Etiology-Phenotype-Outcome Pathway Study on Freezing of Gait (FOG)

FREEZE-Path Cohort: Etiology-Phenotype-Outcome Pathway Study on Freezing of Gait (FOG)

This study is a prospective, multicenter, observational cohort (patient registry) designed to better understand freezing of gait (FOG), a disabling walking problem that can occur in Parkinson's disease and other related neurological conditions.The purpose of this registry is to collect long-term clinical information from patients with freezing of gait or gait and balance problems, and to explore how different causes of FOG are related to symptoms, walking patterns, falls, disease progression, and outcomes over time. The study will include participants with Parkinson's disease and other conditions associated with freezing of gait.Participants will receive standard medical care as determined by their treating physicians. No experimental drugs or study-related treatments will be assigned as part of this registry. Clinical information will be collected during routine visits and follow-up assessments, including questionnaires, walking and balance evaluations, video recordings, and other commonly used clinical tests.The information collected in this study may help improve the understanding of freezing of gait, support better risk assessment for falls, and guide future research and clinical management strategies for patients with gait and balance disorders.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease; Parkinsonism; Freezing of Gait; Vascular Parkinsonism; Idiopathic Normal Pressure Hydrocephalus (INPH)
• Intervention / Treatment: Other: Observational Data Collection

Detailed Description

Freezing of gait (FOG) is a common and disabling gait disturbance characterized by a transient inability to initiate or maintain effective stepping. It is most frequently observed in Parkinson's disease but can also occur in other parkinsonian syndromes and neurological conditions associated with gait and balance dysfunction. Freezing of gait is associated with falls, loss of independence, reduced quality of life, and increased caregiver burden, yet its underlying mechanisms, clinical heterogeneity, and long-term trajectories remain incompletely understood.

This study is a prospective, multicenter, observational patient registry designed to systematically collect longitudinal clinical data from adults with freezing of gait, gait and balance impairment, or those at high risk for developing freezing of gait. Participants will be recruited from neurology and related specialty clinics at participating centers and followed over time as part of routine clinical care.

The registry will collect a broad range of clinical information, including but not limited to:

Demographic and clinical characteristics; Freezing of gait severity and related symptoms; Objective gait parameters and balance performance assessed using standardized gait tasks; Motor symptom severity and functional status; Falls and fall-related outcomes; Health-related quality of life and other patient-reported outcomes. Clinical assessments will be performed at baseline and during scheduled follow-up visits over a planned follow-up period of up to 36 months. Data collection may include questionnaires, clinician-rated scales, objective gait and balance assessments, and video-based evaluations, depending on local clinical practice and participant capability.

This registry is non-interventional. All diagnostic and therapeutic decisions, including medication adjustments and rehabilitative interventions, will be made solely by the treating physicians according to standard clinical practice. The study does not mandate any experimental drugs, devices, or procedures.

The primary objectives of this registry are to:

Characterize the longitudinal course and clinical variability of freezing of gait; Examine associations between freezing of gait, gait and balance impairment, falls, and clinical outcomes; Identify potential clinical phenotypes and risk factors associated with worsening gait dysfunction and adverse outcomes.

The findings from this registry are intended to support hypothesis generation, improve clinical risk assessment, and provide a foundation for the development of future mechanistic studies and interventional trials targeting freezing of gait and related gait disorders.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Peipei Liu, MD; Phone Number: 86-13512204476; Email: pddoctorpipi2021@163.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300350
      • Recruiting
      • Tianjin Huanhu Hospital
      • Contact: Peipei Liu, MD; Phone Number: 86-13512204476; Email: pddoctorpipi2021@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population includes adults aged 30 to 85 years with freezing of gait or gait and balance impairment. Participants are diagnosed with Parkinson's disease or other parkinsonian or related neurological disorders associated with freezing of gait, including but not limited to parkinsonian syndromes and other causes of gait dysfunction.

Both participants with established freezing of gait and participants at high risk for developing freezing of gait are included. All participants are recruited from neurology and related specialty clinics at participating centers and are followed longitudinally as part of a prospective observational patient registry.

Description

Inclusion Criteria:

1. Age 30-85 years
2. Presence of freezing of gait or non-freezing gait or balance impairment
3. Diagnosis of Parkinson's disease or related parkinsonian disorders according to established international criteria (including PD, PSP, MSA, DLB, CBD, vascular parkinsonism, or idiopathic normal pressure hydrocephalus)
4. Ability to complete gait and balance assessment tasks independently or with assistance
5. Ability and willingness to provide written informed consent

Exclusion Criteria:

