ESOC 2021 | NETS results: transcranial direct current stimulation for upper extremity recovery after stroke
Christian Gerloff, MD, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, shares the results of the ‘Neuroregeneration Enhanced by Transcranial direct current stimulation (tDCS) in Stroke’ (NETS) trial (NCT00909714), a prospective, randomized, placebo-controlled trial testing the safety and efficacy of anodal tDCS to the primary motor cortex of the lesioned hemisphere in the subacute phase after cerebral ischemia. A total of 123 patient were randomized 1:1 to receive standardized rehabilitative training with active stimulation or sham stimulation. The primary endpoint was improvement in upper-extremity function at the end of the intervention period, measured by the upper-extremity Fugl-Meyer assessment (UEFMA). The intervention was well tolerated and both groups showed good recovery. There was no relevant difference in mean improvement of UEFMA from baseline between those who received active stimulation and those given placebo. This interview took place at the European Stroke Organisation Conference (ESOC), 2021.
Transcript (edited for clarity)
It was quite a challenge to recruit patients, but finally we managed to recruit 123 patients. They were randomized 1:1 into the active stimulation arm and into an arm with sham stimulation, and the sham stimulation is also a big advantage of this method, because there’s a technique that you ramp up the current slightly, and then after a while you ramp it down. For the sham stimulation, you ramp it down pretty much immediately after you have ramped it up...
It was quite a challenge to recruit patients, but finally we managed to recruit 123 patients. They were randomized 1:1 into the active stimulation arm and into an arm with sham stimulation, and the sham stimulation is also a big advantage of this method, because there’s a technique that you ramp up the current slightly, and then after a while you ramp it down. For the sham stimulation, you ramp it down pretty much immediately after you have ramped it up. For the active stimulation, you leave it up for 20 minutes and then you go down. The point is that with a few seconds of stimulation, you don’t have any physiological effect, but patients do not feel any difference.
They don’t feel this ramping up and ramping down and they don’t realize that one current stops much earlier. So that’s a big advantage. So it’s really truly blinded, and that’s an exception for these neurostimulation trials, which are very difficult to blind. Now, what we then found was that both groups had very decent improvement of upper arm function. We measured this with a Fugl-Meyer assessment and this, we measured at baseline, and then for the primary end point immediately after the end of the intervention. The intervention lasted for two weeks, basically 10 working days, every day, repeated and combined with a very rigorous standardized physiotherapy rehabilitation protocol.
So after two weeks, we did the first assessment of the Fugl-Meyer arm score. Then we also followed the patients up until actually 12 months after the intervention, after the stroke. In total, we had many different time points. First time point was right after the intervention. So basically after two weeks. The second time point was after 30 days, the third time point was after 90 days, and then after 12 months. In addition to the Fugl-Meyer assessment, we did many other scores: ARAT, nine hole peg test, grip strength, stroke impact scale, quality of life assessment by PHQ-9. So a very deep phenotyping.
In both groups we saw in all scores, a very nice recovery curve. And then primary endpoint and the hypothesis that tDCS creates more recovery, improves recovery and leads to a greater improvement of the Fugl-Meyer arm score, that was not the case. In both arms they improved by approximately nine points on this score, in the intention to treat analysis. Also if we look at the per protocol analysis, there was no difference. The per protocol analysis they improved, both groups improved about 10 points on the Fugl-Meyer assessment for the primary endpoint time. So right after the intervention, and when we looked at other scores, or at day 30, or at day 90 or at 12 months, there was no difference whatsoever between treatment arms.
So that’s the main finding, besides the fact that the safety and the primary safety endpoint, there was also no observation that would give any concerns. So we defined epileptic seizures during the intervention as primary safety endpoint, and we did not see any epileptic seizures, we also did not see any other side effects that were a problem. So nice method, very well feasible because it’s a small battery driven device and the patients showed good adherence. That’s also important, but at the end it didn’t make a difference.
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