PMID- 34980610 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20220429 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 12 IP - 1 DP - 2022 Jan 3 TI - 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. PG - e049955 LID - 10.1136/bmjopen-2021-049955 [doi] LID - e049955 AB - INTRODUCTION: After 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). METHODS: The 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 DISSEMINATION: The trial was approved as premarket study by the Italian, Polish, and Dutch Competent Authorities: Bioethics Committee at National Oncology Institute of Maria Sklodowska-Curie-National Research Institute in Warsaw; Comitato Etico Milano Area 2; Comitato Etico IRCCS Istituto Neurologico C. Besta; Comitato Etico interaziendale AOUC Citta della Salute e della Scienza-AO Ordine Mauriziano di Torino-ASL Citta di Torino; De Medisch Ethisch Toetsingscommissie van Maastricht UMC. The study started enrolling patients in January 2021. TRIAL REGISTRATION NUMBER: NCT04681534. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Marceglia, Sara AU - Marceglia S AUID- ORCID: 0000-0002-0456-866X AD - Dipartimento di Ingegneria e Architettura, Universita degli Studi di Trieste, Trieste, Italy smarceglia@units.it. AD - UO Neurofisiopatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Conti, Costanza AU - Conti C AD - Newronika SpA, Milan, Italy. FAU - Svanidze, Oleg AU - Svanidze O AD - Newronika SpA, Milan, Italy. FAU - Foffani, Guglielmo AU - Foffani G AD - Fundacion del Hospital Nacional de Paraplejicos para la Investigacion y la Integracion, Toledo, Spain. AD - CINAC, Hospital Universitario HM Puerta del Sur, Universidad CEU-San Pablo, Mostoles, Madrid, Spain. FAU - Lozano, Andres M AU - Lozano AM AD - Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. AD - Krembil Research Institute, University Health Network, Toronto, Ontario, Canada. FAU - Moro, Elena AU - Moro E AD - Grenoble Institute of Neurosciences, INSERM U1216, University Grenoble Alpes, Grenoble, France. FAU - Volkmann, Jens AU - Volkmann J AD - Department of Neurology, University of Wurzburg, Wurzburg, Germany. FAU - Arlotti, Mattia AU - Arlotti M AD - Newronika SpA, Milan, Italy. FAU - Rossi, Lorenzo AU - Rossi L AD - Newronika SpA, Milan, Italy. FAU - Priori, Alberto AU - Priori A AD - ASST Santi Paolo e Carlo, Milano, Italy. AD - Aldo Ravelli Research Center for Neurotechnology and Experimental Neurotherapeutics, Department of Health Sciences, University of Milan, Milan, Italy. LA - eng SI - ClinicalTrials.gov/NCT04681534 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220103 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 SB - IM MH - Adaptation, Physiological MH - *Deep Brain Stimulation/methods MH - Humans MH - *Parkinson Disease/diagnosis/therapy MH - Pilot Projects MH - Randomized Controlled Trials as Topic MH - *Subthalamic Nucleus PMC - PMC8724732 OTO - NOTNLM OT - *neurology OT - *parkinson-s disease OT - *protocols & guidelines COIS- Competing interests: All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Conflict of Interest statement: AP, GF and SM are founders and shareholders of Newronika SpA, and are member of Newronika's scientific advisory board. LR is founder, shareholder and CEO of Newronika SpA. MA and OS are stock option holder and work for Newronika S.p.A. CC works for Newronika SpA. EM is member of the scientific advisory board of Newronika SpA, JV is member of the scientific advisory board of Newronika SpA and works as a consultant to Boston Scientific and Medtronic, and has received honoraria for lectures from Boston Scientific and Medtronic as well as research grants from Boston Scientific and Medtronic, AML is member of the scientific advisory board of Newronika SpA, has served as a consultant for Boston Scientific, Medtronic, Aleva, and Abbott and is a cofounder of Functional Neuromodulation. EDAT- 2022/01/05 06:00 MHDA- 2022/03/16 06:00 PMCR- 2022/01/03 CRDT- 2022/01/04 06:00 PHST- 2022/01/04 06:00 [entrez] PHST- 2022/01/05 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2022/01/03 00:00 [pmc-release] AID - bmjopen-2021-049955 [pii] AID - 10.1136/bmjopen-2021-049955 [doi] PST - epublish SO - BMJ Open. 2022 Jan 3;12(1):e049955. doi: 10.1136/bmjopen-2021-049955.