The RESSTORE project includes 9 tightly interconnected WPs as shown in the figure below:
WP1 aims at producing, controlling (identification, safety and functionality) and releasing the Adipose derived Mesenchymal Stem Cells (ADMSC), (Tissue Engineered Advanced Therapy Medicinal Products, EMA/CAT/600280/2010) according to a harmonized manufacturing process under GMP. Cell therapy units from Spain, Finland and France will produce, according to this defined manufacturing process, the ADMSC batches to be administrated to patients under WP2.
WP2 consists in the registration of the trial, the recruitment of the 400 patients, the conduction and monitoring of the clinical trial and the collection of blood samples (to be processed under WP3) and clinical data (centralised under WP4).
WP3 aims at i) establishing the RESSTORE Bio-bank which can enable the completion of advanced biomarker research, ii) defining the biological “proof of concept” of RESSTORE trial through the demonstration of modifications of candidate biomarkers related with growth factors, angiogenesis and brain damage biomarkers after stroke treatment with ADMSC and iii) developing a bedside test to biologically monitor stroke ADMSC therapy. A standardized multimodal MRI protocol used for patients’ data acquisition will also be designed: 1) DTI-derived measures such as fractional anisotropy; 2) functional brain connectivity measures, as biomarkers of motor recovery to assess the efficiency of cell therapy at 3 month follow-up; 3) mask delineation for MRI preprocessing and lesion volume measurement. MRI data will be centralised and analysed using the computing tools developed under WP6.
WP4 focuses on the management of the trial data (as part of WP2) to achieve an accurate and complete clinical trial database. It will include the setting up of i) the project database (database design) and electronic CRFs (eCRFs) allowing entry of the trial data into the database (eCRF design) as well as ii) the randomisation facility for the trial. This WP will also include the creation and maintenance of specific plans for managing the data (DMP, DVP and DDP). Data edit checks will be programmed and run against the trial data/logistics. Data listing and data derivation procedures will also be implemented.
WP5: Based on the centralised data originating from WP4, WP3 and WP7, WP5 is dedicated to i) the clinical trial statistical analysis, ii) data analysis and modelling (e.g. dimension reduction, latent variables modelling, simulations), iii) knowledge modelling, system biology, virtual population, effect model and simulations as well as iv) Health economics analysis and modelling.
WP6 is dedicated to the clinical MR Imaging programs (P-Locus, Diffusionist and graph theory analysis) development to be used under WP3.
WP7 aims at producing supporting data to the RESSTORE clinical trial. Specifically, this work package will i) assess the effect of intensive rehabilitation and co-morbid conditions on functional improvement induced by human ADMSCs in experimental stroke models and ii) explore neurobiological mechanisms underlying the therapeutic efficacy of human ADMSCs in stroke animals with or without comorbidities undergoing rehabilitation; and iii) assess safety of cell therapy.
WP8 consists in the development of the effective communication and dissemination strategy of RESSTORE as well as the operational communication, dissemination and valorisation of its findings and ethics monitoring.
Finally, WP9 focuses on the management of the overall project and its resources to ensure an efficient coordination and timely delivery of all outcomes through i) the establishment of procedures and reporting structures, ii) providing management time, administration, coordination functions, iii) the organisation of contractual and interim technical and financial progress reports, iv) the management of work package activities and deliverables against agreed milestones, and v) the implementation and dynamic monitoring of a global data management plan. Management is embedded within all the WPs, with identified partners assuming lead roles, supported by experienced supporting staff.