Artificial intelligence to predict cardiovascular risk recurrence in people with type 2 diabetes

ISRCTN	ISRCTN15690435
DOI	https://doi.org/10.1186/ISRCTN15690435
Sponsor	Navarre Health Research Institute Foundation (IDISNA)
Funder	Department of Health of the Government of Navarre

Submission date: 01/04/2026
Registration date: 23/04/2026
Last edited: 28/08/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
People with type 2 diabetes have a higher chance of having further heart or blood vessel problems after an initial event. Current tools used by doctors to estimate this risk are limited because they do not include information from many different sources. This study aims to develop a new way to predict future cardiovascular events by combining clinical information, blood tests, genetic data, gut microbiome samples and data from wearable devices. The goal is to create a more accurate prediction tool that could help guide care in the future.

Who can participate?
Adults aged 40 to 70 years with type 2 diabetes who have had a major cardiovascular event in the past 12 months can take part. They must be able to give written consent and use wearable monitoring devices. People with advanced heart failure, chronic dialysis, active cancer, severe infections or blood disorders, uncontrolled psychiatric conditions, significant cognitive problems, or those in other studies that could affect results cannot take part.

What does the study involve?
This is an observational study, meaning participants do not receive any treatment as part of the research. The study involves collecting information from clinical records, blood samples, genetic tests, gut microbiome samples and wearable devices that measure daily activity, heart rate and sleep. Participants will be followed for 24 months to check whether they have new cardiovascular events during this period.

What are the possible benefits and risks of participating?
There is no direct medical benefit for participants. However, the information gathered may help improve future prediction tools for people with type 2 diabetes. The risks are minimal and relate mainly to routine procedures such as blood tests and the inconvenience of wearing a monitoring device. There is no change to usual medical care.

Where is the study run from?
The study is being carried out in Navarra, Spain, through hospital and primary care centres.

When is the study starting and how long is it expected to run for?
April 2026 to December 2029.

Who is funding the study?
Department of Health of the Government of Navarre (Spain)

Who is the main contact?
Mr Alcibiades Segundo Diaz Vera, as.diaz.vera@navarra.es

Contact information

Mr Alcibiades Segundo Diaz Vera
Scientific

AV. PIO XII, 6, 6 A.
Pamplona
31007
Spain

ORCID ID	0000-0002-3715-1713
Phone	+34 617321081
Email	as.diaz.vera@navarra.es

Mr Gonzalo Luis Alonso Salinas
Principal investigator

AV. Sancho el Fuerte 24, 3C
Pamplona/Iruña
31007
Spain

ORCID ID	0000-0001-5914-8526
Phone	+34 617106968
Email	Gonzalo.AlonsoSalinas@unavarra.es

Mr CedrIc Marco Dechart
Public

Calle Iturrama 37
Pamplona/Iruña
31007
Spain

ORCID ID	0000-0002-4310-9060
Phone	+34 627666017
Email	cedric.marco@unavarra.es

Study information

Primary study design	Observational
Observational study design	Cohort study
Scientific title	CARDIO-DIABETES AI: Multimodal machine learning-based risk stratification of cardiovascular recurrence in patients with type 2 diabetes
Study acronym	CARDIO-DIABETES AI
Study objectives	This is a prospective observational cohort study in patients with type 2 diabetes and a recent cardiovascular event. The aim is to develop and internally validate a multimodal machine learning model to predict recurrent cardiovascular events in a secondary prevention setting. The primary outcome is recurrent cardiovascular events over 24 months. The study is justified by the limitations of current risk prediction models, which do not integrate multimodal biological and physiological data.
Ethics approval(s)	Approved 27/08/2025, Research Ethics Committee with Medicines of Navarra (CEIm-NA) (Hospital Universitario de Navarra, Irunlarrea 3, Pamplona/Iruña, 31008, Spain; +34 848 422497; ceim@navarra.es), ref: PI_2025/103
Health condition(s) or problem(s) studied	Type 2 diabetes mellitus and cardiovascular disease (secondary prevention of cardiovascular events)
Methodology	Current methodology as of 25/08/2026: This is an observational study with no intervention and data collection only, including clinical, biological and wearable-derived variables. A total of 250 patients aged 40–70 years will be recruited from hospital and primary care settings in Navarra, Spain. Clinical, genomic and polygenic risk score data, gut microbiome and metabolomic data, inflammatory and oxidative-stress biomarkers, NMR-based lipid and lipoprotein data, and longitudinal wearable-derived data will be collected and integrated for multimodal prediction modelling. Previous methodology: Observational study with no intervention. Data collection only, including clinical, biological and wearable-derived variables. A total of 250 patients aged 40–70 years will be recruited from hospital and primary care settings in Navarra, Spain. Clinical, biological and wearable data will be collected.
Intervention type	Other
Primary outcome measure(s)	Recurrent major cardiovascular event, defined as a composite of acute coronary syndrome, atherothrombotic stroke, arterial revascularisation, and cardiovascular death, measured using clinical assessment and electronic health record verification at the 24-month follow-up period Previous primary outcome as of 25/08/2026: Recurrent major adverse cardiovascular events (MACE), measured using clinical assessment and electronic health record verification as a composite outcome (acute coronary syndrome, atherothrombotic stroke, vascular revascularisation or cardiovascular death) at 24 months
Key secondary outcome measure(s)	All-cause mortality measured using individual components of major adverse cardiovascular events at 24 months Individual components of major adverse cardiovascular events measured using clinical assessment and electronic health record verification at 24 months Incidence of acute coronary syndrome, atherothrombotic stroke, arterial revascularisation, and cardiovascular death, measured using scheduled clinical assessments and electronic health record verification at 6 monthly time points throughout the 24-month follow-up period All-cause mortality, measured using scheduled clinical assessments and electronic health record verification at 6 monthly time points throughout the 24-month follow-up period
Completion date	31/12/2029

