Subclinical Atherosclerotic Cardiovascular DiseaseMISTICNCT07520643
MISTIC Study: Atherosclerosis, Neurocognition & Cardiovascular Signaling
An observational study of Subclinical Atherosclerotic Cardiovascular Disease and Neurocognitive Decline, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The MISTIC study is a non-profit, cross-sectional clinical research project aimed at investigating the relationship between atherosclerosis and both cardiovascular and cognitive function in adult populations. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Subclinical Atherosclerotic Cardiovascular Disease, Neurocognitive Decline
- What is being tested?
- Peripheral Vascular Imaging, Coro-CT and Neurocognitive Assesment
- Type of treatment
- Surgery or procedure
- How many people
- 1,000 participants
- Where
- 1 siteItaly
- Study dates
- 1 May 2026to 30 Apr 2030
- How long will I take part?
- 6 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study includes 1000 participants recruited at Fondazione Policlinico Gemelli: 500 patients with advanced atherosclerosis undergoing PCI with ≥50% stenosis or documented coronary artery disease, and 500 control subjects from the Primary Cardiovascular Prevention Clinic with indications for CAC scoring, without prior acute coronary events. About 22% of controls may have subclinical atherosclerosis. Cognitive impairment is expected in 12-20% of patients and 4-10% of controls. All participants will undergo a single-timepoint assessment including clinical, imaging, molecular, and neurocognitive evaluations to study the association between vascular burden and cognitive function.
Who may be able to join
- Age >= 18 years
- Capacity to provide informed consent
- Documented coronary artery stenosis ≥ 50 % through peripheral vascular ultrasound imaging.Documented coronary artery stenosis ≥ 50 % through peripheral vascular ultrasound imaging.
- Age >= 18 years
- Capacity to provide informed consent
Who cannot join
- Prior ischemic cardiac events (e.g., myocardial infarction, unstable angina).
- Major electrophysiological disorders.
- History of stroke or transient ischemic attack.
- Ongoing renal replacement therapy (dialysis).
- Use of systemic immunosuppressive or anti-inflammatory medications (beyond low-dose aspirin).
- Any chronic inflammatory or autoimmune disease.
Show all 17Show fewer
- Active infectious disease at the time of enrolment.
- Active malignancy or cancer treatment within the past 5 years.
- Coronary Artery Disease Group
- Prior ischemic cardiac events (e.g., myocardial infarction, unstable angina).
- Major electrophysiological disorders.
- History of stroke or transient ischemic attack.
- Ongoing renal replacement therapy (dialysis).
- Use of systemic immunosuppressive or anti-inflammatory medications (beyond low-dose aspirin).
- Any chronic inflammatory or autoimmune disease.
- Active infectious disease at the time of enrolment.
- Active malignancy or cancer treatment within the past 5 years.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Lazio, 00168
Giovanna Liuzzo, MD, PhD, +39 06 3015 6549, giovanna.liuzzo@policlinicogemelli.it
Francisco R Jimenez Trinidad, BSc, MSc, PhD, +39 06 3015 6621, franciscorafael.jimenez-trinidad@policlinicogemelli.it
About this study
Official title: Multilevel and Interdisciplinary Assessment of Subclinical to Clinical Atherosclerosis Interactions With Neurocognitive Function and Cardiovascular System Through Endothelial and Inflammatory Cell Signalling: The MISTIC Study
The MISTIC study is a non-profit, cross-sectional clinical research project aimed at investigating the relationship between atherosclerosis and both cardiovascular and cognitive function in adult populations.
Atherosclerosis is a progressive condition characterized by the accumulation of material within arterial walls, leading to vascular narrowing and impaired blood flow. While its most recognized consequences are acute events such as myocardial infarction or stroke, earlier stages of the disease, often asymptomatic, may already be associated with functional changes affecting multiple organ systems.
Read more
This study focuses on evaluating the association between vascular health and cognitive performance at a single time point. Atherosclerotic burden will be assessed using non-invasive imaging techniques, including carotid intima-media thickness and coronary calcium scoring. Cognitive performance will be measured using standardized neuropsychological tests.
Approximately 1000 participants will be enrolled and divided into two groups: a control group without clinically established cardiovascular disease, and a group of patients with coronary artery disease (CAD). All participants will undergo clinical evaluation, vascular imaging, cognitive testing, and analysis of biological samples.
