Trial data advance understanding of adaptive DBS in Parkinson’s
Brain signals in most patients strong enough to trigger deep brain stimulation
Nearly all people with Parkinson’s disease taking part in Medtronic‘s ADAPT-PD trial had symptom-related brain signals strong enough to trigger adaptive deep brain stimulation (DBS), known for short as aDBS, according to early data.
Among the findings: that results were similar regardless of disease severity or the location of DBS electrodes in the brain.
“This clinical trial and associated methodology … represents a significant advancement in our understanding of aDBS therapy for Parkinson’s disease,” Scott Stanslaski, the study’s lead author and senior distinguished engineer at Medtronic Brain Modulation, said in a press release.
The study detailing those results, titled “Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial,” was published in the journal npj Parkinson’s Disease.
Medtronic testing adaptive DBS therapy in ADAPT-PD trial
DBS is a well-established surgical treatment for Parkinson’s that uses a small pacemaker-like device placed under the skin of the chest or abdomen to deliver electrical stimulation to specific parts of the brain. It’s typically used to treat Parkinson’s motor symptoms when pharmacological treatments are no longer effective.
In 2021, Medtronic launched a clinical trial called ADAPT-PD (NCT04547712) to investigate the efficacy and safety of adaptive deep brain stimulation, or aDBS, compared with conventional DBS, called cDBS. Unlike cDBS, which delivers constant stimulation but is unresponsive to fluctuations in symptom severity, aDBS automatically adjusts signals based on individual responses.
“This groundbreaking trial is led by our exceptional Medtronic Brain Modulation research, development and clinical teams in close partnership with more than a dozen world renowned neurologists and neurosurgeons from globally recognized academic institutions,” Stanslaski said.
The trial enrolled 68 adults with a mean age of 62.2, of whom 20 (29.4%) were women. DBS electrodes connected to Medtronic’s Percept PC neurostimulator were placed in either one of two brain regions important for voluntary movement — the subthalamic nucleus or the globus pallidus internus.
Participants were monitored over four phases for 15 months, or 1.4 years. The phases were an initial (baseline) examination, DBS setup and adjustment, evaluation, and long-term follow-up. Patients also were offered extended aDBS therapy after the follow-up period.
Now, researchers used this new study to report preliminary aDBS sensing data from the trial’s screening and enrollment phase. The data focuses on detecting brain wave signals called local field potentials, or LFPs, from participants. These signals, associate with the severity of Parkinson’s symptoms, reflect a patient’s responses, allowing the aDBS to adjust stimulation to provide the most effective treatment.
Detection of [a needed brain wave] signal may be sufficient for aDBS programming in the large majority of patients without necessitating medication withdrawal.
Overall peak LFP detection sufficient for aDBS stimulation occurred in 91.5% of patients while off medications and 84.8% while on medications, regardless of disease severity, the data showed.
Similar LFP detection rates were observed between those who received stimulation to the subthalamic nucleus (78%) or the globus pallidus internus (100%).
“Detection of an LFP signal may be sufficient for aDBS programming in the large majority of patients without necessitating medication withdrawal,” the researchers wrote.
Trial findings expected to support worldwide regulatory submissions
As part of the trial, the participants were randomly assigned to receive a single or dual threshold mode and then were switched between the two modes.
In single mode, when an LFP signal level crosses a threshold, adaptive DBS provides electrical stimulation until the LFP drops below the threshold, like on or off. This mode uses fast millisecond stimulation rates in response to LFPs to provide a method for rapid adaptation during high LFPs associated with low medication states and/or worsening motor symptoms.
In dual mode, stimulation is increased when LFPs surpass a threshold. Unlike in single mode, when LFPs fall below this threshold, the stimulation continues until the signals further decrease and cross a second, lower threshold. This mode uses a minute-to-minute timescale, which may optimally adjust to the time it takes for medications to work and help mitigate motor fluctuations, according to researchers.
As an example, the team reported LFP signals during aDBS delivery in a patient with implants in the subthalamic nucleus to confirm the adaptation of stimulation during task performance.
The difference in therapy delivery between single and dual-threshold modes was observable. In single mode, adjusted aDBS stimulation occurred over 250 milliseconds between the clinician’s upper and lower stimulation limits. In contrast, the dual threshold mode adjusted stimulation more slowly, and each adjustment was incremental rather than ramping up and down between the threshold limits, like in single mode.
Readings over 24 hours also were presented. A clear circadian rhythm — the body’s internal biological clock — was observed, in which LFP signals and aDBS stimulation were lower at night than during the day, when LFP tended to be higher. The two aDBS modes generally differed between night and day, with more stable stimulation in the dual threshold mode at night.
Medtronic stated that it has filed for regulatory approval of adaptive DBS in the U.S. According to the company, the findings of the ADAPT-PD trial are expected to support further regulatory submissions worldwide.
“For more than three decades, Medtronic’s investment in DBS research has led to significant improvements in therapeutic treatment for movement disorders and epilepsy,” said Amaza Reitmeier, vice president and general manager of Medtronic Brain Modulation. “This first-of-its-kind trial is a significant step forward in our journey to bring sensing-enabled DBS enhancements to patients.”
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