1. Severe dementia (Mini-Mental State Examination score < 10)
2. Severe psychiatric disorders interfering with study participation
3. Severe cardiopulmonary, musculoskeletal, or other medical conditions significantly affecting gait safety
4. Stroke, fracture, or other major medical events within the past 3 months
5. Inability to comply with follow-up procedures
6. Refusal of video or speech data collection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FOG Group; This cohort includes participants with freezing of gait present at baseline. Participants may have Parkinson's disease or other neurological conditions associated with freezing of gait. All participants receive standard clinical care as determined by their treating physicians. No experimental treatments or study-specific interventions are assigned as part of this observational registry.	Other: Observational Data Collection; This is an observational patient registry. No experimental drugs, devices, or procedures are assigned as part of the study. All participants receive standard medical care, and data are collected during routine clinical visits and follow-up assessments.
High-Risk Group; This cohort includes participants with gait or balance impairment who have not developed freezing of gait at baseline but are considered at high risk for future freezing of gait. Participants may have Parkinson's disease or related neurological disorders. All participants receive standard clinical care, and no experimental treatments or study-specific interventions are provided as part of this observational registry.	Other: Observational Data Collection; This is an observational patient registry. No experimental drugs, devices, or procedures are assigned as part of the study. All participants receive standard medical care, and data are collected during routine clinical visits and follow-up assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Freezing of Gait Severity Measured by the New Freezing of Gait Questionnaire (NFOG-Q)	The New Freezing of Gait Questionnaire (NFOG-Q) is a patient-reported outcome measure assessing the severity and impact of freezing of gait in Parkinson's disease. The total score ranges from 0 to 28, with higher scores indicating more severe freezing of gait. The primary outcome is the change in NFOG-Q total score from baseline to 36 months.	Baseline to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Freezing of Gait Event	Time from baseline to the first occurrence of freezing of gait in participants without freezing of gait at baseline.	Baseline to 36 months
Frequency of Falls	Number of falls reported during follow-up, collected through clinical visits and follow-up assessments.	Baseline to 36 months
Change in Health-Related Quality of Life Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39)	Health-related quality of life will be assessed using the Parkinson's Disease Questionnaire-39 (PDQ-39), a validated patient-reported outcome measure for individuals with Parkinson's disease. The PDQ-39 Summary Index score ranges from 0 to 100, with higher scores indicating worse health-related quality of life. The outcome is defined as the change in PDQ-39 Summary Index score from baseline to 36 months.	Baseline to 36 months
Change in Gait Speed	Gait speed will be measured during standardized gait tasks using an objective gait assessment system. The outcome is defined as the change in gait speed (meters per second, m/s) from baseline to 36 months, with higher values indicating better gait performance.	Baseline to 36 months
Change in Stride Length	Stride length will be assessed during standardized gait tasks using an objective gait assessment system. The outcome is defined as the change in stride length (meters, m) from baseline to 36 months, with higher values indicating better gait performance.	Baseline to 36 months
Change in Gait Variability	Gait variability will be quantified during standardized gait tasks using an objective gait assessment system. Gait variability will be expressed as the coefficient of variation (%) of stride length. The outcome is defined as the change in gait variability from baseline to 36 months, with lower values indicating better gait stability.	Baseline to 36 months
Change in Balance Performance Measured by the Mini-Balance Evaluation Systems Test (Mini-BESTest)	Balance performance will be assessed using the Mini-Balance Evaluation Systems Test (Mini-BESTest), a validated clinical scale for evaluating dynamic balance in patients with Parkinson's disease. The Mini-BESTest total score ranges from 0 to 28, with higher scores indicating better balance performance. The outcome is defined as the change in Mini-BESTest total score from baseline to 36 months.	Baseline to 36 months
Changes in functional brain network connectivity assessed by resting-state functional MRI (fMRI)	This outcome evaluates longitudinal changes in fMRI-derived functional connectivity within and between frontal cortical regions, basal ganglia, and brainstem locomotor control areas. The objective is to construct an integrated "brain network-clinical phenotype-FOG outcome" framework, enabling identification of neural network signatures specifically associated with freezing of gait and its progression.	Baseline to 36 months.

Collaborators and Investigators

• Sponsor: Tianjin Huanhu Hospital
• Investigators: Principal Investigator: Peipei Liu, MD, Tianjin Huanhu Hospital

Publications and helpful links

General Publications

• 1.Talia H, Yael B, Michal B, et al.: A meta-analysis identifies factors predicting the future development of freezing of gait in parkinson's disease[J]. NPJ Parkinsons Dis 2023, 9.10.1038/s41531-023-00600-2. 2.Richard C, Meg E M, Frederico P-F, et al.: Prevention of falls in parkinson's disease: Guidelines and gaps[J]. Mov Disord Clin Pract 2023, 10.10.1002/mdc3.13860. 3.Seira T, Yuta K, Takanori K, et al.: New insights into freezing of gait in parkinson's disease from spectral dynamic causal modeling[J]. Mov Disord 2024, 39.10.1002/mds.29988. 4.Giladi N, Nieuwboer A. Understanding and treating freezing of gait in Parkinson's disease: a review of current concepts and future directions. Lancet Neurology. 2008;7(8):720-730. 5.Kelvin L C, Prabesh K, Miriam vEB, et al.: Cholinergic system changes in dopa-unresponsive freezing of gait in parkinson's disease[J]. Mov Disord 2025, 40.10.1002/mds.30196.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): November 30, 2030

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson's Disease; parkinsonism; Freezing of Gait
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Parkinson Disease; Parkinsonian Disorders
• Other Study ID Numbers: (Jin Huan) 2025-297

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No