June 26, 2015
The first clinical study with a new-generation system of deep-brain stimulation (DBS) for Parkinson's disease has shown promising results.
The VANTAGE study, published in the July issue of Lancet Neurology, evaluated a new "multiple-source" DBS system (Vercise, Boston Scientific).
"DBS is quite popular now for advanced Parkinson's with motor fluctuations, and has shown particular benefits in younger patients and those who are cognitively well," lead author, Professor Lars Timmermann, MD, University Hospital Cologne, Germany, told Medscape Medical News.
He explained that the current systems in use consist of one electrode implanted in each hemisphere of the brain, with each electrode having four contacts, and a bulky stimulator implanted in the chest. "It is a good workhorse, but this new system that we are now testing is much more sophisticated."
The new system has eight contacts in each hemisphere that can deliver a much higher degree of stimulation with a smaller device. Each contact can be programmed individually to deliver as much current as required, so the electrical field can be configured individually in each patient.
"The first-generation DBS devices are limited somewhat by the potential for side effects caused by electrical stimulation to areas of the brain near to the target zone," Professor Timmermann added. "This limits the dose of electrical stimulation that can be given. With the new system we can minimize current in certain areas and maximize stimulation in other areas to obtain a full clinical effect. In this first-in-man study of the new device, we wanted to see if these refinements would translate into better clinical effects and it looks as though they do."
He noted that the previous DBS clinical trials have shown an improvement in motor symptoms of 25% to 40%. "But the new device showed a 60% improvement in this study, and this was accompanied by considerable improvement in quality of life, and a 50% reduction in medication. Also we didn't have a single nonresponder, which is remarkable. Taken together the results are very exciting — truly motivating."
The new system is CE mark approved in Europe and is offered in about 20 European centers. "This is the first evidence that it really works," Professor Timmermann said. "We are very happy with the results."
For the VANTAGE study, 40 patients received a bilateral implant in the subthalamic nucleus. The primary endpoint — Unified Parkinson's Disease Rating Scale (UPDRS) III motor score 6 months after implantation — showed a significant reduction to 13.5 from 37.4 at baseline. In addition, use of antiparkinsonian drugs was reduced by an average of 58% during the study and on time was extended by a mean of 3.5 hours per day at 52 weeks.
In terms of adverse events, one patient died of pneumonia 24 weeks after implantation; this death was judged to be unrelated to the procedure. There were 125 adverse events reported, the most frequent of which were dystonia, speech disorder, and apathy. Three serious adverse events were attributed to the device or procedure (one case each of infection, migration, and respiratory depression), all of which resolved without residual effects and stimulation remained on during the study.
In an accompanying editorial, Michele Tagliati, MD, Cedars Sinai Medical Center, Los Angeles, California, describes the results of the study as "remarkable."
He says the 62% average improvement in UPDRS motor scores during the study "is better than in any other reported trial of DBS of the subthalamic nucleus," and "[t]he few serious adverse effects recorded confirm previously accepted levels of surgical safety."
He points out a few limitations of the study, including the small number of patients, the nonrandomized open-label design and unblended assessments.
Both Professor Timmermann and Dr Tagliati suggest that further benefits are likely as this technology continues to evolve.
"We think this is the technique for the future but this is just the beginning — many more fantastic developments are being investigated," Professor Timmermann said. "These include steering the current in different directions to have even more effect and the development of devices that stimulate only when needed. These would read the rhythms in the brain and deliver stimulation only when necessary."
Dr Tagliati concludes: "In the end, the future of DBS as a clinical and translational science will depend on our ability to unravel its mechanisms of action. Only when we better understand and control — versus empirically guess — the effects of DBS on the CNS [central nervous system] will the revolutionary power of this technology fully exert its therapeutic promise."
The VANTAGE study was funded by Boston Scientific, and three of the coauthors are employees of the company. Professor Timmermann has received research grants; personal fees for consultancy, travel, and speaking; and nonfinancial support from Boston Scientific. Dr Tagliati has received consulting fees and research support to his institution from Boston Scientific.