The primary objective is to determine whether increasing atherosclerotic burden is associated with measurable differences in cognitive and cardiovascular function. Secondary aims include identifying patterns that may help improve early detection and risk stratification of vascular disease.
The results of this study are expected to contribute to a better understanding of atherosclerosis as a systemic condition and to support the development of preventive strategies targeting early stages of vascular disease.
- Being tested
- Peripheral Vascular Imaging, Coro-CT, Neurocognitive Assesment, Blood Sampling
- Keywords
- Atherosclerosis, Neurocognitive Decline, Inflammation
- Medical subject headings
- Atherosclerosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peripheral Vascular ImagingDiagnostic test
Peripheral Vascular Imaging of Carotid and Femoral Arteries by Eco-Doppler Ultrasound
Coro-CTDiagnostic test
Coronary Computed Axial Tomography (Coro-TC) with contrast administration
Neurocognitive AssesmentDiagnostic test
Study of neurocognitive function and decline by pre-established tests
Blood SamplingProcedure or surgery
Blood sampling for further molecular and cellular analysis
| Study group | Role | What they receive |
|---|---|---|
| Control Individuals | Not described Receives: Diagnostic Test: Peripheral Vascular Imaging; Diagnostic Test: Coro-CT; Diagnostic Test: Neurocognitive Assesment; Procedure: Blood Sampling | |
| Patients with Coronary Artery Disease | Not described Receives: Diagnostic Test: Peripheral Vascular Imaging; Diagnostic Test: Coro-CT; Diagnostic Test: Neurocognitive Assesment; Procedure: Blood Sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Carotid Intima-Media Thickness (cIMT) (mm)
The Carotid Intima-Media Thickness (cIMT) is a non-invasive ultrasound measurement used to assess the thickness of the inner two layers (intima and media) of the carotid artery wall. It is commonly used as a marker of subclinical atherosclerosis and cardiovascular risk.
The measurement is typically obtained from the common carotid artery using high-resolution B-mode ultrasound. Increased cIMT values are associated with a higher risk of cardiovascular events such as stroke and myocardial infarction.
cIMT is measured in millimeters (mm).
Measured: From enrollment to the end of diagnostic tests at 6 months
Agatston Score (RU)
The Agatston Score is a quantitative measure of coronary artery calcification obtained from non-contrast cardiac CT scans. It is used to estimate the burden of coronary atherosclerosis and predict the risk of future cardiovascular events.
The score is calculated by identifying areas of radiodense (hyperdense) calcium in the coronary arteries (attenuation ≥130 Hounsfield units), multiplying the area by a density factor, and summing the results across all coronary arteries.
The Agatston Score is expressed in Agatston Units (AU). It is a dimensionless index, not a physical unit, even though it is sometimes abbreviated as "RU" (risk units) in some contexts.
0 AU → no detectable calcification 1-99 AU → mild calcification 100-399 AU → moderate calcification
≥400 AU → extensive calcification
Measured: From enrollment to the end of treatment at 6 months
Montreal cognitive assessment (MoCA) test (points)
The Montreal Cognitive Assessment (MoCA) is a brief screening tool used to detect mild cognitive impairment and early dementia. It evaluates multiple cognitive domains, including: Attention and concentration, Executive functions, Memory (delayed recall), Language, Visuospatial skills, Abstraction and Orientation.
The test typically takes about 10 minutes to administer and consists of a series of short tasks (e.g., word recall, clock drawing, naming, and serial subtraction).
The MoCA is scored as a total point-based scale, with a maximum of 30 points. Scores are expressed simply as "points" (no physical units).
A score of 26 or above (≥26/30) is generally considered normal, although this may vary with age and education.
Measured: From enrollment to the end of treatment at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2026
- Study start1 May 2026 (estimated)
- Primary completion30 Apr 2030 (estimated)
- Study completion30 Apr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Subclinical Atherosclerotic Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 1,000 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liuzzo Giovanna, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07520643
- Sponsor's protocol ID
- 13671
- Acronym
- MISTIC
- Status last verified
- Apr 2026
- First submitted
- 26 Mar 2026
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Casolo G, Abrignani MG, Amico AF, Cademartiri F, Caporale R, Di Lenarda A, Domenicucci S, Gabrielli D, Geraci G, Indolfi C, Limbruno U, Midiri M, Murrone A, Musumeci G, Nardi F, Nistri S, