Investigating the Neural Signature of Freezing of Gait in Parkinson's Disease (FOG-EEG)

Investigating the Neural Signature of Freezing of Gait Using Ambulatory Electroencephalography in Parkinson's Disease

Freezing of Gait (FOG) is a disabling symptom of Parkinson's disease (PD) and a leading cause for falls. Current medical management is inadequate to alleviate FOG so there is need for improved treatments. A major draw-back in the development of better treatments for FOG is the difficulty in detecting episodes and our poor understanding of its underlying pathophysiology.

This study will investigate the cortical signature of FOG using ambulatory electroencephalography (EEG) to help improve FOG detection algorithms and provide novel insights into the underlying pathophysiology, which together will guide therapy development.

Study Overview

• Status: Enrolling by invitation
• Conditions: Parkinson Disease; Basal Ganglia Diseases; Movement Disorders; Freezing of Gait; Brain Disease; Neurodegenerative Disease

• Study Type: Observational
• Enrollment (Estimated): 28

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Department of Rehabilitation Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

People with Parkinson's Disease who self-report to experience FOG more than once a day.

Description

Inclusion Criteria:

1. Clinical diagnosis of Parkinson's disease (PD) made by a Neurologist*
2. Modified Hoehn & Yahr (H&Y) Stage I to IV in the ON medication state
3. Age above 18 years*
4. Able to walk 5 minutes while unassisted by a walker or another person (the use of a cane is allowed).*
5. Mini Mental State Examination>= 21
6. At least three hours in-between regular medication intakes to allow for stable testing time.*
7. Self-reported FOG with a severity of at least 1 FOG episode per day, based on items 1 and 2 of the New Freezing of Gait Questionnaire, irrespective of FOG occurring ON- or OFF-medication.*
8. Stable medication scheme for at least 7 days before enrollment.

Exclusion Criteria:

1. Participation in another clinical intervention study*
2. Acute musculoskeletal or other neurological, psychiatric, or cardiovascular conditions affecting gait or any other medical condition which, in the opinion of the investigator, may prevent the participant from completing the protocol in full
3. Unable to adhere to assessment procedures leading to missing or unusable data, as determined by the investigators
4. Not a stable medication scheme for at least 7 days before the assessment.*

5. Occurrence of any of the following within 3 months prior to informed consent:

   • Orthopedic surgery of the lower extremity
   • Myocardial infarction
   • Hospitalization for unstable angina
   • Coronary artery bypass graft
   • Percutaneous coronary intervention
   • Implantation of a cardiac resynchronization therapy device
   • Implantation of deep brain stimulation
6. Substance abuse that may interfere with the patient's compliance

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Home assessment; All 28 participants will undergo a single home based assessment including a gait protocol as well as administering clinimetrics and questionnaires. Patients will be tested early in the morning after at least 12 hours without the anti-parkinsonian medication (= 'partial' OFF medication) and then about 1 hour after the intake of the first morning medication dose, when the subject reports reaching self-reported ON state (= ON medication). The gait protocol consist out of A) a trajectory in the participants home from the living room towards the bathroom and back, including a 360° turn as well as a figure-8 turn and going through a doorway and B) a daily living task. All tests will be conducted in a fixed order. The protocol will be conducted as a single task, with a dual task (serial subtraction task), with voluntary stops during different parts of the trajectory, and with an auditory cue (rhythm set 10% slower then typical cadence).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Power spectral density (Watts/hertz) of beta frequencies	The averaged power spectral density (PSD) of the beta (12-25 Hz) frequency band measured over the motor cortices during freezing of gait (FOG) episodes compared to typical gait performance in the same individual with Parkinson's disease as measured during different walking trajectories in the home setting.	During walking protocol (duration 15-20 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Power spectral density (Watts/hertz) of theta frequencies bands	The averaged power spectral density (PSD) of the theta (4-7 Hz) frequency band measured over the prefrontal cortices during freezing of gait (FOG) episodes compared to typical gait performance in the same individual with Parkinson's disease as measured during different walking trajectories in the home setting.	During walking protocol (duration 15-20 minutes)
Cross-frequency coupling between beta and theta frequency bands	The averaged cross-frequency coupling (CFC) between the beta (12-25 Hz) and theta (4-7 Hz) frequency bands as measured over the motor and prefrontal cortices during freezing of gait (FOG) episodes compared to typical gait performance in the same individual with Parkinson's disease as measured during different walking trajectories in the home setting.	During walking protocol (duration 15-20 minutes)
Power spectral density (Watts/hertz) and cross-frequency coupling (CFC) of beta and theta frequencies bands over other cortical areas.	The averaged power spectral density (PSD) of the beta (12-25 Hz) and theta (4-7 Hz) frequency band measured over other cortical areas (prefrontal, motor, temporal, parietal, visual) during freezing of gait (FOG) episodes compared to typical gait performance in the same individual with Parkinson's disease as measured during different walking trajectories in the home setting.	During walking protocol (duration 15-20 minutes)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Power spectrum density and cross-frequency coupling in ON medication state	Comparing the PSD/CFC of the primary and secondary outcomes averaged across all FOG episodes to typical gait performance during optimal ON medication state (1 hour post-medication intake)	During walking protocol (duration 15-20 minutes)
Power spectrum density and cross-frequency coupling in OFF medication state	Comparing the PSD/CFC of the primary and secondary outcomes averaged across all FOG episodes to typical gait performance during the practically defined OFF medication state (after minimal 12 hours overnight withdrawal).	During walking protocol (duration 15-20 minutes)
Comparing the Power spectrum density and cross-frequency coupling in ON and OFF medication state	Comparing the PSD/CFC averaged across all FOG episodes compared to typical gait performance between OFF and ON medication states	During walking protocol (duration 15-20 minutes)
Comparing the Power spectrum density and cross-frequency coupling between different FOG manifestations	Comparing the averaged PSD/CFC between the different FOG manifestations (Akinetic vs. Kinetic FOG trembling vs. Kinetic non-trembling vs. Kinetic-festination) in the ON and OFF medication states.	During walking protocol (duration 15-20 minutes)

Collaborators and Investigators

• Sponsor: KU Leuven
• Investigators: Principal Investigator: Moran Gilat, PhD, KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 27, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's Disease; freezing of gait; electroencephalography (EEG); gait problems
• Additional Relevant MeSH Terms: Synucleinopathies; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Movement Disorders; Parkinson Disease; Brain Diseases; Neurodegenerative Diseases; Basal Ganglia Diseases
• Other Study ID Numbers: s69013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The datasets could be made available under restricted access after publication of the results, following ethical approval and a data-transfer agreement. GDPR and privacy regulations will be adhered to.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No