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

  • JAMA Neurol. 2025 Nov 1;82(11):1171-1180. doi: 10.1001/jamaneurol.2025.2781.
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
Affiliations
  • 1. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Standford, California.
  • 2. Department of Neurology, Amsterdam University Medical Centers, Amsterdam, Netherlands.
  • 3. Department of Neurology, University of California San Francisco.
  • 4. Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville.
  • 5. Department of Neurology, University of Minnesota, Minneapolis.
  • 6. Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • 7. Krembil Brain Institute, University of Toronto, Toronto, Ontario, Canada.
  • 8. Department of Neurology, Vanderbilt University Medical Center, Nashville.
  • 9. Duke University Movement Disorders Center, Duke University, Durham.
  • 10. Grenoble Alpes University, Division of Neurology, Centre Hospitalier Universitaire of Grenoble, Grenoble Institute of Neuroscience, Grenoble, France.
  • 11. Center for Neurological Restoration, Cleveland Clinic Foundation, Cleveland.
  • 12. Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
  • 13. Department of Neurosurgery, University of California, San Francisco.
  • 14. Department of Neurology, University of Pennsylvania, Philadelphia.
  • 15. Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia.
  • 16. Department of Neurosurgery, Shands at University of Florida, University of Florida, Gainesville.
  • 17. Massachusetts General Hospital, Harvard Medical School, Boston.
  • 18. Department of Internal Medicine, Faculty of Medicine, Yarmouk University, Irbid, Jordan.
  • 19. Medtronic Neuromodulation, Medtronic, Minneapolis, Minnesota.
PMID: 40982287 DOI: 10.1001/jamaneurol.2025.2781
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.