Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease: ADAPT-PD clinical trial methodology and early data
Helen Bronte-Stewart1, Martijn Beudel2, Jill L. Ostrem3, Alfonso Fasano4, Leonardo Almeida5, Travis Hassell6, Elena Moro7, Michal Gostkowski8, Kyle T. Mitchell9, Elodie Hainque10, Nagaraja Sarangmat11, Scott Stanslaski12, Lisa Tonder12, Rebekah Summers12, Robert S. Raike12, Todd M. Herrington13
1Neurology and Neurological Sciences, Stanford Neurology, 2Neurology, Amsterdam University Medical Centers, 3Neurology, University of California San Francisco, 4Krembil Brain Institute, University of Toronto Toronto, 5Neurology, Shands at University of Florida, University of Florida, 6Neurology, Vanderbilt University Medical Center, 7Grenoble Alpes University, CHU of Grenoble, 8Center for Neurological Restoration, Cleveland Clinic Foundation, 9Duke University Movement Disorders Center, Duke University, 10Département de Neurologie, Hôpital Pitie Salpetrière, APHP, Sorbonne Université, 11Oxford University Hospitals NHS Foundation Trust, 12Medtronic Neuromodulation, Medtronic, 13Massachusetts General Hospital, Harvard Medical School
Objective:
To describe the design and early data from the pivotal Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) clinical trial (NCT04547712).
Background:
In pilot studies, adaptive deep brain stimulation (aDBS) has been associated with greater motor symptom control, fewer side effects, and lower total electrical energy delivered (TEED) compared to continuous DBS (cDBS).
Design/Methods:
The ADAPT-PD study is a multicenter, prospective, single-blind, randomized crossover clinical investigation evaluating the safety and effectiveness of aDBS for Parkinson’s disease (PD). The study includes a cohort without (primary cohort) and with directional stimulation (directional cohort). Participants have globus pallidus pars interna or subthalamic nucleus DBS leads connected to a Medtronic PerceptTM PC DBS device capable of sensing local field potentials (LFPs). An investigational feature is unlocked to allow programming of two different aDBS modes using low frequency (8-30 Hz) LFP control signals. The study consists of four phases following enrollment: cDBS Baseline, aDBS Setup and Adjustment, aDBS Evaluation, and Long-term Follow-up. Randomized, single-blinded crossover to aDBS in a single or dual-threshold mode is executed in participants with an acceptable response to either or both aDBS modes.
Results:
The clinical trial is ongoing with 12 centers activated and 10 sites which have enrolled a primary cohort of 68 and a directional cohort of 17. Demographic and preliminary data will be featured at the time of presentation. Primary endpoint is the equivalence of aDBS to cDBS for ON time without troublesome dyskinesia. Other endpoints are TEED, motor assessments from a wearable device, Voice Handicap Index, MDS-UPDRS, EQ-5D-5L, PDSS-2, PDQ-39, and patient preference. Safety measures include stimulation-related adverse events (AEs), other AEs, and device deficiencies.
Conclusions:
This pivotal clinical study of aDBS in a clinical and home setting is expected to generate data to assess the safety and effectiveness for aDBS in PD.