Double-blind cross-over pilot trial protocol to evaluate the safety and preliminary efficacy of long-term adaptive deep brain stimulation in patients with Parkinson’s disease

Abstract

IntroductionAfter several years of brain-sensing technology development and proof-of-concept studies, adaptive deep brain stimulation (aDBS) is ready to better treat Parkinson’s disease (PD) using aDBS-capable implantable pulse generators (IPGs). New aDBS devices are capable of continuous sensing of neuronal activity from the subthalamic nucleus (STN) and contemporaneous stimulation automatically adapted to match the patient’s clinical state estimated from the analysis of STN activity using proprietary algorithms. Specific studies are necessary to assess superiority of aDBS vs conventional DBS (cDBS) therapy. This protocol describes an original innovative multicentre international study aimed to assess safety and efficacy of aDBS vs cDBS using a new generation of DBS IPG in PD (AlphaDBS system by Newronika SpA, Milan, Italy).MethodsThe study involves six investigational sites (in Italy, Poland and The Netherlands). The primary objective will be to evaluate the safety and tolerability of the AlphaDBS System, when used in cDBS and aDBS mode. Secondary objective will be to evaluate the potential efficacy of aDBS. After eligibility screening, 15 patients with PD already implanted with DBS systems and in need of battery replacement will be randomised to enter a two-phase protocol, including a ‘short-term follow-up’ (2 days experimental sessions during hospitalisation, 1 day per each mode) and a ‘long-term follow-up’ (1 month at home, 15 days per each mode).Ethics and disseminationThe trial was approved as premarket study by the Italian, Polish, and Dutch Competent Authorities: Bioethics Committee at National Oncology Institute of Maria Skłodowska-Curie—National Research Institute in Warsaw; Comitato Etico Milano Area 2; Comitato Etico IRCCS Istituto Neurologico C. Besta; Comitato Etico interaziendale AOUC Città della Salute e della Scienza—AO Ordine Mauriziano di Torino—ASL Città di Torino; De Medisch Ethisch Toetsingscommissie van Maastricht UMC. The study started enrolling patients in January 2021.Trial registration numberNCT04681534.

Personalized chronic adaptive deep brain stimulation outperforms conventional stimulation in Parkinson’s disease

“…This suggests individuals with PD could further benefit from aDBS. STN local field potential oscillations in a predefined beta band (13–30 Hz) are often proposed for adaptive (closed-loop) control in PD 2 , 17 , 18 based on the observation that resting subthalamic beta activity is elevated in the rigid/akinetic state and reduced when motor signs are alleviated by dopaminergic medication 19 or neurostimulation 20 . However, previous studies identified STN beta oscillations as control signals in the absence of stimulation.…”

Proceedings of the 10th annual deep brain stimulation think tank: Advances in cutting edge technologies, artificial intelligence, neuromodulation, neuroethics, interventional psychiatry, and women in neuromodulation

“…The AlphaDBS system features advanced filtering technology for detecting local field potentials (LFPs) sensed through the DBS lead ( Arlotti et al, 2021 ; Marceglia et al, 2022 ). The implanted stimulator also utilizes a linear control algorithm that adjusts stimulation parameters according to the power in a selectable frequency band of LFPs.…”

The Fifth Bioelectronic Medicine Summit: today’s tools, tomorrow’s therapies

“…Dr. Rossi spoke about Newronika’s efforts in developing a closed-loop system for deep brain stimulation (DBS). He described both the capabilities of the device to records brain signals during stimulation delivery from the same DBS electrodes, that include the digital signal processing steps enabling adjustments of stimulation parameters in real-time (Marceglia et al 2022 ).…”