Clinical Trial Results for Treatment for Painful Diabetic Neuropathy
Erika Petersen, M.D. discusses her clinical trial on the use of spinal cord stimulation for patients with painful diabetic neuropathy. The results were recently published in JAMA Neurology.
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Learn more about Erika Petersen, MD
Erika Petersen, MD
Dr. Erika Petersen attended the Princeton University, where she majored in European history. She completed her medical studies at the University of North Carolina at Chapel Hill. While undertaking her neurosurgical residency training at the University of Texas Southwestern in Dallas, she completed a research and clinical fellowship in functional neurosurgery at the National Hospital for Neurology and Neurosurgery in London.Learn more about Erika Petersen, MD
Transcription:
Clinical Trial Results for Treatment for Painful Diabetic Neuropathy
Caitlin Whyte: Diabetic neuropathy can be painful for some patients. So today, we are talking about spinal cord stimulation for patients with painful diabetic neuropathy. Dr. Erika Petersen's recent clinical trial was published in JAMA Neurology, and she joins us to discuss the results. Dr. Petersen is a professor in the Department of Neurosurgery at the University of Arkansas for Medical Sciences.
This is UAMS Health Talk, the podcast by the University of Arkansas for Medical Sciences. I'm Caitlin Whyte. So doctor, let's start with the basics here. What is diabetic neuropathy?
Erika Petersen, MD: So diabetic neuropathy is a condition that develops in people who have diabetes, where the longterm exposure to elevated glucose or blood sugar levels causes damage to the nerves, most typically the long nerves in the body. And it presents therefore, first of all, most commonly in the feet, but any nerve in the body can be affected.
Caitlin Whyte: And is it always painful?
Erika Petersen, MD: No. So some people will see neuropathy that means that they have numbness. It can also mean different changes in sensation, feelings of cold, but pain is certainly one of the components of it. And when somebody has sensitivity to touch that should otherwise be normal, for example, just a light brush or putting a sock or pants on, or if it feels uncomfortable to walk on the floor where gravel feels like walking on broken glass. That's a condition that's painful diabetic neuropathy, and that affects millions of Americans.
Caitlin Whyte: Now, you're using spinal cord stimulation for some patients whose symptoms have been resistant. So can you explain to us how this stimulation works, how it's traditionally used and what made you try it for painful diabetic neuropathy?
Erika Petersen, MD: Yeah. So a spinal cord stimulator is a small implanted device similar to a pacemaker. It's a little computer and a battery in a device that sits underneath the skin and the wires travel under the skin from that device into the spinal canal, where they're perched underneath the bone over the surface of the spinal cord and they deliver an impulse into the neural tissue of the spinal cord to change how nerve signals are processed.
The idea here, which originated before in like the 1940s and 1950s, but technology has come a long way since then, was that if you could create a stimulation signal into the spinal cord that you could somehow block the pain messages from traveling from the foot up through the spinal cord to register in the brain. And ultimately, that technology has been refined over time. There have been significant engineering breakthroughs as part of it. And one of those things is that in the US in 2015 spinal cord stimulation using ultra high frequency at 10 kilohertz was FDA approved.
And so the original research there was done at looking at people who have chronic back and leg pain most often after having had several back surgeries. And what they found was that a majority of patients were able to see their pain reduced by 50% or more. Some of those patients who then went on to get stimulators once the device became FDA approved might've had diabetes and their diabetic foot pain also got better, even though the reason they were having a stimulator place was for their back and leg pain related to post-surgical pain.
So we had this interesting indication that maybe patients with diabetic neuropathy that was painful would get better with a stimulator. In addition, there have been stimulators around that used lower frequencies of stimulation somewhere around 60 Hertz frequency, not the 10 kilohertz of this spinal cord stimulator system. And there were suggestion that at 60 Hertz people with painful diabetic neuropathy were also getting some pain relief. So we knew from practical real-world experience as well as some science that was already available using other devices, that there was a chance that these higher frequency stimulators might benefit patients with painful diabetic neuropathy as well.
