Revolutionizing Neuropathic Symptom Relief with Scrambler Technology

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics Program and Co-Director of the Cleveland Clinic Sarcoma Program. Today I'm very happy to be joined by Dr. Renato Samala and Dr. Chirag Patel. They're both palliative medicine physicians here at Cleveland Clinic and they are here today to talk to us about treating neuropathic symptoms with scrambler technology. So welcome gentlemen.

Chirag Patel, MD: Thanks for having us.

Renato Samala, MD: It's a pleasure to be here.

Dale Shepard, MD, PhD: Let's get an overview about what you do here at the Cleveland Clinic, your palliative medicine physicians. Renato, let's start with you.

Renato Samala, MD: So, I practice palliative care both in the hospital at main campus and also see patients in clinic at the cancer center.

Dale Shepard, MD, PhD: Okay, very good. Chirag?

Chirag Patel, MD: Yeah, I do the same thing as Renato pretty much. We're mostly outpatient, we also do inpatient work, seeing patients at the cancer center. I think I'd add just for clarification that we help out with all different types of patient's symptoms related to cancer and cancer treatments, just to give a scope of what the palliative medicine service is here.

Dale Shepard, MD, PhD: Okay, very good. And then I guess even just to take a step back, so palliative medicine... we've had some episodes and we've talked a little bit about palliative medicine... but just give us a really brief overview from a palliative medicine standpoint, how does that work in terms of the team approach to medicine and working with the rest of the team?

Renato Samala, MD: So with palliative medicine, which the umbrella term is palliative care, but the medical part is palliative medicine, we get involved in the care of patients living with any type of serious illness. So cancer is definitely at the top of the list. But I myself, I also see patients with advanced Parkinson's disease, that's my side hustle, and a few of my colleagues also see patients with say, heart failure, COPD, et cetera. And we help the main team take care of patients in the sense that we help take care of symptoms, whether it's from the disease itself or from the treatment. And then we also help with what we call advanced care planning, putting resources in place, making tough decisions as they go on with the illness.

Dale Shepard, MD, PhD: Excellent. So we're going to talk about a couple of things big picture. There's this thing called scrambler technology and we're going to talk about neuropathic symptoms. So let's start with the neuropathic symptoms part. So Chirag, give us a little bit of an idea, what are we talking about with neuropathic symptoms and how do people get them?

Chirag Patel, MD: So in the context of our practice, which is largely cancer-based, a lot of patients who undergo cancer treatments end up with different neuropathic symptoms, whether it be neuropathic pain or numbness or tingling caused by just disruption of the nervous system, the peripheral nervous system specifically. So the different chemotherapeutics can cause this, radiation therapy can cause this more locally or focally, different procedures, surgeries, things like that can damage the nervous system as well. And sometimes it heals up, sometimes it heals up just a little bit but not completely, and sometimes it doesn't really heal up all that much. And so patients can be left with sometimes lifelong pain, numbness, tingling. Those are all the neuropathic symptoms that we think about.

Dale Shepard, MD, PhD: So the disease and the treatment can significantly cause a worsening quality of life as a result.

Chirag Patel, MD: Exactly, yeah. So patients then are dealing with the chronic symptoms of maybe the pain or maybe they're having difficulty getting around because of the numbness in their feet or just can't get comfortable at nighttime to go to sleep because of the tingling that's occurring.

Dale Shepard, MD, PhD: So Renato, give us an idea, if we think about these peripheral neuropathies and these neuropathic symptoms, what are kind of the traditional ways that we've treated them?

Renato Samala, MD: So say I get a patient in clinic referred to me for treatment of neuropathic pain or neuropathic symptoms, one of the first interventions that would come to mind would be medications or drugs. And the more commonly prescribed ones include gabapentin or Neurontin. Patients might also be prescribed Lyrica or pregabalin. And another one that's commonly out there is Cymbalta or duloxetine. And opioids as well. So medications are, as far as we are concerned, the foremost alternative for treating neuropathic symptoms.

Dale Shepard, MD, PhD: And I guess when we start those medical therapies, so Chirag, how successful are these typically?

Chirag Patel, MD: Unfortunately, our medications aren't all that great. They work in a minority of patients. And so we're left with a lot of trial and error, essentially cycling through various medication options in hopes that one of them sticks as in has a good benefit, has minimal side effects, but even when one does have a good benefit we have to balance out a lot of side effects with the medications. And so trying to figure out what can we do that is not medication-based for these neuropathic symptoms is really important for us.

