Imaging Biomarkers of FOG Response to DBS

Recruiting

• Conditions: Freezing of Gait Symptoms in Parkinson's Disease; Deep Brain Stimulation

• Registration Number: NCT06951906
• Lead Sponsor: Medical University of South Carolina

Brief Summary

For this study, the investigators are recruiting 54 individuals with Parkinson's Disease and Freezing of Gait (FOG) who are planning to undergo Deep Brain Stimulation (DBS). The objective of this study is to better understand the FOG response to DBS. Prior to DBS, participants will undergo an MRI scan, behavioral assessment related to walking, a cognitive evaluation, and assessment of other Parkinson's disease symptoms. Following DBS, participants will repeat these assessments at multiple timepoints over the period of one year. Overall, participants will complete a total of 7 visits over a period of approximately 1 year.

Detailed Description

The long-term goal of this research is to develop an individualized approach for the treatment of Freezing of Gait (FOG) with Deep Brain Stimulation (DBS). In pursuit of this goal, the investigators have preliminary findings which show that:

1. Effective subthalamic nucleus DBS (STN-DBS) activates the globus pallidus interna (GPi) and decreases cortical activation in Parkinson's Disease (PD);

2. Structural connectivity to the GPi, supplemental motor area (SMA), and primary motor cortex (M1) is associated with DBS response in FOG; and

3. Decreased microstructural integrity of the GPi is associated with decreased DOPA response in FOG.

The investigators propose a conceptual framework whereby engaging a specific FOG response network depends on the structural integrity of the network, as well as lead placement and stimulation parameters. The investigators propose to recruit 54 individuals with FOG who are identified as appropriate STN-DBS candidates to undergo a prospective longitudinal imaging and behavioral study of FOG response to STN-DBS. Baseline behavioral assessments will characterize FOG behavior, severity, subtype, as well as the cognitive profile, non-FOG motor severity, and other demographics of the enrolled participants that may contribute to DBS response. Baseline imaging will utilize advanced diffusion MRI metrics to determine which brain areas are structurally connected to the stimulation target and their structural integrity. Post-operative assessments will include behavioral measures of FOG response and imaging measures of neural response to stimulation. Pre- and post-operative data will be used to evaluate the association between structural integrity, connectivity, and behavioral response.

Study Timeline

• Study Start: 2024-11-11
• Study First Submitted: 2025-04-23
• Study First Submitted QC: 2025-04-23
• Study First Posted: 2025-04-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11
• Primary Completion: 2029-11
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

1. >40 years of age.
2. diagnosis of PD based on UK Brain Bank diagnostic criteria.
3. presence of FOG, defined as a score of 1 on part 1 of the nFOGQ and confirmed by objective evaluation (a score of 1 represents a positive response of having experienced such an episode over the last month).
4. clinically selected at the MUSC DBS Conference to undergo STN-DBS surgery.

Exclusion Criteria

1. a history of other significant gait impairment unrelated to PD (e.g. orthopedic deformities).
2. inability to complete gait assessments (timed-up-and-go task) in the OFF state without assistance or assist devices.
3. contraindications to MRI, including inability to lie supine in the scanner environment, pregnancy, and non-MRI compatible metal implants.
4. implantation of non-3 T MRI-compatible DBS devices.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Turn Duration	Assessed at Baseline (Visit 3) and at 12 months post-activation (Visit 7)	Turn duration is measured during the timed up and go (TUG) task. Subjects are instrumented with inertial measurement units (IMUs), and turn duration is measured from the first step onto a marked box to the last toe off the box during the turn.
Difference in BOLD Response to STN-DBS	Assessed post-operatively at 6 months (Visit 5) and 12 months (Visit 6).	Whole-brain activation is assessed via BOLD signal changes associated with T2\*-relaxation rate during combined Deep Brain Stimulation and functional MRI (DBS-fMRI). This involves cycling the DBS device ON and OFF during resting-state scans
Difference in Structural Connectivity	Based on baseline diffusion MRI data (Visit 4) and analyzed in relation to DBS response determined at 12 months post-activation.	Structural connectivity profiles are determined using individual structural connectivity data and the Volume of Tissue Activated (VTA) model, which accounts for stimulation settings and lead placement. The outcome is the comparison of VTA connectivity to specific brain regions (e.g., GPi, SMA, M1, GPe) between STN-DBS responsive and unresponsive participants.
Difference in Structural Integrity	Based on baseline diffusion MRI data (Visit 4) and analyzed in relation to DBS response determined at 12 months post-activation.	Microstructural integrity of brain structures (e.g., STN, GPi, PPN) is assessed using advanced diffusion MRI metrics, specifically Diffusional Kurtosis Imaging (DKI). The outcome is the comparison of these metrics between STN-DBS responsive and unresponsive participants.

Trial Locations

Locations (1)

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States