One-year INTREPID results show efficacy

A deep brain stimulation system (DBS) with a novel device reduced symptoms in patients with Parkinson’s disease (PD), an interim analysis of the INTREPID study showed.

The Vercise System (Boston Scientific) met its primary endpoint, with a significant mean difference between the active and control groups in time spent in dyskinesia-free “on” time at 3 months (3.03 hours from baseline, 95% CI 1.3-4.7; P<0.0001), reported Jerrold Vitek, MD, of University of Minnesota and colleagues in Lancet Neurology.

The stimulator system, approved in the U.S. in 2017, includes a novel multiple independent contact current-controlled (MICC) device with programmable current field to allow change in the stimulation area, in comparison with single-current systems.

“This double-blind, sham-controlled, randomized controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson’s disease,” Vitek and colleagues wrote.

“Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes,” they added.

In an accompanying editorial, Gunther Deuschl, MD, PhD, of the Christian-Albrechts-University in Kiel, Germany, and Paul Krack, MD, PhD, of the University of Bern in Switzerland, wrote, “Overall, this first double-blind study in the field is a further important milestone in the framework of evidence in favor of subthalamic nucleus DBS. This will certainly contribute to homogenize practice of DBS worldwide.”

The INTREPID study enrolled idiopathic Parkinson’s disease patients from May 2013-Nov. 2017 across 23 sites. Participants had over five years of motor symptoms and were 22-75 years old, with stable medication regimens from 28 days prior to consent.

The interim, intention-to-treat analysis considered the first 160 randomized patients who had bilateral subthalamic nucleus implants and were randomly assigned 3:1 to therapeutic (active, n=121) or sub-therapeutic stimulation settings (control, n=39) for three months.

During the three-month blinded period, patients were not allowed to increase their anti-parkinsonian medications, per study protocol. After the blinded phase, all patients received active treatment in the open-label period for up to five years. The present analysis included data to one year.

The primary outcome was patient diary-determined difference in mean change from baseline visit to three months in mean daily waking hours with good symptom control, no troublesome dyskinesias, and no increase in anti-parkinsonian medications. Secondary outcomes included changes in Unified Parkinson’s Disease Rating Scale (UPDRS) part III scores.

Mean age was about 60 and 73% were men, with average disease duration of about 10 years. Mean baseline UPDRS III “off” scores with medication were 43.4 (moderate disease).

At 3 months, UPDRS III scores (motor examination evaluated by the clinician) improved by an average of 42% in the medications “off” and stimulation “on” condition (P<0·0001) in the active group, compared with screening.

Individual motor scores for tremor (61%), rigidity (51%), bradykinesia (32%), and gait (39%) significantly improved in the medications “off” and stimulation “on” condition (P<0.0001), while tremor and rigidity were also significantly better in the medications “on” and stimulation “on” condition (P=0.0006 for tremor; P<0.0001 for rigidity).

Serious adverse events by 3 months included 26 events in 20 patients: aphasia (n=1), post-operative confusion (n=4), seizure (n=2), infection (n=9), hypoventilation (n=1), implant site edema (n=2), intracranial hypotension (n=2), myocardial infarction (n=1), pneumocephalus (n=2), fever of unknown origin (n=1), and wound hemorrhage (n=1). Of these 26 events, 18 events were in the active group and eight were in the control group.

“The site of hardware infection was cranial in all seven patients, one of whom also had evidence of infection involving the implantable pulse generator pocket,” Vitek and colleagues wrote.

Based on Columbia Suicide Severity Rating Scale (CSSRS) scores, 4 patients (3%) developed mild, de novo suicidal ideation by 3 months, all in the active group. There were no completed suicides, but one suicide attempt reported in the active group resulted in the surgical revision of one brain lead. “Following reposition of the lead posteriorly, based on possible effects in non-motor regions of the subthalamic nucleus, mood effects were ameliorated,” the researchers noted.

Serious adverse events from three to 12 months included implant site edema (n=2), wound infection (n=1), wound dehiscence (n=2), and mania (n=1).

By 1 year, mean UPDRS III score was 21.3, compared with 43.4 at screening. INTREPID’s “remarkable 51% improvement in UPDRS III at 1 year are among the best results reported for any subthalamic nucleus DBS trial, corroborating the choice of subthalamic nucleus as the preferred target for treatment of poor mobility,” the editorialists wrote.

The study design had limitations: clinicians tended to use more MICC during follow-up, but the study did not show the rationale for this, the researchers pointed out.

“Another limitation is that we were not able to characterize the extent of possible microlesion effects, as we did not complete assessments during the stimulation ’off’ and medications ’off’ condition after device activation,” Vitek and co-authors noted.

  1. A deep brain stimulation system (DBS) with a novel device reduced symptoms in patients with Parkinson’s disease (PD), an interim analysis of the INTREPID study showed.

  2. The stimulator system, approved in the U.S. in 2017, includes a novel multiple independent contact current-controlled (MICC) device with programmable current field to allow change in the stimulation area.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was funded by Boston Scientific.

Vitek serves as a consultant for Medtronic, Boston Scientific, and Abbott, and serves on the scientific advisory board for Surgical Information Systems.

Deuschl reports personal fees from Boston Scientific, Cavion, Functional Neuromodulation, and Thieme Publishers; and grants from Medtronic and the German Research Council, outside the submitted work. Krack reports grants from the Swiss National Science Foundation, Roger de Spoelberch Foundation, Bertarelli Foundation, Michael J Fox Foundation, Annemarie Opprecht Foundation, and Parkinson Schweiz; research grants from Boston Scientific and Aleva; lecturing fees paid to employing institution from Boston Scientific; and reimbursement of travelling expenses to scientific meeting by Zambon, outside the submitted work.

Cat ID: 37

Topic ID: 82,37,730,37,192,925