NCT05370105

Brief Summary

The combination of rehabilitation protocols and regenerative therapies offers the outstanding opportunity to promote and enhance the endogenous regenerative and repair processes occurring in tissues damaged or lost due to injury, disease, or age. Still, one of the main hurdles in the clinical approach to regenerative rehabilitation is the lack of easily accessible and sensitive biomarkers for the evaluation of rehabilitation and therapy efficacy. Extracellular vesicles (EVs) are nanoscaled vesicles that mediate intercellular communication among organs. EVs were shown to be involved in the onset, progression and resolution of many disorders, being also used as valuable tool in the regenerative medicine field. However, the initial enthusiastic approach to EVs has been hindered in its transfer to clinics because of technological obstacles related to their dimensions and to their limited amount. The present project proposes the application of a Surface Plasmon Resonance imaging (SPRi)-based biosensor for the detection and characterization of blood EVs from stroke patients, before and after rehabilitation. After the successful SPRi detection of EVs of different cellular origin (brain and non-brain cells), the quantification of specific surface molecules related to pathological or regeneration processes will be accomplished. If successful, the project will 1) demonstrate the ability of the SPRi biosensor to reveal differences in the relative amount of specific cell-derived EV subpopulations and in their cargo during disease progression and rehabilitation induced recovery, 2) provide support for using the proposed SPRi-based biosensor for the detection and characterization of circulating EVs in order to evaluate the efficacy of rehabilitation protocols and regenerative therapies, 3) identify new biomarkers for the profiling of stroke patients to personalize the rehabilitation therapies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
88

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jun 2018

Longer than P75 for all trials

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 25, 2018

Completed
3.7 years until next milestone

First Submitted

Initial submission to the registry

March 22, 2022

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 11, 2022

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2022

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2023

Completed
Last Updated

February 3, 2025

Status Verified

January 1, 2025

Enrollment Period

4.3 years

First QC Date

March 22, 2022

Last Update Submit

January 30, 2025

Conditions

StrokeRehabilitation

Keywords

brain remodelingextracellular vesiclesbiosensorbiophotonicsrehabilitation markersregenerationneuroinflammationstroke biomarkers

Outcome Measures

Primary Outcomes (1)

  • Change in modified Barthel index after rehabilitation

    modified Barthel index (Shah et al., 1989)

    01/11/2020 - 30/03/2022

Secondary Outcomes (11)

  • Extracellular vesicles characterization by SPRi

    25/06/2018 - 30/09/2022

  • Change in Numeric Rating Scale (NRS) PAIN or PAINAD for non-verbal patient after rehabilitation

    25/06/2018 - 30/09/2022

  • Change in anamnestic and current modified RANKIN scale after rehabilitation

    25/06/2018 - 30/09/2022

  • Change in NIH-STROKE SCALE after rehabilitation

    25/06/2018 - 30/09/2022

  • Change in Fugl-Meyer Assessment (FMA) scale after rehabilitation

    25/06/2018 - 30/09/2022

  • +6 more secondary outcomes

Study Arms (2)

Stroke patients

80 post-stroke patients will be asked to undergo three samples of biological material (10 ml of blood): the first collection on the second day of hospitalization at IRCCS S. Maria Nascente (Milano) or at IRCCS Don Gnocchi (Florence) of Fondazioen Don Gnocchi (t0) and a second withdrawal at discharge (t1), or approximately 2 months after the first withdrawal. Where possible, a third sampling (t2 - follow up) will be performed 6 months after the event.

Other: blood withdrawal

Healthy Controls

The healthy controls will be volunteers recruited at Fondazione Don Gnocchi, who are not affected by neurodegenerative and cardiovascular diseases and who have not taken anti-inflammatory drugs in the week prior to recruitment.

