The MOTIVE-PSP Initiative

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Brief Title

The MOTIVE-PSP Initiative

Official Title

MotOr, cogniTIVe and Imaging charactErization of Progressive Supranuclear Palsy Phenotypes: a Longitudinal Prospective Study Looking for Biomarkers

Brief Summary

      Progressive Supranuclear Palsy (PSP) is a rapidly progressive neurodegenerative disease
      characterized by falls and oculomotor disturbances. Several clinical trials are currently
      evaluating the efficacy of new pharmacological compounds in slowing disease progression. Yet,
      both early diagnosis and evaluation of disease progression remain challenging.

      Study aims include verifying if specific motor, cognitive, language, cerebrospinal fluid and
      imaging assessments represent reliable biomarkers of PSP diagnosis, phenotypization and
      progression over 1-year follow up. Motor evaluation will include recordings from wearable
      sensors.

      Expected results include 1) improvement of PSP diagnosis and phenotypization; 2)improvement
      of evaluation of disease progression in the context of clinical trial; 3)enhancement of
      strategies to prevent falls and fractures in such patients leading, in turn, to significant
      cost savings for the National Health System.
    

Detailed Description

      Hyphotesis and Significance:

      1)Cross-sectional phase:verify if specific motor, cognitive, language, cerebrospinal fluid
      (CSF) and imaging assessments represent reliable biomarkers of diagnosis in PSP in the
      earliest stages of disease compared to Parkinson's disease (PD) and healthy controls (HC) and
      are able characterize the different PSP clinical phenotype 2)12-month longitudinal
      phase:verify if specific motor, cognitive, language, CSF and imaging assessments represent
      reliable biomarkers of disease progression also according to the clinical phenotype

      Preliminary Data:

      Cross-sectional data suggest that current motor, cognitive, language and imaging assessments
      may be useful in supporting the diagnosis of PSP compared to PD and HC, but not in
      characterizing the PSP clinical phenotypes. No robust data on wearable sensors and CSF
      biomarkers is available.

      Longitudinal data on such biomarkers are lacking. As for cognition, preliminary data suggest
      that the Repeatable Battery for the assessment of neuropsychological status (RBANS) may
      evaluate cognitive trajectories in PSP with Richardson's syndrome.

      Specific Aim 1:

      Determine the feasibility, validity and reliability of application of digital biomarkers in
      PSP. Specifically if clinic-based wearable sensors and smartphone-based remote assessments
      can (1) support early clinical diagnosis and phenotyping of PSP patients compared to PD and
      HC and (2) evaluate disease trajectories in the whole cohort of PSP patients and discrete
      phenotypes compared to standard rating scales.

      For both points the hypothesis is that both clinic-based and smartphone-based wearable
      sensors outperform standard rating scales.

      Specific aim 2:

      Verify if cognitive, language and behavioral testing can (1) support early clinical diagnosis
      and phenotyping of PSP patients compared to PD and HC and (2) evaluate disease trajectories
      in the whole cohort of PSP patients and discrete phenotypes.

      For point (1) the hypothesis is that cognitive, language and behavioral testing support early
      diagnosis and phenotyping in the earliest stages compared to PD and HC. For point (2) the
      hypothesis is that cognitive, language and behavioral testing are able to evaluate disease
      progression in the whole cohort of PSP patients and discrete phenotypes.

      Specific aim 3:

      Verify if single parameter and multiparameter magnetic resonance imaging (MRI) imaging
      assessments can (1) support early clinical diagnosis and phenotyping of PSP patients compared
      to PD and HC and (2) evaluate disease trajectories in the whole cohort of PSP patients and
      discrete phenotypes.

      Experimental design aim 1 includes a cross-sectional phase with enrollment of 3 groups of
      subjects (PSP, PD and HC).

