Clinical trial NCT03273270: Effects of Neuromodulation and Rehabilitation of the Locomotor Network in Freezing of Gait
Official title: Effects of Neuromodulation and Rehabilitation of the Locomotor Network in Freezing of Gait
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease With Freezing of Gait
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2017-09-06
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

Subjects meeting diagnostic criteria for PD and documented FoG

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Exclusion Criteria:

* Subjects with contraindications to MRI, or TMS (no history of seizures, no metal implants in head, no pregnancy) dementia, or inability to complete the walk 30 feet in the off state without assistance will be excluded.

Primary outcomes:
measure: Change in Functional Connectivity to the Supplementary Motor Area.
timeFrame: pre and post intervention (within one week of completion)
Secondary outcomes:
measure: Change in New Freezing of Gait Questionnaire
timeFrame: pre and post intervention (within one week of completion)
measure: Change in Dual Task Time to Turn Off
timeFrame: pre and post intervention (within one week of completion)
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Gonzalo Revuelta, DO
role: PRINCIPAL_INVESTIGATOR
References: