Note: As of December 2025, Evaluation and selection phase has been delayed until Q1/Q2 2026 (Please refer to new dates in Section 3. 'Application Process', below).
As of 11 September 2025, this Announcement of Opportunity has been updated to (i) reflect the integration of optional the ESA’s HRE Exploration Biobank as part of the campaign setup, (ii) clarify the eligibility criteria by specifying that proposal teams must not include members of the associated study facility responsible for implementing the core ThromBoShift protocol, and (iii) specify that all components of the proposal submission must be provided in English.
The Q&A virtual meeting material and link to the recording has been added (18 Sep 2025).
1. INTRODUCTION
ESA's Exploration Science Programme: Advancing Knowledge, Inspiring Innovation
The European Space Agency's Exploration Science Programme, a cornerstone of its Explore2040 strategy, invites scientists, researchers, and innovators to join us in pushing the boundaries of human knowledge and technological capabilities. Our programme uniquely balances exploration-focused science, essential for enabling future human missions beyond Earth, with exploration-enabled science that leverages our capabilities for groundbreaking research across disciplines.
We support a wide spectrum of scientific investigations, from understanding the impact of spaceflight on astronaut health and developing countermeasures and health monitoring tools for long-duration spaceflight, to exploring fundamental physics in microgravity, prospecting for lunar resources, and searching for signs of past life on Mars. The ESA Exploration Science Programme offers a platform to turn your scientific vision into reality.
To enable this breadth of research, we provide access to a diverse and evolving suite of platforms. These include ground-based analogues of spaceflight conditions, as well as the International Space Station, upcoming commercial low Earth orbit stations, and a range of lunar and deep space exploration initiatives, each offering unique environments and challenges.
Guided by core European values of collaboration, scientific excellence, and responsible exploration, we seek proposals that not only advance our understanding of the universe but also contribute to solving global challenges here on Earth. Our programme emphasises open science, international cooperation, and the inspiration of future generations.
Through this Announcement of Opportunity (AO), we invite proposals for research activities to be implemented within the “AO-2025-ThromBoShift” study. We welcome research proposals that explore thrombotic risk and fluid redistribution in support of safe and effective human spaceflight.
Background on Scientific Directions & Areas of Focus
Proposals submitted under this Announcement of Opportunity (AO) are encouraged to align with ESA’s Terrae Novae exploration programme, Europe’s flagship initiative for human exploration of the Solar System. Guided by the long-term vision of the Explore2040 strategy, Terrae Novae seeks to ensure a sustained European presence in low Earth orbit (LEO), enable human exploration of the Moon, and prepare for future missions to Mars. This scientific agenda is strongly informed by the goals of human health, performance, and sustainability across increasingly distant and demanding environments
In this context, the ThromBoShift campaign contributes to these strategic goals by investigating a critical and emerging health concern in spaceflight: the risk of venous thrombosis in the cephalic circulation. Triggered by the first in-flight detection of an internal jugular deep-vein thrombosis (DVT) aboard the International Space Station (ISS) and subsequent evidence of altered venous flow in other astronauts, ThromBoShift seeks to deepen our understanding of the vascular and haemostatic changes associated with cephalad fluid shifts in microgravity. The study will use head-down tilt bed rest (HDT) as a ground-based analogue to simulate fluid redistribution and enable a detailed, mechanistic assessment of thrombosis-related risk factors, without the use of countermeasures that might confound physiological responses.
Proposals are particularly encouraged in the following areas, which are key to ESA’s exploration science strategy:
- Crew Health & Performance: investigating thrombosis-related risk under cephalad fluid shift conditions; identifying early and progressive markers of venous dysfunction, coagulation imbalance, and endothelial response; enhancing clinical surveillance, physiological monitoring, and individualized risk stratification to safeguard astronaut health and performance during long-duration missions.
- Habitation: developing and validating compact, autonomous, and wearable point-of-care diagnostic technologies for vascular health and coagulation monitoring; enabling integration of medical monitoring tools into operational workflows in confined, resource-limited space habitats; supporting the implementation of real-time health assessment and decision-making capabilities for future exploration missions.
