A new study suggests that high-frequency spinal cord stimulation offers the best possible pain relief for diabetic neuropathy.
The therapy, Nevro’s HFX system, involves the surgical implantation of a small electronic device near the spine. Thin wires to the spinal cord offer “direct neural inhibition,” blocking the passage of pain signals between the extremities and the brain.
The study, published in Diabetes Research and Clinical Practice, showed that Nevro’s system boasts unmatched efficacy for painful diabetic neuropathy, a condition that is notoriously resistant to medical treatment. After 24 months, the vast majority of participants reported significant and durable pain relief. Speaking to Diabetes Daily, David Caraway, MD, PhD, the chief medical officer of Nevro, called the results “spectacular.”
“Honestly, you don’t see results like that; 90 percent of patients had at least 50 percent pain relief, in a multicenter two-year trial. It just doesn’t really happen.”
The spinal cord stimulation treatment also produced intriguing knock-on effects. In a post-hoc analysis, study participants using the HFX system were found to enjoy both weight loss and better blood sugar control (A1C). The therapy also appeared to improve sensory and neurological function. This unanticipated bonus needs to be evaluated in more-focused trials, but it suggests that high-frequency spinal cord stimulation is not merely masking pain but also addressing peripheral neuropathy in a more profound manner.
Painful Diabetic Neuropathy
Neuropathy is a type of nerve damage common in people with diabetes, ultimately caused by high blood sugar levels (hyperglycemia). Diabetic neuropathy can affect many parts of the body, but it frequently touches the feet and legs first. This nerve damage and dysfunction can be extremely uncomfortable, with patients feeling pain, tingling, burning, or prickling; the pain is often worse at night.
The pain from diabetic neuropathy is also frustratingly difficult to treat. A 2014 study, for example, found that only 14 percent of patients enjoyed significant pain reduction from gabapentin — a commonly prescribed and officially recommended drug therapy — compared with those using a placebo.
Patients who are able to find relief often use a combination of prescription medication, over-the-counter treatments such as ointments, alternative remedies like cannabis, and nonmedicinal techniques such as massage or foot elevation. Sadly, many people with painful diabetic neuropathy find no relief from any of these treatments, and have resigned themselves to the discomfort and pain.
Spinal Cord Stimulation
Spinal cord stimulation involves the surgical implantation of a small device in the back. This device delivers mild electrical pulses along thin wires to the spinal cord. These pulses mask or block pain signals from reaching the brain.
The technique isn’t new; it’s been used for years for many types of chronic pain, such as failed back surgery syndrome. The stimulators typically come with remote controls that allow patients to adjust the type of pain relief they’re receiving.
In the United States, there are three spinal cord stimulation systems currently approved for the treatment of painful diabetic neuropathy. The devices made by Nevro’s two competitors, Medtronic and Abbott, emit a lower electrical frequency that largely masks pain by introducing a tingling sensation known technically as “paresthesia.” Nevro’s high-frequency device, on the other hand, does not cause a tingling feeling. Several studies, of patients both with and without diabetes, have shown that high-frequency stimulation offers more-effective pain relief.
Pain Relief Results
The new study enrolled 216 patients with “refractory” painful diabetic neuropathy: People had already failed to respond to at least one drug treatment. For the first six months, the volunteers were randomly placed into two groups, one receiving the Nevro HFX device, the other receiving conventional care. After six months, patients were allowed to switch treatments if they so desired. Patients subjectively rated their pain levels on the standard scale, choosing a number from 0 to 10. The study continued for a total of two years:
Nevro HFX reduced pain by an average of 80 percent.
Ninety percent of participants experienced greater than 50 percent pain relief.
In the group that originally received spinal stimulation devices, none elected to switch to conventional care after six months.
In the group that originally received conventional care, 93 percent elected to have the Nevro device implanted.
Measures of sleep quality and quality of life similarly improved.
Five patients (3.2 percent) needed to have the implant removed due to infection.
The study also tested for changes in the patients’ sensory, motor, and reflex functions. The results were “surprising even to us,” says Dr. Caraway.
Sixty-six percent of implanted individuals exhibited a “clinically meaningful improvement,” mostly in sensory function. Some participants offered cheerful anecdotes attesting to the change: “These patients would say things like, ‘I can feel the cold tiles on my floor for the first time in years’ or ‘I can feel my socks again!’”