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	40 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	250
Key inclusion criteria	1. Adults aged 40–70 years 2. Confirmed type 2 diabetes mellitus 3. History of a major cardiovascular event within the previous 12 months (including acute coronary syndrome, atherothrombotic stroke or arterial revascularisation) 4. Able to provide written informed consent and willing and able to use wearable monitoring devices
Key exclusion criteria	Current key exclusion criteria as of 25/08/2026: 1. Advanced heart failure requiring palliative care, ventricular assist support or evaluation for heart transplantation 2. Chronic dialysis 3. Long-term home oxygen therapy 4. Active malignancy or life expectancy of less than 3 years 5. Severe haematological disorders 6. Severe active infectious disease 7. Uncontrolled major psychiatric illness 8. Significant cognitive impairment 9. Inability to ensure adequate follow-up 10. Inability or unwillingness to use the study wearable device 11. Participation in another study that could interfere with study outcomes or adherence Previous key exclusion criteria: 1. Advanced heart failure requiring palliative care or transplant evaluation 2. Chronic dialysis 3. Active malignancy or life expectancy less than 3 years 4. Severe haematological or infectious diseases 5. Uncontrolled psychiatric disorders 6. Significant cognitive impairment 7. Inability to ensure follow-up or comply with wearable device use 8. Participation in other studies that may interfere with the study outcomes
Date of first enrolment	01/09/2026
Date of final enrolment	31/08/2027

Locations

Countries of recruitment

Spain

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan	The datasets generated during and/or analysed during the study may be made available upon reasonable request from Alcibíades Segundo Díaz Vera (alcibiadessegundo.diaz@unavarra.es), subject to applicable ethical, legal, data-protection and institutional requirements. Data potentially available for sharing may include anonymised participant-level data underlying published study results, associated data dictionaries, and analytical code, where such sharing is legally and ethically permissible. Data would become available following publication of the main study results and would remain available in accordance with applicable institutional data-retention policies. Access would be considered for bona fide researchers submitting a scientifically justified proposal for research purposes compatible with the original study objectives and participant consent. Requests would be subject to review and approval by the study investigators and relevant institutional bodies, and a data-use agreement may be required. Directly identifying information will not be shared. Genomic and other potentially re-identifiable data will only be shared where permitted by participant consent, applicable data-protection legislation, ethical approval and institutional policies.

Individual participant data (IPD) Intention to share

Yes

IPD sharing plan

The datasets generated during and/or analysed during the study may be made available upon reasonable request from Alcibíades Segundo Díaz Vera (alcibiadessegundo.diaz@unavarra.es), subject to applicable ethical, legal, data-protection and institutional requirements. Data potentially available for sharing may include anonymised participant-level data underlying published study results, associated data dictionaries, and analytical code, where such sharing is legally and ethically permissible. Data would become available following publication of the main study results and would remain available in accordance with applicable institutional data-retention policies. Access would be considered for bona fide researchers submitting a scientifically justified proposal for research purposes compatible with the original study objectives and participant consent. Requests would be subject to review and approval by the study investigators and relevant institutional bodies, and a data-use agreement may be required. Directly identifying information will not be shared. Genomic and other potentially re-identifiable data will only be shared where permitted by participant consent, applicable data-protection legislation, ethical approval and institutional policies.

Editorial Notes

28/08/2026: The following changes were made:
1. The date of first enrolment was changed from 01/04/2026 to 01/09/2026.
2. The date of final enrolment was changed from 31/03/2027 to 31/08/2027.
3. The key secondary outcomes were added.
4. The ethics approval date was changed from 09/12/2025, when the formal certificate was provided, to 27/08/2025, when the favourable opinion was issued.
5. The individual participant data sharing plan was added.
25/08/2026: The following changes were made:
1. The primary outcome was updated.
2. The key exclusion criteria were updated.
3. The methodology was updated.
02/04/2026: Trial's existence confirmed by the Research Ethics Committee with Medicines of Navarra (CEIm-NA).