Dale Shepard, MD, PhD: Do we tend to have better success from a medication standpoint using medications to treat for neuropathy that is based on treatments patients have received versus the disease or does it matter?

Chirag Patel, MD: I'd say many of our studies about treatment-related complications, treatment-related neuropathies, the medications that we use are actually just borrowed from other types of neuropathies. So we actually don't have a great understanding of how these medicines work for say, chemotherapy-induced neuropathy. And the studies that we do have aren't all that encouraging. So you can't really differentiate too much about whether they work better with chemotherapy versus not chemotherapy-related issues. But I'll say that our knowledge base is largely based on non-chemotherapy neuropathies.

Dale Shepard, MD, PhD: Got it.

Renato Samala, MD: And based on what I've seen in my practice, I seem to have better luck treating neuropathy caused by agents like chemotherapy drugs versus those caused by, say, surgery, people who've had a part of their lungs removed or their breast removed. Those, in my experience, tend to be quite difficult to treat, quite resistant to the usual drugs that we use.

Dale Shepard, MD, PhD: Well, let's shift gears a little bit. Scrambler technology. So I somewhat naively normally sort of have this construct where I think you guys as palliative medicine docs primarily doing medical therapies, sometimes we think about pain management people doing procedural things, sort of thing. But this is more of a procedure that you guys are involved in. It's called scrambler technology. So give us a little bit of an idea what this is all about.

Renato Samala, MD: Sure. So I got into it because it's an opportunity to help patients, to treat my patients without prescribing them a pill. So it's a procedure, it's a non-invasive procedure, and the way it's creator, Giuseppe Marinaro, who's a biophysicist from Rome, Italy described it is, it's an FDA approved electro-analgesic device that's used for the treatment of refractory neuropathic symptoms. I threw in a lot of big words there, but for our listeners, let me break it down. So it uses electricity, small currents of electricity that passes through electrodes. So if a patient's getting treated, the way I describe the procedure is imagine you're getting an EKG done, so you're going to have electrodes stuck on specific parts of your body as if you're getting an electrocardiogram done. And it's FDA approved, this was approved I believe in 2009, and it's an alternative for patients who've failed the usual medications that we use for treating neuropathic symptoms.

Dale Shepard, MD, PhD: And so how long might a session be? This is a procedure where you sort of put electrodes around the area of the pain?

Renato Samala, MD: In the literature a session has been described to last between 30 to 60 minutes. So we started doing this in November 2022 and we were able to do a small study just to look at all the patients we've treated from November 2022 to June 2023. Our mean time, our average time for treating patients, came down to 46 minutes, but typically a session would last for between 30 to 60 minutes and it goes for 10 days. It has to be 10 consecutive days with Saturday and Sunday being off. So that's a main requirement that we have for potential candidates for this treatment. They have to be able to come to clinic and get the treatment for 10 consecutive days.

Dale Shepard, MD, PhD: And Chirag, mechanistically how does this differ from something like a TENS unit, which is also kind of electrically based?

Chirag Patel, MD: So the scrambler therapy is essentially feeding you electrical signals like Renato was saying, and your body's picking up these very specific electrical signals that are meant to reprogram, retrain the brain into thinking that these painful stimuli are no longer being transmitted. See what happens in chronic neuropathic pain is that the body adapts over time and these pain signals get almost hardwired into your spinal cord and into your brain. And so trying to break a cycle of chronic pain inputs into the spinal cord is really the goal of the scrambler therapy technology. And what they do is they just replace the pain signal input with this non-painful signal input. And over the course of the 10 treatments that Renato was talking about, the brain then adapts over time, loses the memory that it creates about a pain signal and sort of gets reset, you could say, into a non-chronic pain state.

Dale Shepard, MD, PhD: So essentially you're reprogramming the nerve signals rather than, or dare I say, scrambling-

Chirag Patel, MD: Yes.

Dale Shepard, MD, PhD: ... the nerve signal rather than a TENS unit which would just block the signal. So it's more of a mechanical, if you will, block of a signal?

Chirag Patel, MD: Right, right. So a TENS unit has a different type of electrical signal and it's stimulating a different type of nerve fiber. And the nerve fiber that gets stimulated by the TENS unit is essentially trying to overwhelm the nerve fibers that the pain signals are being transmitted through. So you have a couple different nerve types and one of them is transmitting signals that the TENS is bringing up and the other one is, yeah, scrambled I guess is the best word for it, by the scramble therapy machine.

Dale Shepard, MD, PhD: How clever.

Chirag Patel, MD: Yeah, so that's where the name comes from.

