From the electro-compressor to Truvaga
The history of vagus nerve stimulation is a fascinating story that goes back nearly a hundred and fifty years. In the 1880s, John Leonard Corning invented the “electro-compressor” to active the vagus nerve. He was trying to treat a painful and irregular heart rhythm called super ventricular tachycardia, or SVT. Corning suspected that SVTs were the result of a vagus nerve problem rather than a circulation issue, even though a deep carotid massage was often successful in treating the problem. A deep carotid massage is a technique that is hundreds, if not thousands of years old, and involves digging the thumb into the neck of a patient to press down on and rub the carotid artery. It was used to treat SVTs, epilepsy, and a few other conditions. Corning suspected that, since the vagus nerve ran in the same sheath as the carotid, maybe it was the vagus nerve that needed to be activated. Still, his invention was designed to do both, provide electricity and press down on the carotids.
Pretty brilliant stuff, even though the electrical engineering knowhow from the 1880s left a lot to be desired, and the electro-compressor wasn’t practical or effective. Still, Corning was the first to put the ideas of vagus nerve stimulation and electrical activation of nerves together. However, if you consider techniques that include deep breathing (Prana breathing) taught by Ayurvedic medicine practitioners, herbal medicines used by the Ancient Egyptian healers, and acupuncture techniques developed in Ancient China, all of which are designed to drive parasympathetic activity over the sympathetic, humans have been using vagus nerve stimulation for a few thousand years!
The modern iterations of VNS include electrical, optical, chemical, and even mechanical stimulation devices all designed to activate the parasympathetic arm of the autonomic nervous system. Cyberonics, the company that first commercialized a VNS device, developed an implant that required a surgical placement of a palm-sized metal signal generator in the chest with an electrical lead that needed to be wrapped around the vagus nerve. How that is accomplished is a bit cringeworthy – the physician has to do a “cut down” to the carotid sheath and expose that all-important artery to get to the vagus nerve that is wrapped around it. The nerve has to then be gently lifted off the carotid artery and have a helical lead wrapped around it. Within about a week after surgery, the lead is never coming out as scar formation creates a fusion of lead, nerve, and artery that would be in serious jeopardy during any attempt to remove it. On multiple fronts, it is a fortunate thing that the technology has evolved since then to offer non-invasive ways to access the same benefits.
Besides avoiding the carotid sheath “cut down”, newer technologies have been developed that aren’t programmed to be on for 30 seconds to 2 minutes every 5 minutes for the rest of your life. You see, the original development of the implanted devices began with animal studies in which dogs were poisoned with strychnine (being a dog person, this part of the story makes me a bit sad). While dying, the dogs went through periods of continuously seizing (which was the prevailing model of epilepsy at the time). As barbaric as it sounds, in that model, the use of vagus nerve stimulation was able to stop the seizure, which is pretty amazing. The researchers were intrigued to find that the animals didn’t have the seizures recur until about 5 minutes after the stimulation was turned off, and that turning it back on every 5 minutes kept the seizure suppressed at least until the animal expired. Thus, the stimulation every 5 minutes treatment program was born. On a scientific level, the results were actually quite remarkable, but the engineer in me couldn’t help but ask whether a duty cycle on every 5 minutes was really required.
To my way of thinking, lethally poisoning a dog isn’t only tragic, it also is not equivalent to naturally occurring epilepsy. Maybe in actual epilepsy, I thought, the stimulation could be less frequent, like once per hour, or even once every eight hours. Unfortunately, neither the FDA nor the company chose to investigate whether the therapy needed to be on every 5 minutes. Still, when I asked people who had been a part of the original development program, I found that they certainly had multiple reasons to believe that the therapy could be just as effective with a duty cycle that was less frequent. For example, the implanted devices they market can be turned off with a small magnetic switch waved over the generator under the skin in the chest (where and how the lead is implanted around the vagus nerve can often leave patients with an audible change in voice, e.g., hoarseness, when the stimulation is on). Patients often did just that when they were to give talks or to sleep. Knowing this, I asked whether seizures were more frequent when the devices were turned off for an hour or so. The answer, I found out, was no!