These strategic directions are further supported by ESA’s Exploration Science programme, as reflected in the SciSpacE white papers, and the papers published in "The Future of Science of Space Exploration: a European view", which outline a broad range of life and physical science disciplines relevant to exploration. These resources highlight research areas that address fundamental scientific questions whilst also enabling exploration and contributing to terrestrial applications.
In addition, ESA's ExPeRT (Exploration Preparation, Research and Technology) area coordinates the development of studies and technologies for future missions to low Earth orbit, the Moon, and Mars. This preparatory work is essential for Europe's participation in upcoming international exploration opportunities.
Applicants are encouraged to align their proposals with one or more of the strategic objectives outlined above. Clearly identifying which scientific directions or programme priorities are addressed, and how the proposed research contributes to advancing ESA’s exploration goals, will help ensure the relevance and impact of the submission
2. DESCRIPTION OF THIS OPPORTUNITY
Rationale and general overview
The ThromBoShift study addresses a critical and emerging concern in long-duration spaceflight: the risk of venous thrombosis in the cephalic circulation. This follows the first in-flight detection of an internal jugular deep-vein thrombosis (DVT) in an astronaut on board the International Space Station (ISS), an event that was asymptomatic but medically significant (Auñón-Chancellor et al., 2020). Subsequent ultrasound assessments have revealed jugular vein flow stasis in other crew members, suggesting that subclinical thrombotic events may be more common than previously understood.
These findings point to a broader alteration in venous function under microgravity conditions, potentially driven by cephalad fluid shifts, endothelial dysfunction, and inflammatory responses. This concern is further underscored by the current absence of in-flight diagnostic capabilities for coagulation monitoring. Addressing this gap, particularly through the development of miniaturized, point-of-care technologies, remains a critical priority in operational space medicine.
ThromBoShift is designed as a descriptive, observational study aimed at generating a holistic understanding of the mechanisms behind altered blood flow and thrombotic risk in the cephalic circulation. The protocol will be conducted without the implementation of systematic countermeasures, thereby enabling an unbiased characterization of physiological changes in response to long-duration spaceflight. As the induction of thrombosis is neither expected nor ethically permissible, the study is not intended as a direct assessment of clinical risk but rather as a mechanistic investigation of vascular and hemostatic responses. To ensure participant safety and data integrity, dedicated clinical surveillance of thrombosis risk, independent of experimental measurements, will be implemented throughout the study duration.
NOTE: The implementation of this study is subject to formal funding confirmation by the ESA Ministerial Council, scheduled for November 2025. Upon Ministerial Council outcome and budget availability, preparatory activities will commence following proposal selection and approval.
Protocol Structure
The ThromBoShift protocol accommodates both standard HDT measures and surveillance assessments of thrombosis risk aligned with the study’s scope. In addition, it will incorporate the ESA scientific complement resulting from the selection of proposals under this Announcement of Opportunity (AO).
- Baseline Data Collection (BDC):
- Duration: 14 days with uninterrupted presence at the facility.
- Execution of standard measurements, surveillance assessments of thrombosis risk study measurements, and measurements from science teams/proposals.
- Head-Down Tilt Bed Rest (HDT):
- Duration of 60 days.
- Continuous 6° HDT without a pillow, and without any implementation of systematic countermeasures.
- Execution of standard and surveillance study measurements, and measurements from science teams/proposals.
- Optional (for science teams/proposals): limited, transient physiological stimulation tests may be considered if non-interfering.
- Recovery Phase (R):
- Duration: 14 days with uninterrupted presence at the facility.
- Execution of standard and surveillance study measurements, and measurements from science teams/proposals.
- Follow-Up (R):
- The study foresees the inclusion of standalone follow-up measurements at R+28.
Note: Added measurements from science teams/proposals cannot include any countermeasures. Only observational measurements will be accepted.
