Analysis of data from a clinical trial conducted at Vanderbilt suggests that deep brain stimulation (DBS) administered to patients with very early-stage Parkinson’s disease slowed the progression of rest tremor.
The study, published June 29 in Neurology, is significant because it is the first evidence of a treatment that may possibly delay the progression of one of the cardinal features of Parkinson’s disease. However, the study’s authors strongly caution that a larger-scale clinical trial across multiple investigational centers is needed to validate the finding.
“The finding around tremor is truly exceptional,” said David Charles, MD, professor and vice-chair of Neurology and senior author. “What it suggests is that DBS applied in early stage Parkinson’s disease may slow the progression of tremor. Why it is so remarkable is because there are no treatments for Parkinson’s that have been proven to slow the progression of any element of the disease.”
Mallory Hacker, PhD, research assistant professor of Neurology and the study’s lead author, analyzed data collected from the trial that began in 2006, a trial that was controversial because it recruited patients with early-stage Parkinson’s disease for DBS brain surgery. At that time, DBS was approved for only advanced-stage Parkinson’s disease when symptoms were no longer adequately controlled by medication.
Hacker has been able to investigate this unique cohort further in recent years. As part of the trial, patients agreed to be taken off of their Parkinson’s disease medicine, and those who received DBS also agreed to have their DBS stimulators turned off, so investigators could evaluate the progression of their underlying disease. These “wash out” evaluations, which were seven days in duration, occurred at the VUMC Clinical Research Center every six months over a two-year period. An outside evaluator scored the patients, observing videotapes of the patients that were presented out of chronological order and without information about the treatment assignment or whether patients were on or off their therapy. This single-blind evaluation of motor features off all of their Parkinson’s disease treatment was the basis of the Neurology publication.
The DBS group was on average better on the overall motor score portion than the group who were treated with only drug therapy. However, this finding was not statistically significant because the study size was limited by the FDA to 30 participants and therefore not sufficiently powered to determine efficacy.
“Since this was the first early DBS trial, it was unknown whether there were individual motor symptoms very early in Parkinson’s disease that may be more potently improved by DBS,” Hacker said.
The post hoc analysis showed that 86 percent of the drug therapy patients developed rest tremor in previously unaffected limbs over the course of the two-year period, while that occurred in only 46 percent of patients who had received DBS therapy in addition to drug therapy. Four of the DBS patients had rest tremor improvement and rest tremor completely disappeared from all affected limbs for one DBS patient.
The FDA has approved Vanderbilt to lead the next early DBS trial, a large-scale, Phase III multicenter study that will enroll 280 people with very early stage Parkinson’s disease. Seventeen other U.S. medical centers have agreed to participate in that pivotal trial and joined the DBS in Early Stage Parkinson’s Disease Study Group. Hacker serves as executive director of the study group and the launch of that Phase 3 study is expected to begin in 2019.
“This study on Parkinson tremor is an incredibly exciting finding,” Charles said. “It demands that we must now conduct this FDA-approved trial, and we strongly caution that it is not time for patients to be requesting DBS for early stage Parkinson’s. We have to conduct a large multicenter, well-controlled trial exploring its safety and efficacy before drawing conclusions on the optimal stage of disease to consider DBS therapy.”
DBS is typically applied in advanced stage Parkinson’s disease when medications no longer adequately control symptoms. In 2016, the FDA expanded the indications for DBS surgery to include patients with mid-stage Parkinson’s disease, those who have had a diagnosis for at least four years and who have developed motor complications that don’t respond well to medications.
“The field of DBS therapy for Parkinson’s disease is moving toward earlier stages of treatment. Therefore, we must conduct the pivotal trial to ensure patient safety and provide the Parkinson’s community with the best possible medical evidence to guide treatment,” Charles said.
VUMC is one of the world’s top DBS centers, where a multidisciplinary team has provided the therapy to more than 1,000 patients.
