Clinical Trial Summary
Freezing of gait (FoG) is a common and debilitating condition in Parkinson's Disease (PD)
patients. FoG is described as an episodic inability to walk, which often triggers falls,
hospitalization and is an important predictor of poor quality of life. As locomotor regions
degenerate in PD, gait automaticity is impaired. Patients compensate by increasing volitional
control of gait, however, this adaptation has been found to worsen FoG severity. We
hypothesize that increased cortical control of gait is maladaptive, and therapies to improve
gait automaticity will not be effective unless cortical control of gait is reduced. The
long-term goal of this project is to develop a therapeutic approach for FoG that
simultaneously reduces cortical control and increases automaticity of gait. The objective is
to determine the locomotor network abnormalities responsible for FoG and demonstrate how
neuromodulation and rehabilitation can modulate the network. The rationale of this study is
that increased connectivity between brainstem locomotor regions and cortical structures
represents increased cortical governance of gait, and it can be reversed by the proposed
intervention. We will accomplish this by combining a course of inhibitory rTMS (1Hz) to the
cortex (supplementary motor area) with a rehabilitation protocol designed to increase gait
automaticity (dual task training). We have designed a study that will carefully assess the
locomotor network of freezers with resting state functional, diffusion and interleaved
TMS/BOLD MRI studies, before and after intervention. Behavioral measures including gait
analysis, cognitive and motor assessments will also be conducted at baseline and post
treatment. The study aims to determine the effects of our intervention on the locomotor
network (assessed with imaging), as well as on FoG severity as quantified through multiple
markers obtained through gait analysis. At the conclusion of the study we expect to have
determined the network changes central to the pathophysiology of FoG, the effects of 1Hz rTMS
+ rehabilitation on this network, and on FoG severity.
The relevance of this study to public health is to develop a non-invasive effective
therapeutic option for one of the most debilitating and untreatable conditions affecting the
lives of one million Americans suffering from PD; freezing of gait.
Subjects meeting diagnostic criteria for PD and documented freezing of gait will be recruited
from the MUSC Movement Disorder Clinic by clinical staff. Subjects will undergo identical
imaging protocols before and after intervention. Subjects will undergo ten, 20 minute, dual
task training sessions immediately following each rTMS session. Subjects will be randomized
to either active rTMS + rehabilitation or rehabilitation alone at a 2:1 ratio (10 active: 5
control). The primary outcome measure will be dual task interference for turning.