Dale Shepard, MD, PhD: So if someone goes through these 10 sessions, how durable has this been proven to be? Do people sort of revert back to those sort of previously hardwired signals or what about durability?

Renato Samala, MD: That's the name of the game, I think, and there's been a lot of studies done on this. The first study came out in 2003. If you scour the literature, some of these studies, the follow-up period was a matter of weeks. The longest I've seen was about six months. Plus there are case reports and anecdotal reports. I think the jury is still out there as to this type of treatment really lasting for weeks, months, years. Based on my own experience though, by the 10th day some of the patients I treated really felt well enough that they didn't even need all 10 treatments. Whereas some of the patients I treated did not feel any difference even after 10 treatments. But generally the studies have been positive. It's just not clear yet how durable the effect is, and there have also been protocols in studies mentioned out there where people needed to be retreated.

Dale Shepard, MD, PhD: And so we started this in November of '22, have we had very many cases where we've retreated patients here at the Cleveland Clinic?

Renato Samala, MD: In my experience, I haven't retreated any of the patients that we treated here, but I've retreated two patients so far. One of them had chemotherapy induced peripheral neuropathy way back in... I think it was around 2015 or so... and then she participated in a trial at the Mayo Clinic with scrambler and then did well and then came to us for a retreatment and did well as well after 10 treatments. And then the other person, same thing, chemotherapy neuropathy, got treated in New Jersey, did fairly okay. He thought that the machine was not the greatest, it had duct tape all over it. So he came to us, got treated, after five days he was fine. He said he's fine and he's done.

Dale Shepard, MD, PhD: Excellent. So Chirag, tell us a little bit, are there particular patients... of course because of the way it's been studied patients of course have to be refractory to the medical therapies... but are there particular patients that you might think are more apt to respond in terms of type of symptom, location in the body, are there sort of people that you'd automatically say might be a good scrambler candidate?

Chirag Patel, MD: Yes. I think the main thing to realize is that the pain, while we're focusing on neuropathic pain primarily, there's reports about all sorts of different pains responding. And so the approach we've taken with this is to do sort of a test session first on a patient. So in other words, have them come in, have them sit down for just a single session, see how their pain responds. If it's enough of a response to warrant a full treatment course, the 10 sessions in a row, then we'll bring them back, scheduling them in for 10 further treatments. So sort of N of 1 trials for everyone. And that way we try and avoid patients going through a whole treatment course and finding out, hey, this didn't work all that well, or the opposite of this could have worked but we never even gave it a shot.

Dale Shepard, MD, PhD: I guess on the opposite side, Renato, there are patients that shouldn't get this therapy. Are there sort of contraindications to this?

Renato Samala, MD: Yeah, we do have a list, Dale. So based on the manufacturer of the machine's literature, we're not supposed to treat patients with implanted electronic devices. So folks with pacemakers, defibrillators, spinal cord stimulators, that's a no. And we have gotten referrals of such types of patients and we've said no to those. Other contraindications that they mentioned include patients with open wounds on parts of their body that are supposed to be treated, patients who are pregnant or nursing. For our own use, for our own scrambler team, we figured that patients who are still receiving specific medications or chemotherapeutic drugs that do cause peripheral neuropathy are not good candidates for this. Say somebody with multiple myeloma receiving bortezomib or somebody with some type of cancer receiving some platinum-based chemotherapy, it's likely not prudent to treat those folks.

Dale Shepard, MD, PhD: Are there any additional contraindications to this therapy?

Renato Samala, MD: Yeah, so patients with epilepsy, that's a major contraindication and people taking anticonvulsants, including gabapentin and pregabalin, which is why before we treat patients, even before we have them come in for that initial evaluation, they have to be off of gabapentin or pregabalin.

Dale Shepard, MD, PhD: Do you find that there's some anxiety with patients who have been sort of reliant on these medications for a long period of time and you go, okay, I got this thing that might work for you but you've got to stop what you've been doing?

Renato Samala, MD: Absolutely. I've had patients where we did the initial evaluation and they had to be off of it for a dose, like the night before, and then they did well during the evaluation. And then when we had to bring them in for the start of the actual 10-day treatment, they had to be weaned off of either gabapentin or pregabalin. And that weaning period for some patients could be difficult and certainly anxiety provoking.

Dale Shepard, MD, PhD: Yeah, it makes sense. So this has been around, you said, since 2009. Chirag, of course this is always a problem with most things we do, how about coverage? Are there issues with getting coverage for this?

