Despite the fact that iodine deficiency (ID) can easily be prevented by iodine fortification of table salt, industrial salt and cattle food, Europe belongs to the worst regions in terms of access to iodized salt and is seriously ID, resulting in the perpetuation of the single most important, preventable cause of brain damage. European ID is due to significant heterogeneity in prevention and monitoring programs, leading to inappropriate interventions, increased disease burden, health inequities and increased health care costs. Up to 360 Million European citizens are exposed to ID disorders. An effective European monitoring program is a crucial step towards eradication of ID disorders with significant benefits for European citizens and the sustainability of health care systems. The effects of ID in total cause tremendous, preventable costs in health care systems of affected regions.

The overall aim of EUthyroid is to evaluate ID prevention and monitoring programs in 24 European countries, to initiate capacity building for harmonized European ID prevention and monitoring programs, and to disseminate project outcomes for supporting measures on national and EU level in order to eradicate ID disorders in Europe. The project will position itself as international hub of current national initiatives in the attempt to coordinate and support existing national activities. EUthyroid will generate the first harmonized data set of ID resulting in the first valid map of iodine status in Europe. With a dedicated dissemination program about the unfavorable health outcomes of ID, EUthyroid will pave the way for a harmonized EU-wide regulation of iodination, a common approach to iodine and outcome monitoring and establish recommendations for scientists on how to monitor IDD prevention programs. The project aims to make Europe a benchmark for ID disorder prevention worldwide.

Website of the Project

The prevalence of diabetes in people ≥ 65 years approaches 25% (40% of all patients with diabetes are > 65 years). This number will increase 4-fold in people > 70 years in 2050. Diabetes results in a high personal and social health burden, and a significant public health burden in terms of rising healthcare costs. Diabetes is associated with increased functional decline in older people and may explain up to 20% of their excess risk of disability. Our project focuses on the use of interventions to improve functional status and enhance quality of life. This is justified because there has been a lack of intervention studies in this population and improvements in function and well-being may be of more clinical benefit in older patients than attention to metabolic control alone.

The MID-FRAIL STUDY is a Phase IIb open randomized clinical trial to evaluate the effectiveness of a multi-modal intervention (optimizing medical management, resistance-based exercise program and educational/nutritional intervention) in 1,704 frail or pre-frail subjects ≥ 70 years with T2D to prevent functional decline and maintain or improve quality of life and its associated costs.

This approach is original (both the intervention and outcomes are unique for studies in diabetes), relevant (it concerns 25% of people with diabetes), pertinent and feasible.

The project is highly aligned with objectives pursued by two topics of this call: investigator-driven clinical trials in elderly populations (HEALTH 2011 2.2.2-1) and in diabetes complications (HEALTH.2011.2.4.3-1).

The study aims to demonstrate a reduction of 20% in that risk, which will mean an annual prevention of around 700,000 incident cases of some disability in old people, with a major impact on global quality of life and financial costs. This is especially true in older women. Three research-intensive SMEs will play a leading role in this project and it also has the support of Diabetes UK, a major patient and family advocacy organisation

Website of the Project

Website of the Project

Stroke is the second leading cause of death in the world population. When not fatal, stroke often results in disability, due to motor and cognitive impairments, and secondary health problems affecting not only patients but also their families.
Building on emerging preclinical and pilot clinical evidences, RESSTORE will focus on the clinical assessment of regenerative cell therapy to improve stroke recovery and patients quality of life. RESSTORE European multicentre randomised phase IIb will explore, for the first time, the efficacy (functional recovery) and safety of intravenous infusion of allogenic adipose tissue derived mesenchymal stem cells (ADMSCs) in 400 stroke patients.

Therapeutic effects of ADMSCs will be assessed and monitored in patients using clinical rating scales, multimodal MRI and novel blood biomarkers. Additionally, the societal value and cost-effectiveness of ADMSCs-based regenerative therapy will be evaluated through health economics and predictive in silico simulations. Complementary ancillary animal studies will support the clinical trial by defining i) if the treatment response can be further enhanced by intensive rehabilitation, ii) the contribution of co-morbidities and iii) the mechanism(s) underlying the therapeutic effect.

The European regenerative therapy capacities (France, Spain, Finland, United Kingdom and Czech Republic), developed in RESSTORE will cover the full value chain in the field (large scale GMP cell production, clinical testing, biomarkers discovery, understanding of the restoring mechanisms, modelling, biobanking, economic studies, exploitation and communication plan). RESSTORE will thus surely contribute, together with the workforce trained in the context of the programme, to improve its public and private (SME) competitiveness and increase the attractiveness of Europe as a reference location to develop and clinically assess new innovative therapeutic options for brain diseases.

Website of the Project

Website of the Project

Cystic fibrosis (CF), a life-shortening genetic disease is characterized by abnormalities in the pulmonary, digestive, and other secretory systems leading to increased airway and systemic inflammation, oxidative stress, nutrient malabsorption, tissue catabolism, and ultimately, respiratory failure and premature death. Adequate nutritional status in CF, including maintenance of skeletal muscle (fat-free) mass, is tightly correlated with lung function and survival in this population. However, relatively little research exists to guide evidence- based optimal dietary recommendations regarding specific nutrients and food patterns in CF. Recent advances in high-resolution metabolomics (HRM) provide a unique opportunity to broadly explore metabolism and underlying pathways relevant to nutrition, disease exacerbation, and treatment in CF. Preliminary HRM data from Dr. Alvarez’s K01-supported research (K01 DK102851) indicated an enhanced catabolic state in adults with CF, as evidenced by dysregulation of plasma amino acids and lipids and their metabolic intermediates. The data also suggested that high-dose vitamin D3–previously shown to improve clinical outcomes–may mitigate catabolism in these subjects during an acute pulmonary exacerbation. Furthermore, key clinical outcomes before vitamin D3 intervention, such as lung function, were correlated with metabolic pathways directly linked to dietary intake and nutritional status. 

The purpose of this R03 study is to use plasma HRM with advanced bioinformatics to: 

1) identify specific nutrient-related metabolic processes that differ as a function of clinical status and are linked to important clinical outcomes;  

2) confirm an anti-catabolic/pro-anabolic effect of high-dose vitamin D3 in a completed prospective, randomized controlled trial. The overall goal of this project is to obtain new insight into the CF catabolic state during acute illness and recovery that will inform the design of future nutritional interventions to prevent depletion of fat-free mass.

Specific aims are to use plasma HRM to: 

1) compare the catabolic state of adults with CF during clinical stability vs. during acute pulmonary exacerbation, using healthy adults and adults with non-CF bronchiectasis as controls; 

2) investigate whether high-dose vitamin D3 has long-term anti-catabolic/pro-anabolic effects in adults with CF initially hospitalized for an acute pulmonary exacerbation;

3) conduct metabolome-wide association studies in Aim 1 and 2 CF subjects to determine if nutrient-related pathways are linked to convalescence and clinical outcomes over time. 

This R03 grant, in combination with Dr. Alvarez’s K01 training, will accelerate her transition to independence and will provide strong preliminary data for subsequent R01 studies. These will focus on the pathophysiology of catabolism in CF and development of new nutritional strategies to improve the health and quality of life in adults with CF, consistent with the mission of the NIDDK.