The improvement in sensation is, frankly, difficult to explain. It doesn’t necessarily make any sense that spinal cord stimulation — which is intended merely to block pain signals — would enhance the ability to feel.
“We’ve got several working hypotheses,” Caraway says. For one, perhaps instant pain relief allowed people to perceive sensations that had previously been masked by pain. Some patients claimed to experience sensory improvement almost immediately, and “maybe when you profoundly relieve pain, maybe you’re able to process sensory information better.”
There is also some preliminary, unpublished evidence that high-frequency spinal stimulation helps to increase nerve fiber density. “Maybe we’re having direct effects on pain circuit neurons?”
Nevro has embarked on a new study that will focus on these neurological improvements. Caraway can’t wait to get to the bottom of it: “Is it true, clinically? Let’s do an even better study. If we can show improvement in sensory function, now that makes a big difference. We’ll know more as we progress.”
A1C and BMI
Nevro’s big study was not initially designed to evaluate blood sugar control or weight loss as primary outcomes, but a post-hoc analysis released during June’s annual American Diabetes Association (ADA) scientific conference found that certain subsections of trial participants enjoyed improvements in both measures.
An initial analysis of the overall numbers found that Nevro HFX did not lead to blood sugar improvements. But when limited to patients with a starting A1C of greater than 8.0 percent (those not meeting traditional benchmarks for glycemic control), there was a drop of 1.0 percent after two years that was both “statistically and clinically significant.”
Participants also lost weight. After the full two years, participants had lost an average of 6.8 pounds; those with class 2 obesity lost 11.9 pounds.
It’s unlikely that the device itself caused these improvements directly.
“We don’t think it’s a direct physiological effect,” says Caraway. “It’s probably lifestyle changes. If you’re taking a patient’s pain away, and they’re paying more attention to their hyperglycemia, they’re walking around more, they’re happy, their mood is better, and they’re sleeping better, you can imagine that things are going to get better in terms of A1C and BMI.”
Pain relief, in short, can lead to healthier lifestyles. Caraway shared the story of one participant, a security guard at a major sports arena, whose neuropathic pain affected his mobility so badly that he had resigned himself to being stuck at a desk for the rest of his life. Now he’s walking “18,000 steps a day” and has lost about 60 pounds.
Too Good to Be True?
Some experts, however, caution against taking Nevro HFX’s results at face value. During June’s ADA conference, it became clear that specialists in the study of painful diabetic neuropathy doubted that spinal cord stimulation was quite as effective as the new study implied.
Eva Feldman, MD, PhD, a professor of neurology at the University of Michigan, explained her skepticism: “My concern, which is shared by many neurologists, is that this invasive procedure … has not definitively been shown to be effective beyond a placebo response.”
Dr. Feldman explained that Nevro HFX has never been tested against a placebo. A truly rigorous clinical trial would implant “sham” devices in some volunteers, a measure that Nevro has never taken — and is unlikely ever to take, given that it has already won approval from the U.S. Food and Drug Administration. “Several clinical trials in other disorders with pain, such as migraine, have shown a large placebo effect,” Feldman continued.
Rob Singleton, MD, a professor of neurology at the University of Utah, speculated that the placebo effect could be especially large for a therapy like spinal cord stimulation, which requires both an invasive procedure and ongoing management, far more complicated than a simple shot or pill. It could be that the added investment predisposes patients to be especially hopeful for positive results.
Both experts also expressed skepticism of the claim that spinal cord stimulation could improve sensation. On the conference podium, Dr. Singleton wondered aloud whether those claims were “adequately measured.” Feldman doubted that the connection between spinal cord stimulation and improved neurological function made any sense at all.
A new study suggests that Nevro HFX, a high-frequency spinal cord stimulation system, offers unmatched relief from painful diabetic neuropathy for patients who don’t respond to conventional treatment. Study participants enjoyed remarkable levels of pain relief and enhanced sleep quality, and a majority even seemed to have enhanced sensation in their feet. For some, the improved quality of life translated to both weight loss and better blood sugar control. Some experts, however, caution that the results are less than reliable and that the therapy may not be quite as powerful as the new study implies.