One million Americans live with Parkinson's disease (PD), a progressive neurodegenerative disease characterized by cardinal motor features that include tremor, bradykinesia, rigidity, and postural instability. Patients often battle the disease for 20 years or more, and investigations are needed to identify therapies that provide improved long-term benefits. Subthalamic nucleus (STN) deep brain stimulation (DBS) is an FDA- approved adjunctive therapy that improves motor function and quality of life and reduces motor fluctuations and dyskinesias in mid- and advanced-stage PD. The benefits of DBS in advanced stage PD have been reported in prospectively followed cohorts up to 10 years, and this long-term clinical success of DBS in later stages of PD motivates investigations to determine whether earlier intervention could extend or even enhance its benefits. Vanderbilt University completed the first prospective, randomized, controlled pilot clinical trial evaluating bilateral STN-DBS in early stage PD (IDE G050016, NCT 0282152, CRC 1363, IRB 040797). That safety and tolerability study provided the preliminary data to support the FDA's approval of a future pivotal trial to test the hypothesis that early DBS is superior to the current standard of care (IDE G050016). Since joining the trial as early stage patients, the pilot trial cohort has now progressed 10 years to a stage where motor and cognitive symptoms are increasingly resistant to medications. Understanding the durability of DBS therapy becomes even more critical when considering its application in early PD due to the added length of time patients will have the device implanted. Therefore, this study seeks to conduct a longitudinal follow-up visit in patients who completed the only prospective, randomized, controlled pilot clinical trial of DBS in early stage PD [early optimal drug therapy (ODT) n=11; early DBS+ODT n=12].
Aim 1 will analyze 10-year changes in motor and cognitive outcomes in subjects who completed the DBS in early PD pilot trial. Additionally, metabolic brain networks have been identified using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) that correlate with Parkinson's disease motor and cognitive symptom progression.
Aim 2 will utilize FDG-PET imaging during a therapeutic washout to explore whether long-term DBS applied in early disease modulates underlying PD metabolic network expression. Exploratory aims will evaluate 10-year changes in quality of life, activities of daily living, and antiparkinsonian medications and the development of dyskinesia or other motor complications. Results of this study will be an important contribution to the Parkinson's disease community, because this will be the first report of long-term clinical outcomes of early DBS, including the only data available concerning its longevity for managing motor symptoms, its long-term impact on cognition, and its influence on the development of motor complications or dyskinesia. These results will further inform the design of the FDA-approved safety and efficacy trial of DBS in early stage PD and also generate new hypotheses to be tested in sub-studies within the multicenter trial as well as in future prospective investigations.
Parkinson's disease (PD) patients often battle the neurodegenerative disease for 20 years or more, and improved long-term treatment options are needed. This research project will be the first to address questions concerning the durability of subthalamic nucleus (STN) deep brain stimulation (DBS) when applied in early stage Parkinson's disease. This work will also be the first to use positron electron tomography (PET) imaging to explore whether PD-related metabolic brain networks are influenced by long-term DBS first applied in early stage Parkinson's disease.