Experimental Design
- Number of participants: 20 participants will undergo 60 days of continuous head-down tilt bed rest (HDT). All subjects will follow the same protocol; no separate cohorts or group divisions are foreseen. The study design is structured to achieve its statistical objectives within a single, unified sample.
- Design: A single-cohort, observational study under a uniform protocol.
- Sex Balance: Equal representation of male and female participants is prioritized (aiming for 50/50 split).
- Age Range: Subjects between the ages of 25 and 45 will be included.
- Countermeasures: None systematically applied; observational focus only.
- Clinical and Paraclinical Monitoring: Dedicated (para)clinical monitoring for asymptomatic thrombosis and vascular health.
The protocol is structured to support integrative analysis of thrombotic mechanisms, with flexibility to accommodate complementary research activities that align with the study’s operational constraints and scope.
To ensure scientific coherence and operational feasibility, submitted proposals should be designed to align with the overall ThromBoShift protocol structure. This includes fitting within the defined study phases (BDC/HDT/R (Recovery and Follow-up), adhering to the proposed timelines. Investigators are encouraged to tailor their protocols to leverage the unique characteristics of each study phase, while remaining compatible with the sample size considerations. In doing so, they should refer to the standard measurement overview and timing outlined in Annex 1, and are advised to indicate both their preferred and acceptable time windows for each measurement to facilitate scheduling flexibility. Proposals that demonstrate adaptability to this shared structure will be prioritized for integration into the ThromBoShift campaign.
Furthermore, the implementation of the core ThromBoShift protocol, including all study phases and standard measurements, will take place at a dedicated study facility designated by ESA. This facility will provide the operational framework and infrastructure for the campaign, within which selected science teams will integrate their investigations.
Science Objectives
In addition to aligning with the ESA research strategy and programmatic focus areas, this Announcement of Opportunity invites proposals that leverage the ThromBoShift study as a targeted analogue for investigating thrombotic risk in spaceflight, with particular emphasis on the detection of asymptomatic thrombosis as a principal endpoint.
The following scientific objectives are intended to guide proposal development.
a. Hemodynamic and Fluid Shift Dynamics
- Investigate how prolonged strict HDT affects venous return, flow velocity, and pressure in the internal jugular vein and other upper body vessels.
- Determine the contribution of cephalad fluid shifts to flow stasis or retrograde flow in the jugular vein and how these dynamics evolve over time.
b. Thrombotic/Antithrombotic Balance
- Assess how classical coagulation markers (e.g., fibrinogen, thrombin-antithrombin complexes, von Willebrand factor, D-dimer) are modulated during HDT.
- Evaluate temporal changes in platelet function and fibrinolysis in this analogue environment.
c. Endothelial and Inflammatory Responses
- Examine the effects of HDT on endothelial function and inflammatory markers associated with vascular health and thrombotic risk.
- Identify early biological signatures that may predict individual susceptibility to thrombotic events.
d. Neuro-ocular and Cerebrovascular Links (SANS-related)
- Characterize concurrent changes in blood flow and vascular regulation in regions implicated in SANS.
- Explore potential mechanistic links between altered venous drainage and ocular changes.
e. Sex-Based Differences
- Evaluate sex-specific physiological responses in coagulation, endothelial function, and fluid shifts during prolonged bed rest.
- Compare timelines and magnitudes of change in thrombotic risk markers between male and female participants.
f. Detection, Monitoring, and Technology Demonstrations
- Identify and evaluate miniaturized, wearable, or point-of-care technologies for real-time monitoring of coagulation, vascular health, and vital signs in analogue or spaceflight conditions.
- Assess the utility of non-invasive imaging (e.g., Doppler ultrasound, Vector Flow Imaging) and biosensors for detecting subclinical thrombosis and physiological changes.
- Demonstrate integrated systems combining diagnostics, biosensors, and imaging technologies under space-relevant operational constraints.
- Evaluate the performance, usability, and readiness of autonomous health assessment tools, including medical AI and closed-loop systems for decision support and adaptive countermeasure guidance.
g. Translational and Modelling Approaches
- Evaluate the potential of biomedical models (derived from stem cells or induced pluripotent stem cells (iPSCs)) to replicate physiological effects observed in subjects.