And so that's what led us to do the research study was we knew that there are a lot of patients who have painful diabetic neuropathy. Those patients unfortunately have tried a lot of medications. Those medicines have a lot of side effects and often even if the patient can get pain relief for a while, they may not stick with the medicine because of the side effects or this medicine itself stops working after a while.
And so knowing that we might be able to offer a non-pharmaceutical option that had some chance of affecting that pain based on some of the other information we have from the spinal cord stimulator experience led us to say, "Why shouldn't we try a high-frequency spinal cord stimulator and see what the impact is on painful diabetic neuropathy?"
Caitlin Whyte: Now, you mentioned your study. Can you tell us about the results? What did you find out?
Erika Petersen, MD: Oh, sure. This was really exciting to me. And I was really grateful to have the opportunity to bring this to our patients at the University of Arkansas. We were one of 18 centers in the US that participated in the study. And ultimately, there were 216 patients who participated in the research study and we randomized the patients into two groups, a group that received conventional medical management, that is the best kind of medications, injections, topical creams, everything that was basically available as the best options available right now; and the other group had conventional medical management, but then we added the 10 kilohertz spinal cord stimulator device as well. And then we compared how well patients did with pain relief at three months and at six months. And we're actually following these patients up to 24 months.
In addition to looking at pain relief, we looked at a few other things, too. We looked at how well people had changes in their quality of sleep. Painful diabetic neuropathy paranthetically is something that really can be bad at night. People can't get rest because they can't put covers over their feet because of how sensitive they are to that burning pain. Additionally, they wake up from sleep. They just really can't get the quality of rest. And so nighttime quality of sleep was an important thing for us to follow.
We also wanted to look at neurological function. How are people's numbness? How was their motor strength? How were their reflexes? How quickly could they walk a fixed distance? And other quality of life metrics as well were those things that we all studied in the research.
What we saw was that at the three-month endpoint, there was a significant difference between the two groups. And we looked at a combination of pain relief, efficacy, as well as safety. We want to make sure that people's neurological symptoms, that is the numbness that they had from their painful diabetic neuropathy, didn't worsen over time.
And so what we saw is that about 5% of patients who were in the conventional medical management arm showed a responder rate that is that they didn't have a change in the neurological symptoms and that they had their pain reduced by at least 50%. So only 5% of patients in the conventional medical management arm were considered responders at that primary endpoint at three months.
In the spinal cord stimulator arm, 76% of patients were responders who had their pain cut in half and didn't have a change in the neurological function. So 76% versus 5%. And then we followed those same patients to the six month timepoint and we saw a similar difference in terms of the 5% who were responders with significant pain reductions versus an 86% responder rate in the stimulator group. So this is a really a very exciting result because now we have evidence that we have something that seems both effective and safe and maybe more durable than medication.
Caitlin Whyte: Well, doctor, anything else you'd like to share on this topic?
Erika Petersen, MD: Yeah, so I think one of the most interesting things that I'm looking forward to finding out more about when we look towards the 24-month timepoint is, first of all, can we show that this is maintained response? The longer that patients can have their pain under control, the better obviously. And so that's why we're following out for the full two years. I know that we're seeing good maintained response up towards 12 months and we'll be able to reveal full data on that pretty soon.
And then the other piece of this is, as I mentioned, the neurological responses. People are reporting that they can feel their feet under them, that they weren't able to feel sharp versus dull when they were standing on a carpet versus on hard floor, for example. Now, they can feel the ground under their feet when they walk. And we had 61% of patients who've had some sort of neurological improvement, whether it was a change in sensation or change in strength after having had the stimulator placed.
And for patients who are at risk of diabetic complications, like foot ulcers and healing problems or potentially even amputations, being able to feel your feet means you can protect your feet from injuries and potentially save yourself from that harm that can be a real worrisome complication of diabetes.
And so we're going to look at those sensory changes again, going out the full 24 months. And we're also working on trying to figure out if we can come up with better science to understand exactly what the mechanism is that is underlying why people's sensation gets better. It's the first time a spinal cord stimulator research study has shown that people's sensation improves with a stimulator. And I'm really trying to figure out exactly what it is that's changing within the nerves and how they're processing those messages that allows people to feel what's happening again. It's really exciting to me.
