Imaging Biomarkers of FOG Response to DBS

NCT06951906 | Recruiting Phase 4 FDA Device

• 2 other identifiers: Pro001314101R01NS131396-01A1
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Freezing of Gait; Parkinson's Disease; Deep Brain Stimulation

Outcome Measures

Primary Outcomes (4)

• Turn Duration

  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.

  Assessed at Baseline (Visit 3) and at 12 months post-activation (Visit 7)

• Difference in BOLD Response to STN-DBS

  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

  Assessed post-operatively at 6 months (Visit 5) and 12 months (Visit 6).

• Difference in Structural Connectivity

  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.

  Based on baseline diffusion MRI data (Visit 4) and analyzed in relation to DBS response determined at 12 months post-activation.

• Difference in Structural Integrity

  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.

  Based on baseline diffusion MRI data (Visit 4) and analyzed in relation to DBS response determined at 12 months post-activation.

Study Arms (1)

PD Patients with FOG undergoing DBS

ACTIVE COMPARATOR

Diagnostic Test: fMRI

Interventions

fMRI DIAGNOSTIC_TEST

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.

PD Patients with FOG undergoing DBS

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>40 years of age.
• diagnosis of PD based on UK Brain Bank diagnostic criteria.
• 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).
• clinically selected at the MUSC DBS Conference to undergo STN-DBS surgery.

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Related Publications (1)

• 1. Forsaa EB, Larsen JP, Wentzel-Larsen T, Alves G. A 12-year population-based study of freezing of gait in Parkinson's disease. Parkinsonism Relat Disord 2015; 21(3): 254-8. 2. Perez-Lloret S, Negre-Pages L, Damier P, et al. Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease. JAMA Neurol 2014; 71(7): 884-90. 3. Nieuwboer A, Giladi N. Characterizing freezing of gait in Parkinson's disease: Models of an episodic phenomenon. Mov Disord 2013; 28(11): 1509-19. 4. Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol 2011; 10(8): 734-44. 5. Moore O, Peretz C, Giladi N. Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait. Mov Disord 2007; 22(15): 2192-5. 6. Grimbergen YA, Munneke M, Bloem BR. Falls in Parkinson's disease. Curr Opin Neurol 2004; 17(4): 405-15. 7. Walton CC, Shine JM, Hall JM, et al. The major impact of freezing of gait on quality of life in Parkinson's disease. J Neurol 2015; 262(1): 108-15. 8. Barbe MT, Tonder L, Krack P, et al. Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease With Early Motor Complications. Mov Disord 2020; 35(1): 82-90. 9. Defer GL, Widner H, Marie RM, Remy P, Levivier M. Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord 1999; 14(4): 572-84. 10. Artusi CA, Lopiano L, Morgante F. Deep Brain Stimulation Selection Criteria for Parkinson's Disease: Time to Go beyond CAPSIT-PD. J Clin Med 2020; 9(12). 11. Charles PD, Van Blercom N, Krack P, et al. Predictors of effective bilateral subthalamic nucleus stimulation for PD. Neurology 2002; 59(6): 932-4. 12. Welter ML, Houeto JL, Tezenas du Montcel S, et al. Clinical predictive factors of subthalamic stimulation in Parkinson's disease. Brain 2002; 125(Pt 3): 575-83. 13. Schlenstedt C, Shalash A, Muthuraman M, Fal

  BACKGROUND

Related Links

• Investigating Gait with NeuroImaging \& Neuromodulation

MeSH Terms

Conditions

Parkinson Disease

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: April 30, 2025
• Study Start: November 11, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)