- Investigate whether biomedical models can be used to delineate the mechanism of thrombosis development in subjects.
- Assess the predictive capacity of biomedical models in identifying individuals at elevated risk of thrombosis.
- Note for biomedical models: The use of microgravity simulation platforms (e.g. Clinostats and Random Positioning Machines) can be supported by the Agency.
Note: Depending on the scientific complement and the level of interest in exploration-focused science, non-exploration focused/enabled research not tackling the above priorities but addressing groundbreaking community questions may also be accommodated—though subject to available capacity.
Standard Study Measurements and Data Access
A core set of standardized and surveillance measurements will be collected across all participants in the ThromBoShift campaign. A preliminary overview of these measurements is provided in Annex 1, split in two sections: ESA BR Standard Measures and ESA Medical Surveillance Measures.
Please note: the final list of standard measurements will be confirmed during the study preparation phase and may be subject to change based on feasibility assessments, potential conflicts between measurements, and resource constraints. To support collaborative research and maximize scientific return, ESA will establish data-sharing agreements that allow science teams access to these datasets.
Applicants must clearly indicate in their proposals which specific standard datasets they intend to use and how these will support their research objectives. This will help ensure appropriate data provisioning and alignment with the study’s operational planning.
3. APPLICATION PROCESS
All components of the proposal submission must be provided in English, including the content of the online submission form and any uploaded attachments or supporting documents.
Kindly submit your completed proposal template (Annex 2) by clinking on the “Submit Your Idea” button below. Complete all sections of the submission form as per guidelines outlined in the call, respective attachments and in the provided proposal template, and upload any additional information as required. ESA will organise a Q&A virtual meeting to present the details of the call and the associated facility, and to address any questions from prospective proposers. This session is intended to support interested teams in preparing strong and well-informed proposals.
Whilst preparing their proposals, applicants are required to contact their respective national space agencies to inform them of their intended submission. This step is essential to explore potential national funding procedures, timelines, and likelihood of support, and to identify alternative funding sources if necessary. (refer to "Who can apply?" section, below).
Note: Any additional measurements proposed by the science teams (e.g., MRI, muscle biopsies) that fall outside the standard protocol (i.e., bedrest standard measures, or ESA Medical Surveillance Measures) will not be covered by ESA and thus must be fully funded by the proposing teams themselves. Furthermore, the inclusion of such measures is not guaranteed and will depend on both operational feasibility and resource availability within the study framework.
If you have any further technical questions during submission, feel free to contact the Campaign Manager.
Please ensure that all team members complete and sign the Privacy Consent Form (Annex 3) and include them as part of the proposal submission.
The schedule for this Announcement of Opportunity is as follows (please note dates are tentative):
Launch of Announcement of Opportunity: 09/07/2025
Notification of Selection due: Not before Mid 05/2026
Preparation of the study: 01/06/2026 - 30/11/2026 (Tentative)
Investigator Working Group meeting #1 Q3 2026
Investigator Working Group meeting #2 Q1 2027 (Tentative)
Science teams interested to apply are invited to submit a Letter of Intent (LoI), using the template that you can find in the attachments. You can submit the LoI via the submission form and you can then later supplement/update your idea with the full proposal requirements. This LoI allows us to give feedback to your project if needed. Please note that a LoI is non-binding and not mandatory. Even if you submit a LoI, you can deviate from it for your full proposal and even if you do not submit a LoI, you are still eligible to submit a full proposal.
Please note that you can use also the OSIP platform to ask any questions in case of uncertainties.
4. IMPLEMENTATION OF THE SELECTED PROPOSALS
Following a positive peer and technical review, the scientific coordinator of each selected proposal will be notified that the project has advanced to the definition phase and will be added to a pool of candidate activities. It is the responsibility of the scientific coordinator to inform the rest of the science team of this preliminary selection. Upon selection, the science team will be required to provide experiment-specific documentation and will be required to support coordination meetings to define the scientific requirements and prepare for experiment implementation. Please note that selection for definition phase does not guarantee implementation. Feasibility issues may arise during the definition process.
