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. 2025 Sep 22:e252781.
doi: 10.1001/jamaneurol.2025.2781. Online ahead of print.

Long-Term Personalized Adaptive Deep Brain Stimulation in Parkinson Disease: A Nonrandomized Clinical Trial

Helen M Bronte-Stewart  1 , Martijn Beudel  2 , Jill L Ostrem  3 , Simon Little  3 , Leonardo Almeida  4   5 , Adolfo Ramirez-Zamora  4 , Alfonso Fasano  6   7 , Travis Hassell  8 , Kyle T Mitchell  9 , Elena Moro  10 , Michal Gostkowski  11 , Gaurav Chattree  1 , Rob M A de Bie  2 , Martijn de Neeling  2 , Dan Piña-Fuentes  2 , Bart Swinnen  2   12 , Philip A Starr  13 , Lauren H Hammer  3   14   15 , Kelly D Foote  16 , R Mark Richardson  17 , Alice Flaherty  17 , Alexandra Boogers  6 , Qais Sa'di  6   18 , Sara Meoni  10 , Anna Castrioto  10 , Scott Stanslaski  19 , Rebekah L S Summers  19 , Lisa Tonder  19 , Ye Tan  19 , Helen Berrier  19 , Tim J Goble  19 , Robert S Raike  19 , Todd M Herrington  17 ; ADAPT-PD Investigators
Collaborators, Affiliations

Long-Term Personalized Adaptive Deep Brain Stimulation in Parkinson Disease: A Nonrandomized Clinical Trial

Helen M Bronte-Stewart et al. JAMA Neurol. .

Abstract

Importance: Adaptive deep brain stimulation (aDBS) automatically adjusts stimulation amplitude in response to changes in relevant neural activity in people with Parkinson disease (PD). Whether long-term at-home aDBS is safe and delivers effective therapy in people with PD remains unknown.

Objective: To determine the tolerability, efficacy, and safety of long-term aDBS in people with PD who were previously stable receiving continuous DBS (cDBS).

Design, setting, and participants: This international, open-label, prospective, pivotal trial enrolled participants from December 2020 to July 2022 in the US, Canada, and Europe. Referred participants with PD were first assessed while receiving stable cDBS and those who tolerated 2 aDBS modes were randomized and blinded to 30 days in each mode (single-blind crossover design); those who tolerated only 1 mode were assessed in that mode only; assessments completed holding medication stable. Participants were given the option to continue their selected mode of aDBS for long-term follow-up (10 months). Data used for analysis were from March 2024. Multiple imputation was used if more than 5% of data was missing for the primary or secondary end points. A referred sample of 68 participants with PD, stable while receiving cDBS and medication, was included.

Interventions: Two modes of aDBS controlled by an embedded closed-loop stimulation system: single threshold (ST-aDBS) and dual threshold (DT-aDBS).

Main outcomes and measures: The primary end point required that at least 50% of participants meet a performance goal of on-time (ie, time when symptoms were well controlled) without troublesome dyskinesias with no less than 1-SD reduction (and post hoc threshold less than 2 hours per day reduction) reported during aDBS therapy compared to cDBS, determined from a self-reported motor diary. The secondary end point was total electrical energy delivered (TEED) compared between aDBS and cDBS. Safety assessments were conducted by characterizing adverse events (AEs), stimulation-related AEs, serious AEs, and device deficiencies.

Results: A total of 68 participants enrolled (mean [SD] age, 62.2 [8.4] years; 48 [70.6%] male); 40 and 35 were evaluated with DT-aDBS and ST-aDBS, respectively. The primary end point performance goal was met in the DT-aDBS group (91% of participants) and ST-aDBS (79% of participants) with the post hoc performance threshold; no difference between aDBS modes (χ21 = 1.0; P = .51). TEED was reduced during ST-aDBS compared to cDBS (mean change, -15%; nominal P = .01) and not different from DT-aDBS. All but 1 stimulation-related AE resolved during the aDBS setup and adjustment phase with no serious device AEs through long-term follow-up. Exploratory analyses suggested improvement in on-time without troublesome dyskinesias with DT-aDBS compared to cDBS.

Conclusions and relevance: In this study, long-term aDBS was tolerable, effective, and safe in people with PD who were previously stable while receiving cDBS.

Trial registration: ClinicalTrials.gov Identifier: NCT04547712.

