The Intersection of Neuromodulation & Personalized Medicine

The field of neuromodulation has evolved through a variety of methodologies over several decades to treat various chronic conditions. According to the National Institutes of Health (NIH), its roots can be traced back to the 1930s, when clinicians began using electrodes to explore brain function for ablative therapy associated with the treatment of epilepsy.

In 1968, the first surgical spinal cord stimulator was made commercially available to treat chronic pain through electrical stimulation of the spinal cord. Other common neuromodulation modalities include stimulation of the peripheral nerves and sacral nerves – those that are responsible for the feeling of and controlling of urine and stool.

Despite its longevity and versatility, the use of neuromodulation has been somewhat lacking due to its traditional invasive nature and site-of-care requirements, says Jill Schiaparelli, MBA, chief executive officer of Avation Medical, a digital healthcare and medical technology company based in Columbus, OH, that specializes in the development of digitally enabled wearable neuromodulation therapies. “Neuromodulation has been around for decades, but most of the devices out there have required a very invasive surgical implant depending on what you’re trying to treat, such as a brain implant or a spine implant,” she explains. “It is still very young in terms of what we collectively know about how it works. The net effect of that is that there are few physicians trained to conduct the surgery and few patients who are willing to have the surgery, especially for non-life-threatening conditions.”

Today, however, the science is experiencing what the NIH has described as a “renaissance” as the concept of personalized medicine continues to evolve into a significant collaborative role with neuromodulation and advancements in digital technology continues to propel its capabilities. At Avation Medical, Schiaparelli and her team of engineers and market development executives are developing a novel at-home wearable digital therapy system that she believes will modernize the delivery of neuromodulation and personalized medicine for those patients living with chronic health conditions through less invasive means that allow patients to be the driving force behind their care. The first iteration of their platform - The Vivally System – is currently seeking an FDA indication to treat the symptoms of overactive bladder (OAB) and urge urinary incontinence (UUI), a pair of conditions that affect an estimated 33 million people and 25 million adults, respectively.

While still investigational, clinical data on the Vivally System was presented to clinicians in 2022 at the American Urogynecologic Society (AUGS) Scientific Meeting after the at-home system demonstrated an 84.8 percent global responder rate and no serious adverse events at 12 weeks among 96 OAB/UUI subjects in a multi-center clinical study.

The Personal Technological Approach

Once considered primarily as a means of utilizing a patient’s specific genetic makeup to guide decisions about their treatment, personalized medicine has developed in a way in which patients are positioned to have more responsibility for their own healthcare — empowered to become more involved with their care planning process. “But there is still more to personalized medicine than that,” said Schiaparelli, who was recently named one of the Top 25 Women Leaders in Consumer Health Tech by The Healthcare Technology Report. “The MedTech industry continues to evolve what personalized medicine means to various healthcare offerings. By combining patient-centric therapy with digitally enabled behavioral support, we believe we have created a compelling, elegant solution for the treatment of OAB/UUI.”

Once available, the system will be prescribed by a physician following a brief clinical screening to ensure that the therapy is tailored to each patient, the Vivally garment is sized to be applied to either ankle before being taken home. The stimulator targets the tibial nerve, which runs up the leg to the sacral nerves that control the bladder and pelvic floor function. Electrical pulses help to block nerve signals that are not working properly and cause unwanted bladder spasms that contribute to symptoms such as urinary urgency and urinary frequency. The screening process enables the system to establish an upper and lower boundary for stimulation known as a personalized therapeutic range, which is calibrated to each individual patient’s response to electromyographical (EMG) activity detected after stimulation of the nerve. The system also features patented closed-loop control technology that uses the patient’s own physiologic response to objectively confirm activation of the tibial nerve and continuously monitor nerve recruitment. The result is a minimization of therapy variability that the company believes will lead to better clinical outcomes.

“Avation’s research and development team spent a great deal of effort to create a garment that allows precise placement of the electrodes that are needed to activate the target nerve,” Schiaparelli told MD+DI. With 30-minute treatment sessions conducted 1-2 times per week, data is collected through the system’s app, which is paired to the garment and can develop predictive algorithms for stimulation based on the patient’s symptom profile. All data is stored in a cloud for patients and their physicians to monitor so that therapy can be adjusted as needs potentially change over time.

The system also features a patented closed-loop control technology that uses the patient’s physiologic response to objectively confirm activation of the tibial nerve and continuously monitor nerve recruitment. This approach helps patients to take control and to perform their therapy when they prefer, Schiaparelli said.

“The garment allows us to have precise placement of electrodes that are needed to target that nerve,” she explained. “As the patient’s symptoms possibly change, they can do more stimulation or less. That’s the beauty of having this in the home. They’ve now got flexibility. Our clinical studies are based on 1-3 times per week for the first three months, then the patient and doctor decide based on symptoms to either maintain or decrease therapy frequency. The patient is administering their own therapies, combining them with emerging digital health tools to help deliver therapy outside the traditional walls of medical establishments. It fits effortlessly into the patient’s lifestyle.”

An initial nerve test sets a therapeutic range that enables the system to always operate within a lower and upper personalized therapeutic range. The app controls the power to the platform, the intensity of the signal, and offers behavioral support tools directly to the patients. With OAB and UUI characterized as conditions that leave patients with a lack of control over their lives, Schiaparelli said the Vivally system helps to restore a sense of normalcy.

“Unfortunately, most people are not currently being treated for their OAB and UUI,” Schiaparelli said. “All of the standard treatment options have drawbacks. Medication can be linked to side effects, dementia, and cognitive decline. Bladder wall injections can be uncomfortable and need to be repeated every six months, with side effects that include inability to urinate and having to self-catheterize. Other neuromodulation treatment options require surgery to have a pacemaker-like device implanted into the lower back or weekly visits to the doctor to have a needle electrode inserted into the ankle for therapy. Many patients try to manage their condition by going to the bathroom more frequently, or wearing a diaper, or setting an alarm overnight so that they don’t wet the bed. These are all coping behaviors that take away the normalcy of life. And the management becomes more difficult as the condition progresses.”

Ideal Candidate Patients
According to Schiaparelli, the system is appropriate for anyone living with OAB or UUI who wants treatment that does not involve surgery, needles, or drugs. “We asked ourselves, what makes for a good overactive bladder treatment — it’s not only convenient, non-invasive therapy, but also behavioral support,” she said. “We wanted to take surgery out of the equation entirely and deliver a common-sense approach.  We started with a clean slate to reimagine how to treat patients with chronic conditions like OAB.  And that’s what we’re doing.”

Additional conditions that Avation Medical intends to address next could include other lower urinary tract issues that have been proven to benefit from neuromodulation. “It’s a long list,” Schiaparelli said. “Anywhere there is a superficial peripheral nerve that is related to a chronic condition is a good candidate for this therapy. Whichever condition we address next, it will be designed to help people feel empowered. We want people who are living with chronic conditions such as OAB to regain control. We’re trying to bring back an element of humanity to our designs.”