      During the baseline evaluation each enrolled subject will perform:1) a clinic-based
      standardized protocol for assessment of gait with wearable inertial sensors to specifically
      monitor quality of gait and balance using a wide range of measures from the upper and lower
      body (APDM Mobility Lab system) ;2) home-based monitoring with smartphone of inertial
      measurement (balance and gait task) and voice recorded with microphone for at least 5 days;3)
      standard clinical rating scales including the PSP rating scale, the Natural History and
      Neuroprotection in Parkinson Plus Syndromes, Movement Disorder Society Unified Parkinson's
      disease rating scale part III, Falls diary to be filled during the 5-day home based
      monitoring. Caregivers will be asked to actively support patients for the home-
      smartphone-based digital biomarkers measurements.

      Furthermore, at baseline only PSP patients will be asked to perform lumbar puncture to
      collect CSF and measure total-tau, phosphorylated tau, Beta-amyloid 42, neurofilament light
      and heavy chain. A 12-month longitudinal phase will follow only for PSP patients.

      During both cross-sectional and longitudinal phases (every 3 months), only patients enrolled
      at Unit 1 will also perform a gait analysis assessment with a traditional opto-kinematic,
      hospital-based gait analysis system (Qualisys®, Sandvälen, Sweden).

      Experimental design aim 2 includes a cross-sectional phase with enrollment of 3 groups of
      subjects (PSP, PD and HC).

      During the baseline evaluation each enrolled subject will perform:1) the RBANS; 2)standard
      cognitive assessment currently used by part of the research team to evaluate cognitive
      abilities in PSP patients as detailed elsewhere; 3) functional autonomy will be evaluated
      with the Instrumental Activities of Daily Life, while depression and apathy with the Beck
      Depression Inventory II and Apathy Evaluation Scale, respectively; 4) other neuropsychiatric
      symptoms will be explored with the Neuropsychiatric Inventory; 5) language abilities will be
      explored with the Screening for Aphasia in NeuroDegeneration (SAND) battery.

      A 12-month longitudinal phase will follow only for PSP patients.

      Experimental design aim 3 includes a cross-sectional phase with enrollment of 3 groups of
      subjects (PSP, PD and HC).

      During the baseline evaluation each enrolled subject will undergo a multimodal 3T MRI. The
      MRI protocol will include conventional sequences for morphometric measures (ie, the superior
      cerebellar peduncles, the middle cerebellar peduncles, the MR Parkinsonism index, the
      midbrain-pons area ratio; a 3D Spoiled Gradient Recalled Echo (SPGR) and a 3D-GRE multi-echo
      susceptibility weighted (SWAN) images to obtain quantitative susceptibility mapping and ROI
      based measures in substantia nigra, basal ganglia thalamus, red nucleus and fronto-parietal
      cortex, a resting state functional MRI and an Arterial Spin Labeling sequence.

      A 12-month longitudinal phase will follow only for PSP patients. Both single parameter and
      multiparameter (morphometric, iron based, functional, and perfusion) MRI approaches will be
      applied to validate the usefulness of imaging assessments in predicting both early PSP
      diagnosis and phenotyping as well as disease progression.
    


Study Type

Observational


Primary Outcome

Progressive Supranuclear Palsy rating scale

Secondary Outcome

 Cognitive progression

Condition

Progressive Supranuclear Palsy

Intervention

evaluation of movements with sensors

Study Arms / Comparison Groups

 Group 1
Description:  Patients with Progressive Supranuclear Palsy

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

165

Start Date

September 2021

Completion Date

March 2024

Primary Completion Date

March 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of Progressive Supranuclear Palsy based on current available clinical
             criteria

          -  ability to walk for at least 5 steps

        Exclusion Criteria:

          -  Comorbidities interfering with study assessments

          -  Significant MRI abnormalities as cerebrovascular diseases, tumors.
      

Gender

All

Ages

40 Years - N/A


Contacts

, 00393497725402, [email protected]



Administrative Informations


NCT ID

NCT04691635

Organization ID

CEMAND-2020-02


Responsible Party

Principal Investigator

Study Sponsor

University of Salerno

Collaborators

 Azienda Ospedaliera di Padova

Study Sponsor

, , 


Verification Date

December 2020