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."
Personalized Configuration
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.
"Remarkable" Results
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.
http://www.medscape.com/viewarticle/847093?src=wnl_edit_tpal