Caitlin Whyte: Great. Well, Dr. Petersen, thank you so much for joining us today and for doing this important research.
For more information, visit uamshealth.com. And thank you for listening today. This has been UAMS Health Talk, the podcast by the University of Arkansas for Medical Sciences. I'm Caitlin Whyte. Stay well.
Clinical Trial Results for Treatment for Painful Diabetic Neuropathy
Caitlin Whyte: Diabetic neuropathy can be painful for some patients. So today, we are talking about spinal cord stimulation for patients with painful diabetic neuropathy. Dr. Erika Petersen's recent clinical trial was published in JAMA Neurology, and she joins us to discuss the results. Dr. Petersen is a professor in the Department of Neurosurgery at the University of Arkansas for Medical Sciences.
This is UAMS Health Talk, the podcast by the University of Arkansas for Medical Sciences. I'm Caitlin Whyte. So doctor, let's start with the basics here. What is diabetic neuropathy?
Erika Petersen, MD: So diabetic neuropathy is a condition that develops in people who have diabetes, where the longterm exposure to elevated glucose or blood sugar levels causes damage to the nerves, most typically the long nerves in the body. And it presents therefore, first of all, most commonly in the feet, but any nerve in the body can be affected.
Caitlin Whyte: And is it always painful?
Erika Petersen, MD: No. So some people will see neuropathy that means that they have numbness. It can also mean different changes in sensation, feelings of cold, but pain is certainly one of the components of it. And when somebody has sensitivity to touch that should otherwise be normal, for example, just a light brush or putting a sock or pants on, or if it feels uncomfortable to walk on the floor where gravel feels like walking on broken glass. That's a condition that's painful diabetic neuropathy, and that affects millions of Americans.
Caitlin Whyte: Now, you're using spinal cord stimulation for some patients whose symptoms have been resistant. So can you explain to us how this stimulation works, how it's traditionally used and what made you try it for painful diabetic neuropathy?
Erika Petersen, MD: Yeah. So a spinal cord stimulator is a small implanted device similar to a pacemaker. It's a little computer and a battery in a device that sits underneath the skin and the wires travel under the skin from that device into the spinal canal, where they're perched underneath the bone over the surface of the spinal cord and they deliver an impulse into the neural tissue of the spinal cord to change how nerve signals are processed.
The idea here, which originated before in like the 1940s and 1950s, but technology has come a long way since then, was that if you could create a stimulation signal into the spinal cord that you could somehow block the pain messages from traveling from the foot up through the spinal cord to register in the brain. And ultimately, that technology has been refined over time. There have been significant engineering breakthroughs as part of it. And one of those things is that in the US in 2015 spinal cord stimulation using ultra high frequency at 10 kilohertz was FDA approved.
And so the original research there was done at looking at people who have chronic back and leg pain most often after having had several back surgeries. And what they found was that a majority of patients were able to see their pain reduced by 50% or more. Some of those patients who then went on to get stimulators once the device became FDA approved might've had diabetes and their diabetic foot pain also got better, even though the reason they were having a stimulator place was for their back and leg pain related to post-surgical pain.
So we had this interesting indication that maybe patients with diabetic neuropathy that was painful would get better with a stimulator. In addition, there have been stimulators around that used lower frequencies of stimulation somewhere around 60 Hertz frequency, not the 10 kilohertz of this spinal cord stimulator system. And there were suggestion that at 60 Hertz people with painful diabetic neuropathy were also getting some pain relief. So we knew from practical real-world experience as well as some science that was already available using other devices, that there was a chance that these higher frequency stimulators might benefit patients with painful diabetic neuropathy as well.
And so that's what led us to do the research study was we knew that there are a lot of patients who have painful diabetic neuropathy. Those patients unfortunately have tried a lot of medications. Those medicines have a lot of side effects and often even if the patient can get pain relief for a while, they may not stick with the medicine because of the side effects or this medicine itself stops working after a while.
And so knowing that we might be able to offer a non-pharmaceutical option that had some chance of affecting that pain based on some of the other information we have from the spinal cord stimulator experience led us to say, "Why shouldn't we try a high-frequency spinal cord stimulator and see what the impact is on painful diabetic neuropathy?"