Once the notification of selected proposals has been communicated, each selected science team will be required to prepare an Activity Requirements Document (ARD), outlining all aspects of the proposed experiment. Following the completion of the experiment, a Data Blank Book (DBB) must be completed to document all acquired datasets for archiving purposes. Additionally, ethical approval and medical board clearance must be obtained before any experiment can proceed to implementation.
This Announcement of Opportunity only provides access to the Head-Down Tilt Bed Rest study and its volunteer cohort. Science teams are responsible for securing funding to cover all associated costs, including personnel time, travel expenses, required equipment, and any on-site, experiment-specific measurements (e.g., MRI, muscle biopsies, etc), shipment of physical samples from the study facility to the science team's premises or laboratories, as well as other operational needs to support their activities. Applicants are therefore expected to initiate their funding requests in parallel with the preparation of their proposal (see “Who can apply?” section below).
Given logistical and facility considerations, the study may be implemented across two separate campaigns, each comprising the same phases: BDC, Head-Down Tilt Bed Rest (HDT), Recovery and Follow-Up. Due to facility constraints, participants in each campaign will be organized into sub-groups based on the availability bed rest beds. As a result, data collection will be staggered, and scientific teams conducting complex or time-sensitive measurements should anticipate multiple travel periods to align with the different participant sub-groups. We strongly recommend that applicants reflect this in their funding requests, ensuring adequate resources are allocated for travel and associated logistics.
ESA reserves the right to select only specific components of a submitted proposal if those elements are deemed to have high scientific merit. In such cases, the applicant will be given the option to accept or decline the partial selection. If two or more proposals address similar scientific questions or methodologies, ESA may request that the respective science teams consolidate aspects of their projects into a single collaborative effort.
NOTE: The implementation of this study is subject to formal funding confirmation by the ESA Ministerial Council, scheduled for November 2025. Upon Ministerial Council outcome and budget availability, preparatory activities will commence following proposal selection and approval.
Contribution to ESA’s HRE Exploration Biobank
ESA is establishing an HRE Exploration Biobank to enable future research opportunities by preserving biological samples collected during exploration-related studies. As part of the campaign setup, science teams submitting proposals for the IBRIS campaign will be asked to formally acknowledge their awareness of the biobank initiative where participation involves making residual sample fractions from their approved investigations available for long-term storage in the ESA HRE Exploration Biobank. The detailed process, including documentation requirements, ethical considerations, and applicable standards, will be communicated at a later stage during the study preparation phase. Formal agreements, where applicable, will also be addressed at that time. Please note that any contribution of residual samples will require participant consent and inclusion in the relevant ethical approvals prior to implementation.
5. DATA RIGHTS AND DATA MANAGEMENT RESPONSIBILITIES
Please ensure you are familiar with the data rights, data ownership, and the data management responsibilities applicable to the datasets a selected science team will acquire as part of the campaign as described in the ESA HRE Data Policy (see Annex 5).
Publications and Acknowledgement
Any publication of the results generated in the context of this research announcement of opportunity shall be provided to ESA and must acknowledge the sponsorship of the study by the European Space Agency. Additionally, the title of the publication shall include the name of the corresponding campaign, i.e., ThromBoShift.
Example/Reference:
“This research was carried out within the framework of the ThromBoShift study and was supported by the European Space Agency (ESA). The authors acknowledge the sponsorship of the European Space Agency under the associated Announcement of Opportunity (AO-2025- ThromBoShift), with reference number [XXXXX].”
Support of Education and Outreach
The activities covered in this research announcement provide an opportunity for the European Space Agency to engage the public and offer opportunities for education and outreach. Science Teams are encouraged to promote and communicate their investigations to a wide audience (general public, colleagues, involvement of students, social media) and to support the European Space Agency in the event of organized press conferences, social media events, educational activities, publications, etc.
