Projects Portfolio

Projects that count on the collaboration of ItaCRIN

Full title: Autologous Adipose-Derived Mesenchymal Stromal Cells in the Treatment of Mild to Moderate Osteoarthritis
Summary: A phase IIb, prospective, multicentre, double-blind, triplearm, randomized versus placebo trial, to assess the efficacy of a single injection of either 2 or 10 x 106 autologous adipose derived mesenchymal stromal cells (ASC) in the treatment of mild to moderate osteoarthritis (OA) of the knee, active and unresponsive to conservative therapy for at least 12 months.
Links:

EU Clinical Trials Register, ClinicalTrials.gov

Full title: A multi-centre randomized, placebo-controlled trial of mirabegron, a new beta3-adrenergic receptor agonist on the progression of left ventricular mass and diastolic function in patients with structural heart disease
Summary: Prospective, randomized, placebo-controlled, multi-centric international phase IIb clinical trial. The target population consists of patients with cardiac structural remodelling with or without symptoms of heart failure (maximum NYHA II). The objective is to evaluate mirabegron (a new β3-specific agonist) over 12 months as add-on to standard treatment compared to standard treatment alone. Endpoints focus on cardiac remodelling: Quantitative indices of hypertrophy and left ventricle (LV) function, in addition exercise tolerance is investigated.
Links:

ClinicalTrials.gov

Full title: Clinical Trial for the Regeneration of Cartilage Lesions in the Knee (NosetoKnee2)
Summary: The purpose of this study is to investigate the efficacy of an engineered cartilage transplant (N-TEC) in comparison to a cell-activated matrix (N-CAM) for the treatment of articular cartilage lesions in the knee. The main innovations in this trial are the use of nasal chondrocytes and the implantation of a tissue in contrast to cells seeded on a matrix. The goals of the trial are to: (i) evaluate whether implantation of a more mature graft (tissue therapy) is beneficial for the quality and durability of the repair tissue and the clinical outcome, (ii) determine the potential of the mature graft to integrate with the adjacent cartilage and form hyaline repair tissue and (iii) assess the efficacy of each treatment in correlation to the characteristics of the defect (e.g. acute versus chronic setting).
Links:

ClinicalTrials.gov

Full title: Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke
Summary: This study evaluates the use of Colchicine in adults over 40 years of age who have suffered an ischaemic stroke or transient ischaemic attack NOT caused by cardiac embolism or other defined causes. Patients will be randomised to 0.5 mg/day of Colchicine plus usual care, or to usual care alone. To investigate the efficacy of low dose colchicine (0.5mg/day) plus usual care (defined as antiplatelet, lipid-lowering, antihypertensive treatment, and appropriate lifestyle advice) compared with usual care alone to prevent non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, hospitalization for unstable angina and vascular death after ischaemic stroke or transient ischaemic attack (TIA) not caused by cardiac embolism or other defined causes unrelated to atherosclerosis
Links:

ClinicalTrials.gov

Full title: Clinical Research Initiative for Global Health
Summary: The Clinical Research Initiative for Global Health (CRIGH) aims to support international collaboration on clinical research for the benefit of patients, healthcare professionals, and health systems. The initiative will seek to optimise clinical research programmes in participating countries, to develop global standards on clinical research, to promote the take-up of innovative methodology and technologies, and to enhance institutional capacity to rapidly and efficiently respond to global health challenges. Launched in 2016, CRIGH is a follow-up to the Organisation for Economic Co-operation and Development (OECD) Global Science Forum (GSF) initiative, introduced in 2009 to foster international cooperation in non-commercial trials. The GSF made various recommendations to address three main challenges to multi-country collaboration: persisting differences in administrative processes; inadequate regulation for some clinical trials; and uneven national and regional support for education, training and infrastructures for academic clinical trials. CRIGH is the first global initiative to address the wide range of obstacles to global cooperation in clinical research, facilitating both multi-country commercial and non-commercial trials. CRIGH includes six projects: Infrastructure and funding: developing a network of high-quality and interoperable clinical trial units (CTUs), and promoting additional funding for independent, international trials. Global core competencies: promoting harmonized education, training and careers for investigators and clinical research professionals. Research ethics: promoting quality, consistency and training among research ethics committees. Patient involvement: fostering the involvement of patients as trial participants and in trial design. Comparative effectiveness research and socio-economic impact: promoting methodologies for efficient comparison of treatment strategies, and assessing the medical, social and economic impact of evidence. Regulatory awareness: developing databases on ethical and regulatory requirements, and recommendations to facilitate international cooperation. CRIGH will primarily focus on investigator-initiated trials and trials involving small and medium enterprises (SMEs). The CRIGH consortium is composed of Members and Observers - research institutions or organisations, or consortia of research institutions. ECRIN shares the secretariat with the National Institutes of Health (NIH).
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Full title: Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease: Comparative Effectiveness Research of Existing Technologies
Summary: This is a pragmatic randomised controlled trial (PRCT) evaluating the superiority of CT over ICA concerning effectiveness in stable chest pain patients with intermediate pretest probability of coronary artery disease.
Links:

EU Community Research and Development Information Service (CORDIS), ClinicalTrials.gov

Full title: Providing an open collaborative space for digital biology in Europe
Summary: EOSC-Life brings together the 13 Biological and Medical ESFRI research infrastructures (BMS RIs) to create an open collaborative space for digital biology. It is our joint response to the challenge of analysing and reusing the prodigious amounts of data produced by life-science. Managing and integrating this data is beyond the capabilities of most individual end-users and institutes. By publishing data and tools in a Europe-wide cloud EOSC-Life aims to bring the capabilities of big science projects to the wider research community. Federated user access (AAI) will allow transnational resource access and authorisation. EOSC-Life establishes a novel access model for the BMS RI: through EOSC scientists would gain direct access to FAIR data and tools in a cloud environment available throughout the European Research Area. EOSC-Life will make BMS RIs data resources FAIR and publish them in the EOSC following guidelines and standards (e.g. EDMI). Overall this will drive the evolution of the RI repository infrastructure for EOSC and integration of the BMS RI repositories. EOSC-Life will implement workflows that cross disciplines and RI boundaries and address the needs of interdisciplinary science. Through open hackathons and bring-your-own-data events we will co-create EOSC-Life with our user communities , providing a blueprint for how the EOSC supports wide-spread and excellent data-driven life science research. EOSC-Life will address the data policies needed for human research data under GDPR. Interoperable provenance information describe history of sample and data to ensure reproducibility and adherence to regulatory requirements. The goal of the EOSC-Life project is to make sure that life-scientists can find, access and integrate life-science data for analysis and reuse in academic and industrial research. EOSC-Life will transform European life-science by providing an open, continent-scale, collaborative and interdisciplinary environment for data science.
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Full title: Hydroxycholoroquine in paediatric ILD_START randomized controlled in-parallel group, then switch to placebo active drug, and STOP randomized controlled in-parallel group to evaluate the efficacy and safety of hydroxychloroquine (HCQ)
Summary: The surfactant dysfunction disorders are an important group of molecularly and histologically defined entities, belonging to the interstitial lung diseases in children (chILD). Mutations in genes encoding for surfactant protein C, surfactant protein B, the lipid transporter ABCA3, thyroid transcription factor 1 and others, cause a significant group of phenotypically similar chronic interstitial lung diseases with high morbidity and early mortality. Unfortunately no successfully proven treatments are available. Beyond oxygen supplementation, nutritional support and immunizations, the small molecule hydroxychloroquine (HCQ) has been identified during decades of trial and error treatments for surfactant dysfunction disorders. Together with promising in vitro data, HCQ has the potential as an innovative lead compound for this group of diseases. During a previous FP7 project ending 2016 the highest priority for further study in clinical trials was assigned to HCQ due to greatest patients´ needs, wide off-label usage, the results of a worldwide Delphi process and direct recommendation from the Committee for Orphan Medicinal Products (COMP) members. As part of that project the most suitable study design was developed. This randomized phase 2b double blind clinical study of HCQ in patients with surfactant dysfunction disorders has a design which allows a flexible beginning, either the initiation or the withdrawal of HCQ. The primary objective is to investigate if HCQ improves the oxygenation compared to placebo in a group of 60 well defined subjects with surfactant dysfunction disorders. Secondary objectives of the project will generate important knowledge on patient reported outcomes, health economics and other parameters.
Links:

ClinicalTrials.gov

Full title: Identifying Digital Endpoints to Assess FAtigue, Sleep and acTivities daily living in Neurodegenerative disorders and Immune-mediated inflammatory diseases
Summary: The study will be a multi-national, multi-centre longitudinal observational study with the aim to evaluate the performance of the candidate digital endpoints of fatigue and sleep disturbance in the following neurodegenerative disorders (Parkinson’s disease and Huntingdon’s disease) and immune-mediated inflammatory diseases (Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren’s syndrome). Healthy volunteers without symptoms of chronic fatigue or sleep disturbance will also be include as a comparative group.
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Full title: Immunome project consortium for AutoInflammatory Disorders
Summary: ImmunAID is seeking to enable a rapid and accurate diagnosis across all the spectrum of SAID, in order to improve clinical management of SAID patients, through a graded approach: - Identification and validation of novel Omics- and pathway-based diagnostic biomarkers, with a strong link to pathogenic pathways involved in autoinflammation, and likely to be considered as genuine “autoinflammation signatures”; - Development of a robust clinical decision algorithm to assist physicians, having a progressive and targeted approach (triage process) when facing a patient with suspected SAID, and thus avoiding the prescription of a large number of costly and frequently inadequate diagnostic investigations in parallel; The ImmunAID research will likely lead to the reorganization of SAID into a new comprehensive and pathogenesis-driven classification with strong clinical impact.
Links:

EU Community Research and Development Information Service (CORDIS)

Full title:
Summary: The objective of the LIVERHOPE project is to evaluate a novel therapeutic strategy for patients with cirrhosis based on a combination of rifaximin and simvastatin, targeting the main pathophysiological mechanisms of disease progression , namely the impairment in the gut-liver axis and the persistent hepatic and systemic inflammatory response. This dual therapeutic approach is supported by preclinical data showing excellent and very promising results. LIVERHOPE will include two randomized double-blind trials (LIVERHOPE SAFETY and LIVERSHOPE EFFICACY) to investigate safety, tolerability and efficacy of combination of simvastatin plus rifaximin in patients with decompensated cirrhosis in six EU countries (285 patients will be enrolled in two trials in Germany, France, Italy, Spain, The Netherlands, and the United Kingdom). The expected impact is to halt progression to acute-on-chronic liver failure, the main cause of death, to decrease complications of the disease, to reduce hospital re-admissions, to improve cost-effectiveness of therapy. The aim of the LIVERHOPE SAFETY trial is to assess the safety and tolerability of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis. The aim of LIVERHOPE EFFICACY is to assess the efficacy of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis to prevent ACLF development.
Links:

EU Community Research and Development Information Service (CORDIS)

 

Full title: Dry age-related macular degeneration: Development of novel clinical endpoints for clinical trials with a regulatory and patient access intention
Summary: The major objective is to develop novel clinical endpoints for clinical trials with a regulatory and patient access intention in patients with intermediate age-related macular degeneration (iAMD). Additional objectives are to characterise visual impairment in iAMD and its progression, as well as identify risk factors for progression to late stage AMD.
Links:

EU Community Research and Development Information Service (CORDIS), ClinicalTrials.gov

Full title: NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients
Summary: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease (AID) involving 0.5 to 3/1000 persons. The disease affects exocrine glands leading to dryness of the eyes and the mouth and is associated with fatigue and limb pain. In 30% to 50% of the patients, systemic and extra-glandular manifestations may develop. The spectrum of extra-glandular manifestations in pSS is broad and includes vasculitis, peripheral neuropathy, synovitis, kidney involvement and interstitial lung disease. Moreover, pSS patients have a 10 to 20-fold higher risk of developing B cell lymphomas, conferring shorter lifetime expectancy to these patients. Whereas 10 new targeted-immunomodulatory treatments have been marketed for rheumatoid arthritis in the past 20 years, only one drug has been licensed for other systemic AIDs, such as pSS and systemic erythematous lupus in the same period. There are several factors that may hamper the development of successful drugs for AID. Being multi-organ, these AIDs are considerably heterogeneous among individuals both in terms of clinical manifestations and biological disturbances, with, as a consequence, great difficulty to set-up accurate composite clinical end-points sensitive to change and usable in clinical trials. In this project, our objectives are: - To develop and assess sensitive clinical endpoints, for use in future clinical trials, able to evaluate response to drug treatments in patients with pSS with high disease burden and/or systemic involvement, - To identify and evaluate discriminative biomarkers for stratification of pSS patients predictive of organ involvement and disease progression and thus available for inclusion in clinical trials, - To set-up and perform an original multi-arm multi-stage clinical trial to validate the newly defined pSS endpoints and the identified biomarkers, by maximizing the chance of finding a difference between the placebo arm and the treated arm.
Links:

EU Community Research and Development Information Service (CORDIS)

