Long-term adaptive deep brain stimulation (aDBS) at home compares favorably to the standard of care for patients with Parkinson’s disease, a pivotal clinical trial indicates.
Researchers report that the tailored therapy, which automatically adjusts the amplitude of stimulation in response to changes in relevant neural activity, was tolerable, effective, and safe compared with continuous (c)DBS when each was combined with medication.
“Delivering adaptive neurostimulation chronically, in response to a personalized neural physiomarker, is both technically and clinically possible, laying the foundation for the wider clinical application of aDBS,” reported Helen Bronte-Stewart, MD, from Stanford University, and co-workers.
Results from the international, multicenter Adaptive DBS Algorithm for Personalized Therapy in Parkinson Disease (ADAPT-PD) pivotal trial are published in JAMA Neurology.
cDBS is the standard of care in Parkinson’s disease, with currently available devices delivering continuous neurostimulation at one constant amplitude.
While adding cDBS to medication improves outcomes, it can neither respond to dynamic fluctuations in symptoms and nor natural or medication-induced fluctuations in underlying neural activity.
This results in overtreatment for some people when medications are at their peak dose or undertreatment as medications wear off.
aDBS, by contrast, automatically adjusts parameters in response to fluctuations in neural activity or behavior to control symptoms in a more stable way, reducing adverse effects, and potentially increase neurostimulator battery longevity.
Small, single-center studies had already demonstrated feasibility and efficacy of short periods of aDBS under clinical observation and the ADAPT-PD trial investigated its value in the long term.
The trial assessed at-home treatment driven by local field potential (LFP) power from frequencies within the α-β band (8—30 Hz) in 68 people with Parkinson’s disease who were previously stable receiving subthalamic nucleus or globus pallidus internus (GPi) cDBS treatment and medication.
As no at-home aDBS data existed at the time of trial design, the objective was to demonstrate the tolerability, efficacy, and safety of two previously reported aDBS modes in this setting: single threshold (ST-aDBS) and dual threshold (DT-aDBS).
The primary objective was that at least 50% of participants would meet a performance threshold based on the change in on-time—when symptoms were well controlled—without troublesome dyskinesia as assessed using a self-reported diary with no less than a one standard deviation reduction while receiving aDBS compared with cDBS, both stable with medication.
The secondary objective was to assess the energy efficiency in terms of total electrical energy delivered (TEED) with the two aDBS modes compared with cDBS.
Participants had a mean age of 62.2 years and those who tolerated two aDBS modes were randomized and blinded to 30 days in each mode, in a single crossover design. Those who tolerated only one mode were assessed in that mode only and participants were given the option of continuing in their selected aDBS mode for long-term follow up of 10 months.
Overall, 40 participants were assessed with DT-aDBS and 35 with ST-aDBS.
The study met its primary and secondary end points, with most aDBS participants experiencing comparable on-time without troublesome dyskinesia compared to stable cDBS.
The primary end point performance goal was met in 91% of the DT-aDBS group and 79% of the ST-aDBS with the post hoc performance threshold of a less than two hours per day reduction. The two aDBS modes differed in neither the primary nor secondary outcome.
TEED was lower during ST-aDBS compared to cDBS, with a mean reduction of 15%, but did not significantly differ to DT-aDBS.
There were no serious device-related adverse events, and all but one relating to stimulation resolved during the aDBS setup and adjustment phase, with no serious device adverse events during long-term follow-up.
Exploratory clinical outcomes suggested improvements in on and off time, as well as in motor severity with DT-aDBS and selected mode compared to stable cDBS.
“To our knowledge, these results are the first to show that long-term at home STN or GPi aDBS, driven by LFP power in the eight- to 30-Hz range and using algorithms embedded on an implanted system, was tolerable, safe, and effective relative to standard of care cDBS,” the researchers concluded.
