The MOTIVE-PSP Initiative (Progressive Supranuclear Palsy)

Progressive Supranuclear Palsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04691635
• Other study ID #: CEMAND-2020-02
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: January 2025

Study information

• Verified date: January 2022
• Source: University of Salerno
• Contact: Marina Picillo, MD
• Phone: 00393497725402
• Email: mpicillo[@]unisa.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 165
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Progressive Supranuclear Palsy
• Supranuclear Palsy, Progressive

Intervention

Other:
• evaluation of movements with sensors
evaluation of movements with sensors

Locations

Country	Name	City	State
Italy	AOU Padova	Padova
Italy	AOU Pisa	Pisa
Italy	AOU San Giovanni di Dio e Ruggi d'Aragona	Salerno

Sponsors (3)

Lead Sponsor	Collaborator
University of Salerno	Azienda Ospedaliera di Padova, Azienda Ospedaliero, Universitaria Pisana

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Picillo M, Abate F, Ponticorvo S, Tepedino MF, Erro R, Frosini D, Del Prete E, Cecchi P, Cosottini M, Ceravolo R, Salle GD, Salle FD, Esposito F, Pellecchia MT, Manara R, Barone P. Association of MRI Measures With Disease Severity and Progression in Progressive Supranuclear Palsy. Front Neurol. 2020 Nov 12;11:603161. doi: 10.3389/fneur.2020.603161. eCollection 2020. — View Citation

Picillo M, Cuoco S, Amboni M, Bonifacio FP, Bruno A, Bruschi F, Cappiello A, De Micco R, De Rosa A, Di Biasio F, Elifani F, Erro R, Fabbri M, Falla M, Franco G, Frosini D, Galantucci S, Lazzeri G, Magistrelli L, Malaguti MC, Milner AV, Minafra B, Olivola E, Pilotto A, Rascunà C, Rizzetti MC, Schirinzi T, Borroni B, Ceravolo R, Di Fonzo A, Lopiano L, Marchese R, Mercuri NB, Modugno N, Nicoletti A, Padovani A, Santangelo G, Stefani A, Tessitore A, Volontè MA, Zangaglia R, Zappia M, Barone P. Validation of the Italian version of carers' quality-of-life questionnaire for parkinsonism (PQoL Carer) in progressive supranuclear palsy. Neurol Sci. 2019 Oct;40(10):2163-2169. doi: 10.1007/s10072-019-03944-x. Epub 2019 Jun 12. — View Citation

Picillo M, Cuoco S, Amboni M, Bonifacio FP, Bruschi F, Carotenuto I, De Micco R, De Rosa A, Del Prete E, Di Biasio F, Elifani F, Erro R, Fabbri M, Falla M, Franco G, Frosini D, Galantucci S, Lazzeri G, Magistrelli L, Malaguti MC, Milner AV, Minafra B, Olivola E, Pilotto A, Rascunà C, Rizzetti MC, Schirinzi T, Borroni B, Ceravolo R, Di Fonzo A, Marchese R, Mercuri NB, Modugno N, Nicoletti A, Padovani A, Santangelo G, Stefani A, Tessitore A, Volontè MA, Zangaglia R, Zappia M, Zibetti M, Barone P. Validation of the Italian version of the PSP Quality of Life questionnaire. Neurol Sci. 2019 Dec;40(12):2587-2594. doi: 10.1007/s10072-019-04010-2. Epub 2019 Jul 26. — View Citation

Picillo M, Cuoco S, Carotenuto I, Abate F, Erro R, Volpe G, Pellecchia MT, Catricalà E, Cappa S, Barone P. Clinical use of SAND battery to evaluate language in patients with Progressive Supranuclear Palsy. PLoS One. 2019 Oct 11;14(10):e0223621. doi: 10.1371/journal.pone.0223621. eCollection 2019. — View Citation

Picillo M, Cuoco S, Tepedino MF, Cappiello A, Volpe G, Erro R, Santangelo G, Pellecchia MT, Barone P; PSP Salerno study group. Motor, cognitive and behavioral differences in MDS PSP phenotypes. J Neurol. 2019 Jul;266(7):1727-1735. doi: 10.1007/s00415-019-09324-x. Epub 2019 Apr 15. — View Citation

Picillo M, Erro R, Cuoco S, Tepedino MF, Manara R, Pellecchia MT, Barone P; PSP Salerno Study Group. MDS PSP criteria in real-life clinical setting: Motor and cognitive characterization of subtypes. Mov Disord. 2018 Aug;33(8):1361-1365. doi: 10.1002/mds.27408. Epub 2018 Jul 8. — View Citation

Picillo M, Tepedino MF, Abate F, Erro R, Ponticorvo S, Tartaglione S, Volpe G, Frosini D, Cecchi P, Cosottini M, Ceravolo R, Esposito F, Pellecchia MT, Barone P, Manara R. Midbrain MRI assessments in progressive supranuclear palsy subtypes. J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):98-103. doi: 10.1136/jnnp-2019-321354. Epub 2019 Sep 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progressive Supranuclear Palsy rating scale	Progression of disease as assessed with the standard clinical scale rating (scoring 0-100, higher scores indicate worse scores) Progressive Supranuclear Palsy symptoms and signs	1-year follow up
Secondary	Cognitive progression	Evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale score (scoring 0-100, higher scores indicate better scores)	1-year follow up
Secondary	Behavioral progression	Behavioral symptoms as assessed with Neuropsychiatric Inventory scale (scoring 0-144, higher scores indicate worse scores)	1-year follow up
Secondary	MRI	Progression of disease as assessed with MRI specific measures (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)	1-year follow up
Secondary	Gait speed	Gait speed as assessed with motion sensors	1-year follow up