Freezing of Gait Symptoms in Parkinson's DiseasePhase 4NCT06951906
Imaging Biomarkers of FOG Response to DBS
A Phase 4 study testing fMRI in people with Freezing of Gait Symptoms in Parkinson's Disease and Deep Brain Stimulation, run by Medical University of South Carolina at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Freezing of Gait Symptoms in Parkinson's Disease, Deep Brain Stimulation
- What is being tested?
- fMRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Nov 2024to Jan 2030
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Niloufar Malakouti, M.D., 8437920235, malakout@musc.edu
Mahdi Sowlat, M.D., 8438766410, sowlat@musc.edu
About this study
Official title: Imaging Biomarkers of Freezing of Gait Response to Deep Brain Stimulation
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.
Read the 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:
- Effective subthalamic nucleus DBS (STN-DBS) activates the globus pallidus interna (GPi) and decreases cortical activation in Parkinson's Disease (PD);
- Structural connectivity to the GPi, supplemental motor area (SMA), and primary motor cortex (M1) is associated with DBS response in FOG; and
- 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.
- Being tested
- fMRI
- Keywords
- Freezing of Gait, Parkinson's Disease, Deep Brain Stimulation
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fMRIDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| PD Patients with FOG undergoing DBS | Active comparator | Not described Receives: Diagnostic Test: fMRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: Based on baseline diffusion MRI data (Visit 4) and analyzed in relation to DBS response determined at 12 months post-activation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2025
- Study start11 Nov 2024
- Primary completionNov 2029 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Freezing of Gait Symptoms in Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Gonzalo Revuelta, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06951906
- Sponsor's protocol ID
- Pro00131410
- Other IDs
- 1R01NS131396-01A1
- Status last verified
- Aug 2026
- First submitted
- 23 Apr 2025
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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