The next abstract, again a late-breaking abstract, is entitled Intrepid, a Prospective Double-Blinded Multicenter Randomized Controlled Trial Evaluating DBS with a New Multiple Source Constant Current Rechargeable System in Parkinson's Disease, presented by Dr. Gross and discussed by Dr. Abosh. Thank you. I promise this talk will be more stimulating than the last. So it's my honor to present the results of this double-blind, randomized trial of DBS, of a new system, on behalf of the PIs Phil Starr and Gerald Vitek, who's a neurologist from the University of Minnesota, the clinical investigators in this multicenter trial, and the company Boston Scientific that sponsored it. These are my disclosures. As soon as I figure out how to operate this thing... The study objective was to evaluate the safety and effectiveness of this new DBS system for Parkinson's disease. There are unique features to this new system. It has multiple independent current-controlled sources, such that each electrode contact can be individually activated and increased in its intensity as compared to the other contacts. It has a lead design which includes the usual tight spacing, but it has eight contacts to increase the flexibility. It's rechargeable and has a nice, small footprint, gentle contours, and it has wireless patient-user interface, which makes it easy to use. There are unique aspects to the clinical trial that we ran, in particular. This is the first double-blind, randomized, stimulation-controlled trial ever run for Parkinson's disease, and that's quite unique. It uses a post-implantation baseline where, instead of using the screening point, we use the patient's scores after the implantation is performed as the baseline, which controls for implantation effects. The control group received SAM stimulation, and importantly, there was no increase in medication allowed during the blinded evaluation period, and any patients that had an increase in their medication during that period of time had their scores zeroed out for that period. So the patients underwent implantation after being screened, and then they were randomized at the point two to four weeks after implantation. They then underwent the randomization evaluation period, and then after twelve weeks, underwent the open-label period that extends all the way out to five years, and I'll be presenting first the blinded evaluation period, and then the one-year results. The primary outcome measure for the trial was the difference in the mean change from baseline to twelve weeks post-randomization between the treatment and control groups, and the primary outcome variable was the mean number of waking hours per day that comprised good on-time without troublesome dyskinesias, as measured by a Parkinson's disease diary, which was another challenging aspect of the study. The key inclusion criteria are fairly typical. Patients had Parkinson's disease for greater than five years, and a modified honing ER of greater than two, and a UPDRS motor subscore of greater than 30. They had to have greater than six hours per day of poor function. That included off-time and on-time with troublesome dyskinesia, and they had to have a greater than 33 percent improvement in their motor subscore of the UPDRS scale. These are the results after the twelve-week blinded evaluation period. These are the demographics for the patients, and the active and control groups were fairly well-matched. There were 160 patients in this phase of the study. They were mainly male, and they had a UPDRS score of 43.4, improving to 18.5 with medication during the screening phase. Their disease duration was ten years, which is fairly typical, and this gives an idea of exactly how bad off they were. Their off-time was about seven hours per day, and on-time with troublesome dyskinesia, 4.35 hours. So this is the primary endpoint of the study at twelve weeks through the blinded evaluation period, and it was a successful study. It met its primary outcome point and was statistically significant. This shows the results on the left. This depicts the on-time without troublesome dyskinesia. That is good quality on-time, and it goes from 7.78 in the active stimulation patients in their post-randomization baseline up to 12.37 hours, which is a 3.7 hour increase in good quality on-time. In comparison, the control group improved very minimally for a difference of three hours between the two groups. If you include the patients that were not included because they had an increase in medication, for those patients they had that increase in on-time noted as zero, which is a very conservative mark. If you include those patients in this study, then in fact the on-time improved by even a greater amount, increasing by 4.6 hours in the active stimulation group for a 3.71 hour difference between active and control groups. The study also met a number of the various secondary endpoints, including improvement in the UPDRS motor score in the stimulation on medication offstage, the change in various activities of daily living and quality of life measures, as shown here, and the clinical global impression of change based on the subject and the physician also improved significantly. And the patients were satisfied at 12 weeks. This shows the one year results, and I'll concentrate on this phase over here, after the blinded evaluation period when all patients underwent open label optimization. And this shows the UPDRS motor scores at screening at 43.4, which I showed you before, and that improved by 49.2% to their point at 52 weeks. And as far as the change in their on-time based on the PD diary, it went from 7.3 hours to 13.4 hours, an increase in six hours of on-time after one year of study time. As compared to other clinical trials which have been done before, we saw a greater amount of on-time improvement in this study. Notably, this is a double blind evaluation. None of the other four studies had double blind evaluations. Quality of life improved in almost all metrics at 26 weeks and 52 weeks in the study. And as far as safety goes, there were 103 serious adverse events. No unanticipated adverse events. There were three deaths that were unrelated to the device, the procedure, or the stimulation. This shows the serious adverse events in our study population, all of the patients included out to one year, including 191 subjects. There was a 1.6% rate of serious adverse event related to intracranial hemorrhage, which is quite moderate. And as far as infection goes, there was just under a 5% increase in serious adverse events related to infection. So to conclude, the study successfully met its primary outcome point and several of the secondary outcome measures. There was a mean increase in three hours and a very conservative estimation between active and control groups in on-time without troublesome dyskinesia, with no increase in Parkinson's medications in that group. And at one year follow-up, there was a nearly 50% improvement in the motor subscore of the UPDRS3 and a six-hour improvement in the total on-time. And significant improvements in medication reduction and overall quality of life as well. And the safety profile of this new device was comparable to other published studies. So I thank you for your attention. So the INTREPID trial was a carefully designed, well-executed, multi-center, double-blind, randomized control trial. It was designed to evaluate a DBS system that is new to the American market in the setting of bilateral subthalamic deep brain stimulation for the treatment of Parkinson's disease. It's worth noting that the study device used does not have MRI conditionally safe labeling. It featured a traditional concentric ring electrode design and not their steerable current technology. And it did not allow the patients involved in the study the freedom to choose a non-rechargeable battery. All of which are device features currently available outside the United States and we hope to soon have access to here. Nonetheless, the study did, as you heard, meet its primary and secondary endpoints. There were no unexpected adverse events and the rate of device and procedural serious adverse events was comparable to publications that have already appeared in the literature for other manufacturers. So nothing earth-shaking about these results, but after two decades with only one DBS manufacturer available in the United States, it's good for our patients and crucial for moving forward the field to have access to other devices. Thank you.

Intrepid trial

double-blind

randomized controlled trial

deep brain stimulation

Parkinson's disease