From post-implantation screening to 3 months, those in the active treatment arm reported a mean improvement of 3.03 more hours of on time than the control group with Boston Scientific’s deep brain stimulation device.
Jerrold L. Vitek, MD, PhD
New data from a double-blind, sham-controlled, randomized controlled trial of subthalamic nucleus deep brain stimulation (DBS) offer class I evidence that the method is safe and effective in the treatment of the motor symptoms of Parkinson disease.
The findings 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).
Dubbed INTREPID (NCT01839396) and conducted by Jerrold L. Vitek, MD, PhD, professor and head, department of neurology, University of Minnesota, and colleagues, the study assessed the clinical efficacy and safety of Boston Scientific’s Vercise DBS system, which utilizes multiple independent contact current-controlled (MICC) technology, in 191 patients. Of those, the first 160 were included in this interim analysis.
“We saw that patients [in the active arm] met the primary outcome, which was 3 hours,” Vitek told NeurologyLive. “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 a lead. The lead itself, just putting it in, can have an effect on patients. Most studies that have been done before this never looked at that. They looked at when patients were screened, before they got implanted—so I got myself screening, I got implanted, I’m out 3 months. How did I look before I got implanted?”
Vitek explained that the improvements observed in the active arm from screening to the 3-month mark were “quite a bit better,” registering around 5 hours. “The problem is every study is very different. I leave clinicians with this: when you’re reading a study, you need to compare apples to apples, not apples to oranges. We looked at both screening to the 3-month period, which was about 5 hours or more, and also looked at from baseline to 3 months. That was actually 4.6 hours,” he said.
Additionally, Vitek explained that, per protocol, if patients increased their medication post-implantation, even in light of possible improvements from the device, the on time for those patients was recorded as null.
“The bottom line is that the better number is probably that 4.6 hours, and the other number is from screening to 3 months, where they got better by over 5 hours,” he said. “The amount of good quality time during the day was significantly improved. If you look at those numbers from screening to 3 months, that number is as good or better than most studies to date.”
All told, the improvements equated to a 51% improvement in motor symptoms, as measured by clinicians in Unified Parkinson's Disease Rating Scale (UPDRS) III scores, compared to pre-surgery screening. For the active group, a 6-hour improvement in on time without troublesome dyskinesias was reported, in addition to marked and maintained improvements in quality of life, as measured by Parkinson’s Disease Questionnaire (PDQ-39).
As for safety, 26 serious adverse events (AEs) occurred in the 3-month blinded period in 20 (13%) patients. Of those, 18 were reported in the active group and 8 in the control group. A single death was reported among the 196 patients who received the implant before randomization, which was deemed unrelated to the procedure, device, or stimulation.
Vitek and colleagues noted that future trials are still required to assess any potential benefits of producing a more defined current field using the device’s MICC technology and its impact on clinical outcomes. Notably, 41% of the programs utilized current fractionalization along 2 or more contacts—a unique capability of MICC and the Vercise DBS Systems.
Inclusion criteria stated patients must be aged between 22 and 75 years, have a diagnosis of idiopathic Parkinson disease with >5 years of motor symptoms, and be on stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus, and were then randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period.
Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analyzed by intention to treat, and all patients who provided informed consent were included in the safety analysis. The open-label phase of INTREPID is ongoing with no new enrollment, the authors noted.
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