a “closed loop”—meaning it both detects and delivers the drug—it also incorporates an alarm system that could alert loved ones or health care workers to the user’s side.
In preliminary tests in pigs, the device proved effective at detecting and reversing opioid overdose. Going forward, the researchers plan to continue to optimize and miniaturize the device, which currently measures 8 mm x 12 mm x 78 mm (approximately 0.3 x 0.5 x 3 inches).
“This is only the first generation of this device, and so there's certainly room for further miniaturization and more testing in large mammals like pigs, but we’re looking to begin testing in humans in the next few years,” says Traverso.
The team also plans to begin researching and collecting data on the preferences of the people who would actually be using the device.
“Understanding the end-user preference and acceptability is a critical element,” says Traverso. “Part of our future work will be to really inform the general perception and acceptability of this type of device, which will help inform some of the engineering as we continue to develop this technology.”
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This research was supported by Novo Nordisk, the McGraw Family Foundation, Brigham and Women’s Hospital, and MIT.
Device, Huang et al., “An implantable system for opioid safety (iSOS)” https://www.cell.com/device/fulltext/S2666-9986(24)00417-4
Device (@Device_CP) is a physical science journal from Cell Press along with Chem, Joule, and Matter. Device aims to be the breakthrough journal to support device- and application-oriented research from all disciplines, including applied physics, applied materials, nanotechnology, robotics, energy research, chemistry, and biotechnology, under a single title that focuses on the integration of these diverse disciplines in the creation of the cutting-edge technology of tomorrow. Visit https://www.cell.com/device/home. To receive Cell Press media alerts, contact press@cell.com.
Journal
Device
Method of Research
Experimental study
Subject of Research
Animals
Article Title
An Implantable System for Opioid Safety (iSOS)
Article Publication Date
14-Aug-2024
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