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Conflict of interest statement

Conflict of Interest Disclosures: All investigators and their institutions received sponsorship for the conduct of the ADAPT-PD clinical trial from Medtronic. Dr Bronte-Stewart reported grants from Medtronic the study during the conduct of the study. Dr Beudel reported research funding from the Amsterdam University Medical Center, the European Union Joint Programme–Neurodegenerative Disease Research project (2021), and stichting ParkinsonFonds (2023) and Medtronic (2023, 2024). Dr Ostrem reported grants from Medtronic to conduct study activities during the conduct of the study as well as grants from Neuroderm, Boston Scientific, Merz, Amneal, AbbVie, and Acadia and personal fees from Supernus, Highland Instruments, Larimar, Aspen, Acure X, and Insightec outside the submitted work. Dr Little reported personal fees from Iota Biosciences Consultancy outside the submitted work; in addition, Dr Little had a provisional patent for SF-2024-226-1-US issued on cortical-based adaptive deep brain stimulation. Dr Almeida reported consulting for Medtronic outside the submitted work. Dr Ramirez-Zamora reported grants from Medtronic and honoraria for educational activities during the conduct of the study as well as honoraria for educational activities from Boston Scientific and consulting fees from Iota Inc and AbbVie outside the submitted work. Dr Fasano reported grants and personal fees from Medtronic during the conduct of the study as well as personal fees from Abbott and Boston Scientific and grants from Boston Scientific outside the submitted work. Dr Hassell reported grants from Medtronic (support for clinical trial expenses as well as appropriate equipment to run the trial, such as study deep brain stimulation programmers and watches) during the conduct of the study as well as personal fees from Medtronic (consulting fees for advisory board service) outside the submitted work. Dr Mitchell reported grants from Medtronic (research support paid to institution during the conduct of the study) as well as consulting fees from Medtronic and Boston Scientific and grants from Surgical Information Sciences and Boston Scientific (research support paid to institution) outside the submitted work. Dr Moro reported financial support from Medtronic for the clinical trial during the conduct of the study as well as consulting honoraria from Medtronic and grants from France Parkinson, Abbott, and Universite Grenoble Alpes outside the submitted work. Dr Chattree reported personal fees from Medtronic outside the submitted work. Dr de Bie reported grants from Medtronic (paid to institution) during the conduct of the study. Dr de Neeling reported grants from Medtronic during the conduct of the study. Dr Starr reported educational grants from Medtronic and Boston Scientific as well as consulting fees from InBrain Neuroelectronics. Dr Hammer reported grants from Medtronic during the conduct of the study as well as consulting fees from Medtronic and Parkinson’s Foundation outside the submitted work; in addition, Dr Hammer had a patent for SF20242261US issued. Dr Richardson reported grants from Medtronic outside the submitted work. Dr Flaherty reported grants from Medtronic during the conduct of the study. Dr Boogers reported grants from Medtronic during the conduct of the study as well as personal fees from American Academy of Neurology and Abbott; nonfinancial support from Boston Scientific and Medtronic; and grants from Fernard Lazard Foundation outside the submitted work. Dr Castrioto reported grants (paid to the institution) from Medtronic for an unrelated study. Dr Stanslaski reported employment and shareholding at Medtronic; in addition, Dr Stanslaski had a patent for US10864368B2 issued. Dr Summers reported employment at Medtronic during the conduct of the study and outside the submitted work; in addition, Dr Summers had a patent for A0012338US01 pending. Mrs Tonder reported employment at Medtronic outside the submitted work. Dr Tan reported employment at Medtronic during the conduct of the study. Mrs Berrier reported personal fees from Medtronic during the conduct of the study and outside the submitted work. Dr Goble reported employment at and stock ownership in Medtronic. Dr Raike reported employment at Medtronic; in addition, Dr Raike had various neurotechnology patents issued. Dr Herrington reported grants and personal fees from Medtronic during the conduct of the study; MarvelBiome, Bayer, and Asklepios Biopharmaceutical outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram of Study
Study phases varied in duration: continuous deep brain stimulation (cDBS) baseline phase (approximately 30 days, up to 90 days), adaptive DBS (aDBS) setup and adjustment phase (up to 60 days), evaluation phase (approximately 30 days per mode), long-term follow-up phase (approximately 10 months), extended access phase (through commercial approval of the adaptive feature). DT indicates dual threshold; LFP, local field potential; ST, single threshold.
Figure 2.
Figure 2.. Changes in Motor Diary
A and B show the raw data for change in on-time (ie, time when symptoms were well controlled) without troublesome dyskinesia for each adaptive deep brain stimulation (aDBS) mode assessed compared to continuous DBS (cDBS) evaluation during single-threshold (ST) and dual-threshold (DT) modes. Filled datapoints indicate if the participant chose that mode at the long-term follow-up, unfilled dots indicate if the patient chose a different mode at the long-term follow-up. The prespecified performance threshold (−1 SD, dotted line) and post hoc threshold (−2 hours per day, dashed line) were used to determine success or failure to calculate the primary end point. C and D show the motor diary data evaluated during ST and DT as observed mean hours per day spent asleep, off-time (ie, time when symptoms were poorly controlled), and on-time with and without troublesome dyskinesia.
See this image and copyright information in PMC

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