Full title: A randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich’s Ataxia
Summary: Friedreich ataxia is a rare incurable and devastating disease. The clinical phenotype includes poor balance, impaired coordination, difficult articulation of speech and swallowing, distal weakness, deep sensory loss, visual and hearing impairment, but also heart failure, diabetes mellitus, scoliosis and foot deformities. Clinical manifestation normally starts around puberty. There is no cure or treatment that can slow down the disease which frequently results in severe disability by early adulthood. Friedreich ataxia is an inherited disorder caused by Frataxin deficiency. Nicotinamide (vitamin B3) was identified to increase Frataxin expression by an epigenetic mechanism in patients with Friedreich ataxia. This multinational study NICOFA will investigate randomized, placebo-controlled and double-blinded, whether high doses of nicotinamide are an effective treatment for Friedreich ataxia over a study period of two years. Study design and duration and number of patients to be included are based on our natural history data obtained in EFACTS (European Friedreich’s Ataxia Consortium for Translational Studies).
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Full title: Antibodies against Nogo-A to enhance plasticity, regeneration and functional recovery after acute spinal cord injury, a multicenter international randomized double-blinded placebo-controlled Phase II clinical proof
Summary: Spinal cord injury is a severe and devastating neurological disorder that leaves patients with permanent paralysis of the body. No treatment is available today to regenerate interrupted nerve fibers and repair the damaged spinal cord. The incidence of spinal cord injury is about newly injured 10’000 people per year in the EU, and due to an almost normal life expectancy more than 200’000 patients are living with a spinal cord injury in the EU. The impact on the individual quality of life is high, and social costs are enormous. Recent preclinical research in animal models succeeded to greatly enhance axonal sprouting, fiber regeneration and neuroplasticity following injuries of brain and spinal cord. These results warrant translation now to patients suffering from acute spinal cord injury. A previous phase I clinical study using intrathecal application of a nerve fiber growth promoting antibody against the growth inhibitory protein Nogo-A has shown in patients with complete spinal cord injury that this treatment is safe and well tolerated. The present study will enroll patients with various degrees of complete to incomplete acute spinal cord injury for a double-blind, placebo-controlled trial to test the efficacy of this antibody therapy to improve motor outcome and quality of life of tetraplegic patients. The enrollment of patients with different degrees of spinal cord injury is considered essential to reveal drug activity and eventual proof of concept in a broad patient population. Advancements in clinical trial design, improved prediction algorithms of clinical outcomes and development of surrogate markers (in cerebro-spinal fluid/serum and by neuroimaging) will allow for scrutinizing the effectiveness of this novel treatment in an unprecedented way. A positive outcome of this trial will represent a breakthrough for the future therapy of spinal cord injuries and beyond (traumatic brain injury, stroke, multiple sclerosis).
Links:

EU Community Research and Development Information Service (CORDIS)

Full title: A multi-centre, open-label, randomized, comparative clinical trial of two different doses of bone marrow autologous human mesenchymal stem cells plus biomaterial versus iliac crest autologous graft, for bone healing in non-union after long bone fractures
Summary: This clinical trial involves two comparative analyses: Comparison of efficacy in terms of superiority of hBM-MSCs + biomaterial (both experimental arms, low and high doses) versus iliac crest autologus graft (active comparator arm). The principal endpoint is bone consolidation at one year, defined as a combination of clinical and radiological improvements: radiological consolidation (considered as a new bone formation across the fracture site visible in 3/4 cortices, on at least 3/4 views, qualitative analysis) without pain (with and without weight bearing) and without further reoperation in the callus site. Comparison of efficacy in terms of non-inferiority (target delta of 0.10 points) of low dose hBM-MSC+Biomaterial versus high dose of hBM-MSC+Biomaterial. The principal endpoint is the radiological consolidation, measured in a scale from 0 to 1, considering the mean consolidation of 0.6875 points (quantitative analysis).
Links:

EU Clinical Trials Register, ClinicalTrials.gov

Full title: Oxytocin Treatment in neonates and infants (BaBies) with Prader-Willi syndrome: effects of intranasal administrations of oxytocin in infants aged from 0 to 3 months vs. placebo on sucking and swallowing (phase III clinical trial)
Summary: Prader-Willi syndrome (PWS) is a rare chronically debilitating and life-threatening disease without efficient treatment. It is a genetic neurodevelopmental disorder with neonatal poor feeding, requiring nasogastric tube feeding, and social skills followed by early onset of obesity, severe behavioural disturbances and comorbidities. Pre-clinical data supported the hypothesis that OXT rescues early phenotype and modifies the course of the disease via its potential neuromodulation effect, if administered in a post-natal short window of opportunity. This is a European phase III randomised double-blind placebo trial, already approved by EMA, evaluating the effects of early intranasal OXT in PWS neonates/infants. This trial is coordinated by Pr M Tauber (France) and sponsored by the Centre Hospitalier Universitaire de Toulouse will be conducted in 5 European countries (France, Belgium, Italy, Netherlands, and Germany).
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Full title: Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging with ‘Minimally-Invasive Segmental Artery Coil-Embolization’: A Randomized Controlled Multicentre Trial
Summary: PAPA-ARTIS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patient's quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.
Links:

EU Community Research and Development Information Service (CORDIS), ClinicalTrials.gov

Full title: PERsonalised MedicIne Trials
Summary: Scientific excellence, and acceptance by health authorities of results derived from research on personalised medicine require standards ensuring validity and reproducibility. The objective of PERMIT is to establish, with all relevant stakeholders and invited experts, recommendations ensuring the robustness of personalised medicine trials, which also requires validation of the stratification methods. In a series of workshops participants, partners and selected experts will address the various aspects of methodology, design, data management, analysis and interpretation in personalised medicine research programmes, with the objective to reach consensus and publish recommendations. A mapping of the literature will inventory methodological practice in the various steps of personalised medicine programmes (WP2) and identify needs in terms of standardised methodology. WP3 will address the design of the stratification and validation cohorts, including the issue of the statistical power and the quality of data. WP4 will focus on the use of the stratification algorithms and the robustness the stratification methods. WP5 will address the translational step needed to select treatments to be tested in each of the clusters. WP6 will be dedicated to randomized clinical trials testing treatments in each cluster (including umbrella / basket designs), or comparing the personalised vs. non-personalised approach. Recommendations and publications in scientific journals, a final meeting and webinars will foster adoption and implementation (WP7). The PERMIT consortium is composed of participants: pan-European research infrastructures (ECRIN, EATRIS, ELIXIR-LU/UNILU), funders (DLR), HTAs (KCE, ISCIII), patients (EPF), regulatory (ISS), data protection (TMF) and scientific experts, whereas partners represent stakeholders interested in the quality of evidence generated by personalised medicine research (industry, medicine agencies, ethics committees, funders, journal editors, HTAs, BBMRI).
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Full title: Prevention of Complications to Improve Outcome in Elderly Patients with Acute Stroke
Summary: Elderly patients have a high risk of complications after stroke, such as infections or fever. This study aims to assess whether preventive treatment in the first four days of hospitalisation with ceftriaxone, paracetamol, and/or metoclopramide prevents the most common complications and reduce the risk of death or long-term disability compared to standard care alone.
Links:

EU Community Research and Development Information Service (CORDIS), Trial website

Full title: Optimizing response to Li treatment through personalized evaluation of individuals with bipolar I disorder: the R-LiNK initiative
Summary: The objective of this study is to identify the eligibility criteria for treatment with Li in BDI in terms of response, safety and tolerability.
Links:

EU Community Research and Development Information Service (CORDIS)

Full title: REgenerative therapy of intervertebral disc: a double blind phase 2b trial of intradiscal injection of mesenchymal stromal cells in degenerative disc disease of the lomber SPINE unresponsive to conventional therapy
Summary: The primary outcome of this trial is to evaluate the effectiveness of intradiscal injection of bone marrow mesenchymal stromal/stem cells (BM-MSCs) in reducing chronic lower back pain (LBP) using the visual analog scale (VAS) and functional status (Oswestry scale) after 12 months of treatment, defining responders in case of at least 20% improvement in VAS or Oswestry scale at month 12 compared to a baseline with absolute change of 20 mm on a 100 mm scale.
Links:

Trial website

Full title: Safety and Effectiveness of SOFIA™/SOFIA™ PLUS when used for direct aspiration as a first line treatment technique in patients suffering an Acute Ischemic Stroke in the anterior circulation
Summary: Sesame is a European, multi-center, single arm, prospective, observational registry. Sesame aims to demonstrate that use of SOFIA™/SOFIA™ PLUS catheter for direct aspiration as a first line treatment technique is fast, safe and effective in patients suffering an Acute Ischemic Stroke when assessed at 24 hours, discharge and 90 days after treatment. 250 patients will be enrolled. All patients will be followed for 90 days or until death.
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Full title: Prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen
Summary: To define an optimal dosage of intravenous acetaminophen to close DA in EPI and thereafter to evaluate the consequence of early prophylactic acetaminophen treatment on mortality/morbidity at 36 weeks (w) of postconceptional age (PCA).
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Istituto Superiore di Sanità

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