Chirag Patel, MD: So we have it set up so that it's an out-of-pocket expense. The coverage is pretty spotty and very small when it does exist. And so the out-of-pocket expense for our patients ends up being about $300 a session. And so over the course of 10 sessions we're looking at about a $3,000 cost then. Some patients have a little bit shorter than the 10 sessions. Occasionally you'll have someone who needs a few more sessions than the 10 to really get the full benefit as well.

Dale Shepard, MD, PhD: Is this partly driven because it would traditionally fall under medical coverage, whereas a lot of the other medical therapies would be prescription coverage or what drives the fact that it's FDA approved and there's difficulties with coverage?

Chirag Patel, MD: I think it's the payer's determination of how much coverage they should be providing as in what the reimbursement should look like doesn't match what the reimbursement of what-

Dale Shepard, MD, PhD: Of what's actually involved with-

Chirag Patel, MD: Yeah, what would actually be involved.

Dale Shepard, MD, PhD: Gotcha, makes sense. The technology has been around for a fairly long period of time, coverage issues, how widely available is it?

Chirag Patel, MD: Before we started our scrambler therapy practice here at the clinic, I had a couple patients who were traveling across multiple states to get them. One in New Jersey, one down in Florida, and it's quite spotty that way. You can probably count the number of scrambler therapy centers in the state of Ohio on one hand. I don't know exactly what the numbers, but not very available.

Dale Shepard, MD, PhD: I guess the point then would be that if somebody's listening in and it sounds like it might be a good therapy for their patient, it might be something that would be a reasonable thing to have them referred to you guys and talk about the benefits.

Renato Samala, MD: In terms of availability, I think at this point it's mostly the large centers that have them, such as Mayo Clinic, Johns Hopkins, et cetera. Before we started scrambling patients, so to speak, we, myself, Chirag and Dr. Shoemaker, we all trained with this ex-anesthesiologist who's now focused on pain management and we had to go to his practice over in Idaho, in Boise, Idaho. I think that's part of the reason why it's not covered by insurance as much as we would like it to be yet, because it's not as mainstream as other treatment alternatives, or perhaps they're still waiting for better outcomes or clear outcomes to emerge.

Dale Shepard, MD, PhD: Makes sense. So what's next with this technology? Is it differences in the equipment itself, combinations with drugs, different things we're trying to treat? Renato, let's start with you.

Renato Samala, MD: Yeah, we've actually opened our doors for patients with other causes of neuropathic symptoms. When we started a couple of years ago, we focused on patients with chemotherapy-induced neuropathy. The last time I treated a patient, this was somebody with complex regional pain syndrome or formerly known as reflex sympathetic dystrophy, and she did marvelously well after 10 treatments. And at this point, I believe we've also been open to treating patients with chronic pain from other sources, people with diabetic neuropathy. There's a collaboration that we've started to explore with pediatric pain management. There's a specialist here at the clinic who treats particularly adolescents with chronic pain who've exhausted all sorts of treatments and I believe it's just a matter of time when we start treating those patients. And then on the research end, it would really be fascinating and interesting to see how durable the effects of this treatment is. So we're trying to come up with a protocol to follow these patients for up to a year to see how well they did.

Dale Shepard, MD, PhD: Excellent. Chirag, what would you like to see as further advances?

Chirag Patel, MD: I think the main thing that I would hope to see, if I could create my own healthcare system, would be just to give better access to the therapy itself. Right now we have between the cost constraints and the geographic constraints for many patients having to travel back and forth to our clinic on a daily basis, it's a pretty limited intervention that can be offered from a population base. So hopefully we can eventually work towards a more commonly used scrambler therapy program.

Dale Shepard, MD, PhD: That's great. I mean clearly this is a significant problem. I've had patients in the past who are on observation well past their chemo and they have no cancer but they have significant quality of life problems because of neuropathy. So the work you guys are doing with this is fantastic.

Chirag Patel, MD: Thank you. I'm glad that we're able to put out a product that seems to be helpful and doesn't have any side effects to think of really.

Dale Shepard, MD, PhD: Yeah, fantastic.

Renato Samala, MD: And to Chirag's point, just to give you an idea, the machine itself, it kind of looks like... I always tell folks that it looks like either a guitar amplifier, like the big ones, or an old school VCR player. So imagine a big box with five pairs of electrical leads coming out of it. So maybe someday this can be much more portable, it might take the size of a TENS unit and people can just do this intervention themselves. So that might be something to look forward to hopefully in the near future. But access would be up there as well in terms of things to look forward to.

Dale Shepard, MD, PhD: Well, well done with your work in this area and I appreciate you joining for your insights today.

Chirag Patel, MD: Thanks again for having us.

Renato Samala, MD: Thank you for having us.

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