Speckle Technology and Digital Biomarkers of Microvascular Function for Monitoring Cardiovascular Diseases

Project Information

STIMULUS

Grant agreement ID: 101115492

DOI

10.3030/101115492

EC signature date 21 June 2023

Start date 1 October 2023

End date 30 September 2027

Funded under

• The European Innovation Council (EIC)

Total cost

€ 4 613 881,50

EU contribution

€ 4 578 881,50

Coordinated by

TURUN YLIOPISTO
Finland

Periodic Reporting for period 2 - STIMULUS (Speckle Technology and Digital Biomarkers of Microvascular Function for Monitoring Cardiovascular Diseases)

Reporting period: 2024-10-01 to 2026-03-31

Summary of the context and overall objectives of the project

Over 60 million people in the EU live with cardiovascular diseases (CVDs), at an annual economic cost of +210B€. Despite being largely preventable, CVDs cause more than 18.5 million deaths every year. To combat this, we develop new instruments for assessing adverse changes in microcirculatory status linked to hypertension, chronic kidney disease (CKD), and heart failure (HF), leading to earlier detection of CVDs. The instruments are developed and validated in clinical trials. We integrate two state-of-the-art technologies leading to a novel innovation, 3D speckle tissue monitoring. In addition, we demonstrate a direct use-case for unobtrusive monitoring in a smart toilet application.

Global remote patient monitoring (RPM) systems market is expected to surpass 5 B$ by 2030 with a Compound Annual Growth Rate (CAGR) of 20%. The demand for the RPM systems is rapidly growing among the old age population. Monitoring innovations targeting this group can reduce hospitalization and costly chronic conditions. Furthermore, the technology is closely linked to wearable remote monitoring. The global wearable technology market is expected to grow to 392 B$ by 2030 with a CAGR of 13.9%. The opportunity is significant as the number of wearable users currently exceeds 1 billion globally, and the developed technology targets similar markets. We currently estimate that with the new instrument and digital biomarkers we can reduce the healthcare burden by over 30% by preventing CVDs. Additionally, we are aiming to identify citizens at risk of developing hypertension, CKD and/or HF and by timely intervention, we expect to reduce indirect healthcare costs by over 20%. In conclusion, our solution will integrate two existing state-of-the-art methods and provide clearly new monitoring techniques to assess the microcirculatory status, revealing early signs of CVDs. We aim to provide an innovative solution to emerging digital unobtrusive health markets while helping the over 60 million Europeans suffering from CVDs.

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

For both heart failure and chronic kidney disease patients, it is important to diagnose microvascular dysfunction and monitor the deterioration of microvascular function in early phases of the disease progress. Our proposed technology, the HEMI-speckle system, is an integrated solution of two existing prototypes, namely, the multi-spectral optical sensory system (HEMI) and the speckle plethysmography (SPG) system. To understand the diagnostic value of these technologies for both HF and CKD populations, two clinical trials will be executed. At the same time, the new integrated solution will be developed. Prior to conducting the validation trial, adjustments can be made to existing individual technologies to ensure the trial is conducted properly in a patient population in a clinical setting. Lessons learnt from these clinical trials can be used a) for the development of the integrated HEMI-speckle system, b) to identify new digital biomarkers from the individual and integrated technology, c) to analyse the sensitivity and specificity of the two technologies for each population separately, and d) to prove the validity of the technologies for the early assessment of microvascular function in the target population. A third clinical trial will run in a later phase, when the HEMI-speckle prototype is ready. In this trial, the new technology will be verified on healthy volunteers and hypertensives, after the validation of the underlying technologies on a relevant patient population has been done. The additional new digital biomarkers obtained from the unique combination of the two individual technologies can be explored in this phase.

During the second reporting period, STIMULUS achieved its second and third milestones: M2, Ethics committee approval for clinical trials II, and M3, Recruitment closed for clinical trials I. By the end of the period, the TRL level of the HEMI and SPG devices have been improved after clinical trials I, to better suitability for clinical environments. This led to the final prototype devices for the clinical trials IIa and IIb. Additionally, the first functional prototype of the HEMI-speckle device has been created, and a first prototype of the smart toilet demonstrator has been developed and tested. The SPG and HEMI prototypes have been demonstrated at the European Society of Hypertension conference to clinicians and researchers. Datasets of measurements from healthy volunteers with the HEMI device and SPG device have been acquired and data processing algorithms have been developed. The first possible biomarkers for microcirculation function have been examined. The first results of these analyses have been presented at scientific conferences.

Additionally, the development of SMI-VCSEL miniature monolithic blood flow dynamics sensor started after a Hop-on partner joining the consortium in the second reporting period. During the reporting period, the design, assembly, and initial testing of the miniature monolithic SMI-VCSEL blood-flow dynamics sensor were carried out.

Health technology assessment (HTA) is an integral part of the project activities. One of the key roles of HTA is to provide prospective knowledge about the possible or probable consequences of new and emerging technologies. In the process, intended and non-intended impacts of the technology application are identified. Anticipating the spectrum of possible consequences of technology, at an early stage, helps to make good use of the potential of progress and to be able to minimize risks or even to avoid them. By the end of the second reporting period, the Ethical, Legal and Social Aspects (ELSA) have been addressed, firstly by conducting a literature review and complemented by a thorough analysis of the discussions amongst the relevant partners. The analysis is ongoing, and its findings will be documented in the forthcoming Deliverable 5.1 Report on Ethical, Legal and Social Assessment, to be delivered at the beginning of the next reporting period. Stakeholder engagement workshops involving healthcare professionals are being planned. STIMULUS uses a stakeholder-driven methodology to promote active participation and dialogue, enabling the co-creation of research outcomes. This approach ensures that the research conducted within the project reflects the values, needs and expectations of society.

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)

The global remote patient monitoring systems market was estimated at USD 965 million in 2021 and is expected to surpass USD 5 billion by 2030, poised to grow at a Compound Annual Growth Rate (CAGR) of 20% during the forecast period 2022 to 2030. The increasing adoption of digital technologies in the global healthcare industry is significantly driving the remote patient monitoring (RPM) systems market. The demand for the RPM systems is rapidly growing among the old age population, as this age group needs continuous monitoring of their health conditions. The number of people aged 60 years or above is expected to reach 2.1 billion by 2050. Monitoring innovations targeting this group can reduce hospitalization and costly chronic conditions, and hence help reduce the healthcare costs for the citizens. Furthermore, the technology is closely linked to wearable remote monitoring, mostly including photolethysmographic devices. The global wearable technology market is expected to grow to 392 B$ by 2030 with a CAGR of 13.9%. The opportunity is significant as the number of existing users for wearables currently exceeds 1 billion globally, and the developed technology targets similar use-cases and form factors. As the global prevalence of cardiovascular diseases is rising, our unique innovation to detect cardiovascular diseases early will have great market potential. To protect future commercial interests, two patents for the technology this project is based on, have already been obtained and others are pending. Also, the novel technology developed in this project will be similarly protected.