Effects of Neuromodulation and Rehabilitation of the Locomotor Network in Freezing of Gait

NCT03273270 | Completed Results FDA Device

• 1 other identifier: TMS/FOG
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease With Freezing of Gait

Outcome Measures

Primary Outcomes (1)

• Change in Functional Connectivity to the Supplementary Motor Area.

  Change (pre vs post intervention) in resting-state fMRI connectivity (fisher z-score) of the supplemental motor area (SMA). A negative change score means there was a reduction in SMA connectivity pre to post intervention. A positive change score means there was an increase in SMA connectivity pre to post intervention.

  pre and post intervention (within one week of completion)

Secondary Outcomes (2)

• Change in New Freezing of Gait Questionnaire

  pre and post intervention (within one week of completion)

• Change in Dual Task Time to Turn Off

  pre and post intervention (within one week of completion)

Study Arms (2)

Active TMS

EXPERIMENTAL

1 Hz repetitive transcranial magnetic stimulation

Radiation: transcranial magnetic stimulation

Sham TMS

PLACEBO COMPARATOR

No active stimulation

Radiation: transcranial magnetic stimulation

Interventions

transcranial magnetic stimulation RADIATION

transcranial magnetic stimulation

Active TMS; Sham TMS

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects meeting diagnostic criteria for PD and documented FoG

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Interventions

Transcranial Magnetic Stimulation

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Limitations and Caveats

Multiple variables were collected with gait analysis (i.e. velocity, step length, time) however, we hypothesized dual task time to turn during the OFF conditions would be most likely to change pre to post intervention. In order to minimize multiple comparisons among gait measures dual task time to turn was selected as the most important variable to detect freezing since turning and dual tasking are common triggers.

Results Point of Contact

• Title: Gonzalo Revuelta
• Organization: Medical University of South Carolina

revuelta@musc.edu

7927262

Study Officials

• Gonzalo Revuelta, DO

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: September 6, 2017
• Study Start: July 31, 2017
• Primary Completion: March 23, 2020
• Study Completion: March 23, 2020
• Last Updated: March 29, 2021
• Results First Posted: March 29, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)