Community Research and Development Information Service - CORDIS


ENSAT-HT Report Summary

Project ID: 633983
Funded under: H2020-EU.3.1.2.

Periodic Reporting for period 1 - ENSAT-HT (Application of omics-based strategies for improved diagnosis and treatment of endocrine hypertension)

Reporting period: 2015-05-01 to 2016-10-31

Summary of the context and overall objectives of the project

Arterial hypertension affects up to 45% of the general population and is responsible for 7.1 million deaths per year worldwide. However, optimal blood pressure control is not being achieved in up to two thirds of patients. Endocrine forms (E) of high (H) blood pressure (BP, EHBP), such as primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) and Cushing’s syndrome (CS) represent the most frequent forms of secondary and curable hypertension and thus major targets for stratified approaches of hypertension.

This project will develop and evaluate an omics-based stratified health promotion program for patients with EHBP.
The program is structured into 7 work packages (WP) interacting in a seamless and coordinated fashion. We will define specific omics profiles for patients with PA, PPGL and CS by integrating high throughput genetics, genomics and metabolomics data (WP2, WP3) with phenome annotations through bioinformatics modelling (WP1). Established profiles will be validated as stratification biomarkers and applied to the screening of referred hypertensive patients for both stratifying primary forms of hypertension for effective and cost efficient therapy as well as improving identification of endocrine causes for curative treatment and prevention of cardiovascular and metabolic complications (WP4). The program will be assessed for its medical, social, economic and ethical impact (WP5). Dissemination and communication will ensure international visibility as well as the optimal exploitation of the results of ENSAT-HT (WP6). Strategic and administrative management will be performed in WP7.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first period of the project the following work has been done:
Creation, development and maintenance of ENSAT-HT clinical data capture model including the development and roll out of a fully functional online registry has been achieved. A Research Data Management Database (RDMP) has been deployed and populated with sample data. Procurement, installation and configuration of infrastructure and hardware for hosting omics data within Safe Heaven environment have been realised. A systematic review of machine learning algorithms for omics dataset and investigation of publically available multi-omics datasets has been undertaken. Different processing pipelines for omics data management have been supported.

A full inventory and selection of samples archived at study centres has been realised and all required legal documentation to permit sample transfer has been prepared and submitted. A study protocol for WP2 and WP3 has been produced and made available to the consortium members. All groups have commenced their technical validation and pilot studies and these are all on schedule. Targeted sequencing kits have been developed to identify genotypes of EHBP and will be commercially available. Standard operating procedures (SOP) have been produced and made available on the consortium website.

Biosamples have been collected from over 235 samples of patients and analyses of plasma and urine catecholamines and steroids have been initiated. Targeted metabolomics profiling has been setup, showing good discriminant properties for further analyses. Studies on untargeted metabolomics have been initiated using 1H-NMR spectroscopy and QTOF mass spectrometry. Pilot experiments have been successfully performed to determine optimal sampling conditions and preparations and to study the influence of different factors. SOP for optimal sampling, labeling and sample transfer have been formalised and made available.

The clinical protocol of the first clinical study has been written and SOP for the measurement of blood pressure, screening for EHPB and hormonal assessment have been homogenized among centres. Criteria for the e-CRF have been established in collaboration with WP1, WP2 and WP5. The list of items has been provided to WP1 for the setup of the ENSAT-HT registry. SOP have been written for blood and urine sampling during the protocol. Four centres have submitted the protocol to their legal authorities and ethical approval was obtained in two. 30 patients have been included and their data entered in the ENSAT-HT registry.

A review of omics assessment methods used by the main health technology assessment (HTA) bodies has been undertaken, including only multi-analyte assays with algorithmic analyses (MAAA), cancer and non-cancer, non-companion (stand-alone) tests that are actionable and have been evaluated by at least one HTA body until May 2016. Twenty-five reports and articles have been finally taken into account regarding 17 MAAAs. The two main models used were the EUnetHTA Core model or the ACCE framework, which could be adapted to the assessment of MAAAs. The main assessment criteria used by these studies where clinical validity and utility, economic, ethical, legal and social aspects.

The classic communication tools for the project such as a logo, the website and a leaflet have been deployed. A press release was published by the coordinator at the start of the project and send for dissemination/appropriation to all partners. The missions of the Innovation Management Board that will be activated later in the project were presented at the kick-off meeting as well as an introduction by P13 to general Intellectual Property Issues in Research projects.

Management tools and templates for the scientific and financial monitoring of the project have been set up. The monitoring of the advances in the project has been started with regular updates to be delivered by the WP leaders. Two meetings with all partne

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

ENSAT-HT will provide innovative solutions for the development of better diagnostic biomarkers to improve identification of EHBP, with further exploration for stratifying patients with PHT. Results obtained through ENSAT-HT will lead to the development of new bioinformatic tools, data management solutions, the implementation of new statistical methods to deal with multi-signal assays in clinical practice and new HTA methods for their evaluation.

This project will have a strong impact on knowledge, by improving the understanding of the molecular and pathophysiological mechanisms involved in the most common forms of endocrine hypertension, allowing the redefinition of a novel, prognostically and therapeutically relevant disease taxonomy. Patient benefit will be derived from earlier, more precise and cost-efficient diagnosis, and from widespread availability of diagnostic tests outside from specialized referral centres, which has the potential to reduce health care disparity over the territory. Better informed medical decisions will improve therapeutic outcome thanks to better targeted therapies and earlier disease intervention, improving cure rate and QoL and reducing comorbidities.
A decrease in health care costs is expected from the early detection and improved effective and cost efficient treatment of EHBP at a subclinical stage and from prevention of cardiovascular and metabolic complications.

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