The professor and head of the department of neurology at the University of Minnesota spoke to the recent findings of a study of Boston Scientific's multiple independent contact current-controlled device for deep brain stimulation.
Jerrold L. Vitek, MD, PhD
Recently published findings from a double-blind, sham-controlled, randomized controlled trial of subthalamic nucleus deep brain stimulation (DBS) suggest that the device, a multiple independent contact current-controlled (MICC) DBS system from Boston Scientific, is safe and effective in the treatment of the motor symptoms of Parkinson disease.
Conducted by Jerrold L. Vitek, MD, PhD, professor and head, department of neurology, University of Minnesota, and colleagues, the study evaluated the clinical efficacy and safety of the Vercise DBS system in 191 patients with Parkinson disease and motor symptoms. Dubbed INTREPID (NCT01839396), the study showed that from post-implantation baseline to 3 months post-randomization, the difference in mean change in increased on time without troublesome dyskinesias between the active (n = 121) and control (n = 39) groups was 3.03 hours (standard deviation [SD], 4.52; 95% CI, 1.3—4.7; P <.0001).
To find out more about the device itself and how this MICC technology can offer clinicians more than standard DBS tech, NeurologyLive reached out to Vitek, who offered his perspective and experience with the device.
Jerrold L. Vitek, MD, PhD: Well, I think the device companies in general, if they want to get FDA approval so they can commercialize their devices, they have to go through a trial as part of the FDA approval. They need to show it is safe and effective, even if they make a minor modification their device compared to another device that's already on the market. The 3 device companies so far that have FDA approval that I'm aware of all I had to do a clinical trial.
Medtronic started with the first 1, Abbott did another, and now Boston Scientific did this one. They did have a unique system in the sense that there are multiple current sources for each of the contacts that are on the lead, whereas every other device out there is a single current source.
Well, we always debated this when we first got these devices years ago, with Medtronic, the first group to put it out, it was voltage-controlled, not current-controlled, and it was a single source. If the resistance around the contact we're actually activating and initiating the current from impedance changes, then the amount of current flow changes. It may vary based on the resistance around the electrode. Some people have shown how that can change over time, usually the most changes are the first couple hours, but sometimes you can see those changes over a longer period. Let's say I set your stimulator at a certain level, and that gives you a good control, but all of a sudden, the resistance around the electrode increases over time, then you get less current delivered and then your symptoms may start to come back. And then you're going to come back and see me and then we'll need to adjust it again.
But with constant current device, the nice thing about that is that you can just set the current and you're going to get that a lot of current no matter what the resistance is. Now, there are other constant current devices out there now. But this was one of the first devices that actually did it. And the fact that they can control the amount of current that goes across each contact— and in this particular device, they had 8 contacts. There's something new out there as well called a segmented lead now, which actually has 8 contacts, but it's set up so that it’s 1 circular contact, like metal circle, and then there's 3 segments on the next one, 3 segments on the next one, and then 1 of the bottom one—called the 1-3-3-1. Boston has that device now, but that's not what the trial was. This trial was with 8 contacts, 1 stacked on top of the other. And again, the benefit here was that we could put as much or a little current across each contact.
The idea then if you stimulate across one contact, you get a ball of current. But with this, what you can do is you can actually make the ball as big or as small as you want to. So that was nice because you might have contact that's really near an area that you don't want a very big ball current, you want just a little bit because you can kind of fine-tune it. Then you could turn on a little bit of current and get a small ball, then just above that the contact could be a little bit bigger, and maybe the one above that you can get a little bit smaller, or you combine the two, right? You got a lot of options in terms of shaping the current field. The kind of structures we put them in, they're not like big circles, they have a geometric shape. And then wherever your lead ends up you may want to make a smaller ball or a bigger ball in different places. It gives you that flexibility.
Now that they have this new 1-3-3-1 out, Boston Scientific and Abbot both have this lead, but now, Boston has the ability to put current across a segment in one direction rather than put it in 1 of those 8 contacts, which is just going to be a ball about now they can shift it in different directions. This study was pretty much 8 contacts, 1 on top of the other, and you can control how much current through each contact. That was the advantage.
You know, there have been a lot of studies, if you were to look at PubMed and put in deep brain stimulation, you'd be surprised. There has been an exponential increase in the number of studies. But there's really only been a handful of randomized controlled trials, and only a few that have been blinded. One study years ago is single-blinded, which meant the person that was evaluating the patient was blinded, but the patient wasn't. So, the patient knew what they were getting. There are other studies where things were double-blind—really only 1 that I'm aware of—but they didn't have a sham control. By that, I mean, you everybody got implanted, and then nobody knew who was turned on or not.
We had a sham control in which we put the lead in but didn't turn it on. But we tried to make the patient think it was on because of the sole issue of the placebo effect. If I convince you you're going to get something, a lot of people they improve just by your being convinced you're better. So, this really helps to control for that placebo effect. This is really the only trial that was double-blind and randomized with a sham control. It's the only one that was done. So really, it offers a unique data set, class I evidence for sure, and kind of one of a kind right now. You're really not going to find a study like this funded by the NIH right now because of the fact that it's expensive. But the companies want to get their device in the market, so as a scientist I'm kind of loving it that I can get into this study and company's going to pay for it, and we can do some unique things with the studies.
No. I mean, we were hoping we would find the outcomes we saw. One of the things people generally look at when they're doing these kinds of studies is, we look at the number of waking hours that the patient has good quality time. We measure that by, when they're on their medication, the symptoms are improved. We call that on. When you're off, that means the symptoms are really kind of manifesting—they get worse. That's called an off time. The other part about being on is in Parkinson disease, you go from a position where you have very little movement, you're slow, you're stiff, you may have this tremor, the shaking that people get—that's obviously not good on time for folks. When they turn on, it gets better and it goes away largely. Sometimes, it doesn't go away as much as you'd like it to, but it can be replaced by an excessive movement called dyskinesia. You go from a poverty of movement when you're off to on, and then as people get more advanced, they get complications, so-called dyskinesia.
What we looked for was, what's the on time? How much more on time did they get without the dyskinesia? And the primary outcome measure was that: how much better did you get from baseline after the lead was implanted compared to 3 months later. When they did the blinded ratings, we saw that they met the primary outcome, which was 3 hours. Now, most studies have seen more than that—4 hours, 4.5 hours. This study was very different in the sense that we looked after we implanted the lead. The lead itself, just putting it in, can have an effect on patients. And most studies that have been done before this never looked at that. What they looked at was when they were screened, before they got implanted. So, I got myself screened, I got implanted, I’m out 3 months—how did I look before I got implanted? If you look at these patients from screening to 3 months after they were implanted, it was more like 5 hours. So, it's quite a bit better.
The problem is every study is very different. What I leave clinicians with is, when you're reading a study, you need to compare apples to apples, not apples to oranges. We looked at both the screening to the 3-month period, which was like about 5 hours or more, and also looked at from baseline to 3 months, that was actually 4.6 hours. It gets complicated because the FDA told us that if anybody in our in our group increased their medication after they were implanted—even though they might have improved their on time—we had to count their on time as a 0 . So even though they got better, the rule was you had to call it a 0. That's where the number of 3 hours comes in. The bottom line is the better number is probably 4.6 hours and then the other number is actually screening to 3 months, where they actually got better by over 5 hours. The amount of time good quality time during the day was significantly improved.
If you look at those numbers of screening to 3 months, that number is as good or better than most studies to date. That's double-blind—nobody knows what's going on. Most of the studies are really open label, so I know they got implanted and they know they got implanted. There's that little placebo effect kind of a bias that's inherent in open-label studies. That was 1 thing.
The other major finding that people look at usually is how do we assess when they're not taking their meds and they're completely off their meds? How much does stimulation really help them? There's a rating scale that looks at rigidity, slowness, all the motor signs of Parkinson, and you write them 0 to 4, and you get a number. Then, you basically told all those numbers up and say, “Okay, we're at a 43 when I'm off medication, when I turn on my stimulator, what do I go down to? What percent improvement do I see?” That's what you look for. In this study, at 3 months in the blinded phase, it was 42% better. That's very comparable to studies that are even open label, frankly. So, we are very pleased with that. As they went further out in the open-label phase, that was reaching up into 50% to 51%, but then you don't know is it really because we got better at programming or is it because there's a little bit placebo effect—it's hard to say. But I think the fact that the double-blind, randomized portion of the showed 42% was pretty good. We're pretty happy with that.
Transcript edited for clarity.
Vitek JL, Jain R, Chen L, et al. Subthalamic nucleus deep brain stimulation with a multiple independent constant current-controlled device in Parkinson's disease (INTREPID): a multicentre, double-blind, randomized, sham-controlled study. Lancet Neurol. 2020;19(6):491-501. doi: 10.1016/S1474-4422(20)30108-3