Mallory L Hacker1, James Tonascia2, Maxim Turchan3, Amanda Currie3, Lauren Heusinkveld3, Peter E Konrad4, Thomas L Davis3, Joseph S Neimat4, Fenna T Phibbs3, Peter Hedera3, Lily Wang5, Yaping Shi5, David M Shade2, Alice L Sternberg2, Lea T Drye2, David Charles3. 1. Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States. Electronic address: mallory.hacker@vanderbilt.edu. 2. Department of Epidemiology, Johns Hopkins University, 615 N Wolfe St., Baltimore, MD, 21205, United States. 3. Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States. 4. Department of Neurosurgery, Vanderbilt University, 4340 Village at Vanderbilt, Nashville, TN, 37232-8618, United States. 5. Department of Biostatistics, Vanderbilt University, 2525 West End Avenue, Suite 11000, Nashville, TN, 37212, United States.
Abstract
BACKGROUND: The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. METHODS: A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. RESULTS:DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, andPDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. CONCLUSIONS:DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD.
RCT Entities:
BACKGROUND: The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. METHODS: A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. RESULTS: DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. CONCLUSIONS: DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD.
Authors: Mallory L Hacker; Maxim Turchan; Lauren E Heusinkveld; Amanda D Currie; Sarah H Millan; Anna L Molinari; Peter E Konrad; Thomas L Davis; Fenna T Phibbs; Peter Hedera; Kevin R Cannard; Li Wang; David Charles Journal: Neurology Date: 2020-06-29 Impact factor: 11.800
Authors: Mallory L Hacker; Amanda D Currie; Anna L Molinari; Maxim Turchan; Sarah M Millan; Lauren E Heusinkveld; Jonathon Roach; Peter E Konrad; Thomas L Davis; Joseph S Neimat; Fenna T Phibbs; Peter Hedera; Daniel W Byrne; David Charles Journal: J Parkinsons Dis Date: 2016 Impact factor: 5.568
Authors: I Madrazo; O Kopyov; M A Ávila-Rodríguez; F Ostrosky; H Carrasco; A Kopyov; A Avendaño-Estrada; F Jiménez; E Magallón; C Zamorano; G González; T Valenzuela; R Carrillo; F Palma; R Rivera; R E Franco-Bourland; G Guízar-Sahagún Journal: Cell Transplant Date: 2018-12-21 Impact factor: 4.064
Authors: Andres M Lozano; Nir Lipsman; Hagai Bergman; Peter Brown; Stephan Chabardes; Jin Woo Chang; Keith Matthews; Cameron C McIntyre; Thomas E Schlaepfer; Michael Schulder; Yasin Temel; Jens Volkmann; Joachim K Krauss Journal: Nat Rev Neurol Date: 2019-03 Impact factor: 42.937