Other: blood withdrawal

Interventions

blood withdrawalOTHER

10 ml of blood, two 5 ml tubes suitable for serum isolation. Given the nature and objectives of the study, there are no risks and / o inconveniences of particular importance for the patient since the blood samples will be performed according to the common procedure used in all analysis laboratories. At the end of the collection, in the area where the blood sample was taken, a small bruise may form which will disappear in the following hours, in any case during the collection particular attention will be paid to the subjects being treated with antiplatelet and anticoagulants. The study does not include the execution of interventional treatments or therapies.

Healthy ControlsStroke patients

Eligibility Criteria

Age35 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients hospitalized at Fondazione Don Gnocchi after stroke injury and undergoing an intensive rehabilitation program.

You may qualify if:

  • Diagnosis of ischemic or haemorrhagic stroke related to intensive post-stroke rehabilitation hospitalization
  • within 15 days of the ictal event

You may not qualify if:

  • Previous head injuries/traumas
  • Oncological diseases
  • Diseases of the immune and haematological system
  • Neurodegenerative diseases

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

IRCCS Don Gnocchi, Fondazione Don Carlo Gnocchi ONLUS

Florence, Italy

Location

IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi ONLUS

Milan, 20148, Italy

Location

Related Publications (6)

  • Picciolini S, Gualerzi A, Vanna R, Sguassero A, Gramatica F, Bedoni M, Masserini M, Morasso C. Detection and Characterization of Different Brain-Derived Subpopulations of Plasma Exosomes by Surface Plasmon Resonance Imaging. Anal Chem. 2018 Aug 7;90(15):8873-8880. doi: 10.1021/acs.analchem.8b00941. Epub 2018 Jul 17.

    PMID: 29972017BACKGROUND

  • Gualerzi A, Picciolini S, Carlomagno C, Terenzi F, Ramat S, Sorbi S, Bedoni M. Raman profiling of circulating extracellular vesicles for the stratification of Parkinson's patients. Nanomedicine. 2019 Nov;22:102097. doi: 10.1016/j.nano.2019.102097. Epub 2019 Oct 21.

    PMID: 31648040BACKGROUND

  • Picciolini S, Gualerzi A, Carlomagno C, Cabinio M, Sorrentino S, Baglio F, Bedoni M. An SPRi-based biosensor pilot study: Analysis of multiple circulating extracellular vesicles and hippocampal volume in Alzheimer's disease. J Pharm Biomed Anal. 2021 Jan 5;192:113649. doi: 10.1016/j.jpba.2020.113649. Epub 2020 Sep 23.

    PMID: 33038641BACKGROUND

  • Gualerzi A, Picciolini S, Carlomagno C, Roda F, Bedoni M. Biophotonics for diagnostic detection of extracellular vesicles. Adv Drug Deliv Rev. 2021 Jul;174:229-249. doi: 10.1016/j.addr.2021.04.014. Epub 2021 Apr 19.

    PMID: 33887403BACKGROUND

  • Gualerzi A, Picciolini S, Roda F, Bedoni M. Extracellular Vesicles in Regeneration and Rehabilitation Recovery after Stroke. Biology (Basel). 2021 Aug 30;10(9):843. doi: 10.3390/biology10090843.

    PMID: 34571720BACKGROUND

  • Picciolini S, Mangolini V, Roda F, Montesano A, Arnaboldi F, Liuzzi P, Mannini A, Bedoni M, Gualerzi A. Multiplexing Biosensor for the Detection of Extracellular Vesicles as Biomarkers of Tissue Damage and Recovery after Ischemic Stroke. Int J Mol Sci. 2023 Apr 27;24(9):7937. doi: 10.3390/ijms24097937.

    PMID: 37175644RESULT

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Serum samples used for extracellular vesicles isolation. DNA content will be not considered

MeSH Terms

Conditions

StrokeNeuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Alice Gualerzi, PhD

    Fondazione Don Carlo Gnocchi, Laboratory of Nanomedicine and Clinical Biophotonics

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 22, 2022

First Posted

May 11, 2022

Study Start

June 25, 2018

Primary Completion

September 30, 2022

Study Completion

July 31, 2023

Last Updated

February 3, 2025

Record last verified: 2025-01

Locations

IT(2)