BALTIMORE — Patients with Parkinson's disease treated with deep-brain stimulation (DBS) in the early stage of disease show significant improvements in motor skills extending out to 5 years of follow-up, offering encouraging, though preliminary, evidence that the known benefits seen in advanced and midstage disease could also apply to earlier stages.
"We found that not only is DBS combined with medicine better than medicine alone, but we have this longitudinal data showing a sustained benefit for 5 years," senior author David Charles, MD, professor and vice-chairman of neurology and chief medical officer of the Vanderbilt Neuroscience Institute at Vanderbilt University Medical Center, in Nashville, Tennessee, told Medscape Medical News.
"Even with these small numbers of patients, the separation favoring DBS is dramatic, so this is very encouraging," he said.
The results are from a 5-year follow-up of patients in a pilot study that paved the way for a phase 3 pivotal clinical trial on the treatment in early-stage disease that is being led by the Vanderbilt team.
Findings from the initial 2-year pilot study were reported in the journal Parkinsonism and Related Disorders, and the new findings, presented here at the American Neurological Association (ANA) 2016 Annual Meeting, provide a longitudinal update of follow-up on the patients at 5 years. The new findings were presented by coauthor Mallory Hacker, PhD, assistant professor of neurology at Vanderbilt University Medical Center.
For the initial study, patients who had been receiving a medication for no more than 4 years and with no dyskinesias or other motor fluctuations were randomly assigned to treatment with subthalamic nucleus DBS plus optimal drug therapy or to optimal drug therapy alone.
The patients had similar baseline symptoms according to Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor scores.
Follow-up evaluation after an initial 2-year follow-up period and annually for an additional 3 years showed that those in the DBS group (n = 8) had improvement in average UPDRS scores from baseline at each follow-up visit through the 5 years.
In contrast, patients receiving drug therapy alone (n = 9) had a 27% increase in motor scores compared with baseline at the 5-year evaluation (P = .04).
Patients who received DBS had average changes in motor scores from baseline that were 9.9 points less than those in the medication-only group at the 4-year follow-up and 8.9 points less at the 5-year follow-up (P = .04 and P = .03, respectively).
"This therapeutic advantage imparted by DBS in early stage Parkinson's disease exceeds a moderate clinically important difference in the UPDRS Part III motor score," the authors said.
Importantly, Dr Charles noted that more patients in the DBS group were maintained with monopharmacy alone.
"The majority of the DBS group remained on monopharmacy whereas the majority of people in the medication group required polypharmacy, with 2 or more different kinds of Parkinson's disease medicines to manage symptoms."
Other data from the study that are being evaluated include information on quality of life; other functions, such as cognitive effects; and safety.
DBS has approval from the US Food and Drug Administration (FDA) for the treatment of advanced and midstage Parkinson's disease, in which it has shown potentially dramatic improvement. The goal of the upcoming clinical trial will be to evaluate the effects of the treatment in a very early stage of the disease, before its often devastating consequences set in.
"The quest of this line of research is to understand a simple question: If DBS is applied in very early Parkinson's disease, will it slow the progression of the disease?" Dr Charles said.
Although the risk is low, initial concerns of DBS surgery included the potential of brain injury and even death, and there were therefore significant concerns about whether patients with early-stage Parkinson's disease would even be willing to enter such a trial, but Dr Charles said the enthusiastic response has in fact been encouraging.
"I can tell you that over the 5 years there have not been any deleterious effects in terms of stimulation, and there was only one missed visit. It was remarkable how extremely comitted the patients were to seeing this project through to the end."
The phase 3 trial, to involve 280 patients at 18 centers, is expected to begin in 2017.
The study received funding from Vanderbilt CTSA grant UL1TR000445 from the National Center for Advancing Translational Sciences (NCATS), NCATS/National Institutes of Health (NIH) award UL1TR000011, NIH R01EB006136, Medtronic Inc, and the Michael J. Fox Foundation for Parkinson's Research. Dr Charles receives income from Allergan, Ipsen, Concert, and Medtronic for consulting and education services. Other authors also disclosed research or consulting relationships with Medtronic.
American Neurological Association (ANA) 2016 Annual Meeting. Abstract S105. Presented October 18, 2016.
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Cite this: Motor Skill Improvement With DBS Seen in Early Parkinson's - Medscape - Oct 27, 2016.