Caitlin Whyte: Now, you mentioned your study. Can you tell us about the results? What did you find out?
Erika Petersen, MD: Oh, sure. This was really exciting to me. And I was really grateful to have the opportunity to bring this to our patients at the University of Arkansas. We were one of 18 centers in the US that participated in the study. And ultimately, there were 216 patients who participated in the research study and we randomized the patients into two groups, a group that received conventional medical management, that is the best kind of medications, injections, topical creams, everything that was basically available as the best options available right now; and the other group had conventional medical management, but then we added the 10 kilohertz spinal cord stimulator device as well. And then we compared how well patients did with pain relief at three months and at six months. And we're actually following these patients up to 24 months.
In addition to looking at pain relief, we looked at a few other things, too. We looked at how well people had changes in their quality of sleep. Painful diabetic neuropathy paranthetically is something that really can be bad at night. People can't get rest because they can't put covers over their feet because of how sensitive they are to that burning pain. Additionally, they wake up from sleep. They just really can't get the quality of rest. And so nighttime quality of sleep was an important thing for us to follow.
We also wanted to look at neurological function. How are people's numbness? How was their motor strength? How were their reflexes? How quickly could they walk a fixed distance? And other quality of life metrics as well were those things that we all studied in the research.
What we saw was that at the three-month endpoint, there was a significant difference between the two groups. And we looked at a combination of pain relief, efficacy, as well as safety. We want to make sure that people's neurological symptoms, that is the numbness that they had from their painful diabetic neuropathy, didn't worsen over time.
And so what we saw is that about 5% of patients who were in the conventional medical management arm showed a responder rate that is that they didn't have a change in the neurological symptoms and that they had their pain reduced by at least 50%. So only 5% of patients in the conventional medical management arm were considered responders at that primary endpoint at three months.
In the spinal cord stimulator arm, 76% of patients were responders who had their pain cut in half and didn't have a change in the neurological function. So 76% versus 5%. And then we followed those same patients to the six month timepoint and we saw a similar difference in terms of the 5% who were responders with significant pain reductions versus an 86% responder rate in the stimulator group. So this is a really a very exciting result because now we have evidence that we have something that seems both effective and safe and maybe more durable than medication.
Caitlin Whyte: Well, doctor, anything else you'd like to share on this topic?
Erika Petersen, MD: Yeah, so I think one of the most interesting things that I'm looking forward to finding out more about when we look towards the 24-month timepoint is, first of all, can we show that this is maintained response? The longer that patients can have their pain under control, the better obviously. And so that's why we're following out for the full two years. I know that we're seeing good maintained response up towards 12 months and we'll be able to reveal full data on that pretty soon.
And then the other piece of this is, as I mentioned, the neurological responses. People are reporting that they can feel their feet under them, that they weren't able to feel sharp versus dull when they were standing on a carpet versus on hard floor, for example. Now, they can feel the ground under their feet when they walk. And we had 61% of patients who've had some sort of neurological improvement, whether it was a change in sensation or change in strength after having had the stimulator placed.
And for patients who are at risk of diabetic complications, like foot ulcers and healing problems or potentially even amputations, being able to feel your feet means you can protect your feet from injuries and potentially save yourself from that harm that can be a real worrisome complication of diabetes.
And so we're going to look at those sensory changes again, going out the full 24 months. And we're also working on trying to figure out if we can come up with better science to understand exactly what the mechanism is that is underlying why people's sensation gets better. It's the first time a spinal cord stimulator research study has shown that people's sensation improves with a stimulator. And I'm really trying to figure out exactly what it is that's changing within the nerves and how they're processing those messages that allows people to feel what's happening again. It's really exciting to me.
Caitlin Whyte: Great. Well, Dr. Petersen, thank you so much for joining us today and for doing this important research.
For more information, visit uamshealth.com. And thank you for listening today. This has been UAMS Health Talk, the podcast by the University of Arkansas for Medical Sciences. I'm Caitlin Whyte. Stay well.