So, I pressed a bit further and asked whether any clinical studies had ever been conducted in which the active treatment, which is a 30Hz signal (on for one millisecond and then off for 32 milliseconds, repeatedly), was set to provide its 30-second to 2-minute doses less frequently. The answer I got was a bit of a surprise; it was “yes”. In a pilot study to demonstrate safety, they had implanted devices into patients with epilepsy but programmed the therapy to turn on only once per hour. Immediately intrigued, I asked what the clinical results had been. The answer I received shocked me. “It worked great,” was the reply. “So why did you go back to stimulating every hour,” I asked. I was told that the therapy was super safe, and that the developers had been happy to know that the device didn’t need to be on constantly, but that they were happy with every 5 minutes for several reasons. The first was that they figured more therapy would be better. Second, the fact that the animal studies had been safe and effective at every 5 minutes, they figured FDA and the market would accept it. The third reason was that they figured it would be an easier sell to patients to have a surgery if the therapy needed to be delivered every 5 minutes versus only once per hour. Finally, the model the company was selling would require a battery change every 5 to 7 years if it was on every 5 minutes, versus closer to 12 to 15 years if it was only used once per hour. Frankly, that last reason didn’t sit well with me … and the one before it smelled a little fishy, as well.
The good news for us was, we had a really good idea (actually several) about how to deliver the therapy to nearly the same spot on the vagus nerve (the neck) from the outside. There were some other people trying to stimulate another nerve, called the tragus nerve, which merges with the vagus nerve, but sits around the ear and contains only one hundredth of the nerve fibers of the full vagus in the neck. Worse yet, unlike the rest of the vagus nerve, which enters right up into the brainstem to deliver the signal, the tragus nerve fibers only enter that area indirectly by passing through the lateral trigeminal islands (an area peripheral to where the main vagus nerve goes), so there was some concern that the effects wouldn’t be as powerful or provide the same benefits.
Of course, measuring the benefits of our non-invasive vagus nerve stimulation had to come second to ensuring that the technology was safe. There were even a few skeptics who weren’t convinced that our technology could even get to the vagus nerve. After eight different pre-clinical programs, including: electric field modeling; functional MRI studies; recording electro encephalograms; observing neurotransmitter system responses; measuring circulating cytokine levels; countless comparisons to implanted stimulator effects in asthma, stroke, and headache; and even studying pupil responses to stimulation, we were pretty much able to put that questions to rest (other than people who were just trying to not believe because they were making implanted devices that non-invasive treatment was about to make obsolete). The founder and former CEO of the company that pioneered implanted vagus nerve stimulation for epilepsy (who joined our Board of Directors until his retirement) was far more fair-minded when he commented, “congratulations, we always knew that someday VNS would be delivered non-invasively, but we had no idea how to do it.”
So, having confirmed that our technology could activate the right fibers in the vagus nerve, we needed to ensure that it didn’t trigger any negative side effects. That process was not so difficult because the animal studies and physiological modeling efforts we had already completed showed us that the difference in energy levels necessary to activate the A fibers we wanted to stimulate and the C fibers that are associated with the potential negative side effects was a factor of 15. By comparison, when engineers build bridges, roads, and dams, they typically use safety factors of 2 or 3, and airplanes and cars have safety factors that are closer to 1.1 or 1.2. A safety factor of 15 let us cap the maximum power output from the device, thus making it impossible, not just unlikely, that our non-invasive technology could do anything to hurt someone. Even the FDA, when they evaluated it for the treatment of Cluster Headaches, said that the risks were, “mild, transient, and inherently self-limiting.” Basically, that last part meant that if there was any problem, the patient could just pull the device away from contact with the skin, stopping the therapy instantly.
Tens of thousands of people have used literally millions of treatments, for the treatment of everything from stress and wanting a better night sleep, to stopping suicide headaches and relieving CoVID breathing challenges, and it is even being used in patients who just suffered acute strokes. The safety profile of the therapy delivered with Truvaga is amazing, and the number one comment that we hear in the letters we receive back from customers is, “you gave me my life back.” I’m pretty sure that is the device wasn’t safe and easy to use, we’d be hearing a lot of complaints, and we hear none about how it feels, or how it works.
As the saying goes, “haters gonna hate,” and there are people and companies out there who are looking to tear down nVNS because they have something else to sell. Don’t be misled. Truvaga is not just safe and easy to use. It is comfortable and it works. It takes 4 minutes per day (2 minutes in the morning and 2 minutes in the evening) and it provides the sort of benefit that usually takes an hour of meditation, an hour massage, or even an hour of yoga to achieve. I’m not suggesting for a second that you stop doing those things if you have the time, but I am suggesting that you try Truvaga. You might just be the next person to say, “thank you for giving me my life back.”