Progression of Striatal and Extrastriatal Degeneration in PD and PSP Patients (PARKONTHEWAY)

Progression of Striatal and Extrastriatal Degeneration in PD and PSP Patients: a Longitudinal Prospective Study for Correlation Between Clinical Manifestations, Gait Analysis and Functional/Diffusion MRI

This longitudinal study aims to research cognitive and gait phenotypes of Parkinson's disease and Supranuclear Palsy as well as to provide markers to track diseases progression using a multi-modality approach based on 3D-gait analysis and MR Imaging.

Specifically, this study want to identify cognitive pattern and gait-related cerebral diffusion/functional connectivity in PD and PSP patients and to verify their progression over a period of 18 months.

In summary, the current protocol proposed to investigate the following issues:

• to perform a multifactorial quantitative analysis of outcomes for PD and PSP compared to a control group in order to categorize cognitive and gait pattern in the group of patients and verify if the gait can be useful as discriminator for diagnosis.
• to analyze whether diffusion and resting-state functional connectivity indices are correlated with clinical disease severity scores and motor scores and how they change over time (18 months later).

Study Overview

• Status: Completed
• Conditions: Parkinson Disease (PD); Paralysis; Supranuclear
• Intervention / Treatment: Diagnostic test: 3D gait analysis; Diagnostic test: rsfMRI; Diagnostic test: Montreal Cognitive assesment (MoCA)

Detailed Description

Gait disorder is one of the key features of Parkinson's disease (PD), often leading to loss of mobility and severe disability. Yet in the early stages of disease, examination of gait may lead to inconclusive results for differential diagnosis between PD and other parkinsonism because slow and small stepped walking is often unspecific and can be related to age, depressive mood, or to a presence of neurodegenerative atypical parkinsonism (AP) such as Progressive Supranuclear Palsy (PSP).

At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single and dual-task testing.

It is therefore crucial to carefully investigate the multiple cognitive domains in order to identify possible mild cognitive deficits in PD and PSP patients and to correlate them with gait disorders.

The use of quantitative movement analysis with 3D-gait analysis allow an objective multifactorial evaluation of the functional limitation related to PD and PSP patients and can be used to analyze the gait in pathologies characterized by gait impairment compared to healthy control (HC).

This longitudinal clinical study aims to analyze cognitive profiles and gait pattern (with 3D-gait analysis) and their progression (18 months later) in a PD- and a PSP-group, respect to HC group.

Moreover, with the Magnetic Resonance Imaging (MRI), the study want to research for possible gait-related cerebral diffusion/functional connectivity alterations and their changes over time.

The specific aims of the project are:

• To perform a multifactorial quantitative analysis of outcomes for PD and PSP compared to a control group in order to categorize the gait in the group of patients and verify if the gait can be useful as discriminator for diagnosis.
• To detect possible cognitive deficits in Parkinson's Disease and PSP more corelated with gait disturbances.
• To analyze whether diffusion and resting-state functional connectivity indices are correlated with clinical disease severity scores and motor scores and how they change over time (18 months later).
• To identify gait-related cerebral diffusion/functional connectivity in PD and PSP patients and to verify their progression over a period of 18 months.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Frosinone
    • Cassino, Frosinone, Italy
      • Casa di cura San Raffaele Cassino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosis of idiopathic PD by United Kingdom (UK) Brain Bank criteria and PSP according to NINDS-SPSP criteria, without other significant neurological or orthopedic problems;
• ages of 20-80;
• able to walk 25 feet unassisted and without any assistive device

Exclusion Criteria:

• History of epileptic seizures, head injury, other neurological disorders.
• Cardiac pacemaker implantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PD patients: Parkinson's disease group; Diagnosis of idiopathic PD by United Kingdom Brain Bank criteria, exclusion of other significant neurological or orthopedic problems; ages of 21-90; able to walk 25 feet unassisted and without any assistive device. Imaging: rsfMRI, diffusion tensor imaging; Motor evaluation: 3D gait analysis; Movement Disorder Society (MDS)-UPDRS Behavioral: PD-MCI-specific Level II battery (Mov Dis. 2015 Mar; 30(3): 402-406)	Diagnostic test: 3D gait analysis; Computed analysis of posture and gait pattern and motor performance by kinematic and kinetics parameters analysis such as the step length, gait velocity, stride time variability, 3D joint kinematics, ground reaction forces, joint kinetics; Diagnostic test: rsfMRI; MR scans acquired by 1.5 Tesla (Siemens Medical Systems, Erlangen, Germany).; Other Names: resting state functional magnetic resonance (rsfMRI); Diagnostic test: Montreal Cognitive assesment (MoCA); Standard clinical questionnaire
Active Comparator: PSP patients; Application of the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy (NINDS-SPSP) criteria for the clinical diagnosis of "probable" PSP, evaluation of PSP rating scale, exclusion of other significant neurological or orthopedic problems; ages of 21-90; able to walk 25 feet unassisted and without any assistive device. Imaging: rsfMRI, diffusion tensor imaging; Motor evaluation: 3D gait analysis;MDS-UPDRS Behavioral: PD-MCI-specific Level II battery (Mov Dis. 2015 Mar; 30(3): 402-406)	Diagnostic test: 3D gait analysis; Computed analysis of posture and gait pattern and motor performance by kinematic and kinetics parameters analysis such as the step length, gait velocity, stride time variability, 3D joint kinematics, ground reaction forces, joint kinetics; Diagnostic test: rsfMRI; MR scans acquired by 1.5 Tesla (Siemens Medical Systems, Erlangen, Germany).; Other Names: resting state functional magnetic resonance (rsfMRI); Diagnostic test: Montreal Cognitive assesment (MoCA); Standard clinical questionnaire
Active Comparator: HC: healthy control group; Healthy adults ages 21-90 without movement disorders, psychiatric disorders, or dementia. Imaging: rsfMRI, diffusion tensor imaging; Motor evaluation: 3D gait analysis; Behavioral: PD-Mild Cognitive Impairment (MCI)-specific Level II battery (Mov Dis. 2015 Mar; 30(3): 402-406)	Diagnostic test: 3D gait analysis; Computed analysis of posture and gait pattern and motor performance by kinematic and kinetics parameters analysis such as the step length, gait velocity, stride time variability, 3D joint kinematics, ground reaction forces, joint kinetics; Diagnostic test: rsfMRI; MR scans acquired by 1.5 Tesla (Siemens Medical Systems, Erlangen, Germany).; Other Names: resting state functional magnetic resonance (rsfMRI); Diagnostic test: Montreal Cognitive assesment (MoCA); Standard clinical questionnaire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait profile Score (GPS) in PD and PSP patients	GPS quantifies the gait pattern deviation of the patient respect to normality range	18 months

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele Roma
• Investigators: Study Director: Fabrizio Stocchi, MD, PhD, IRCCS San Raffaele Pisana

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2015
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; 3D-gait analysis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Paralysis
• Other Study ID Numbers: RP 06/15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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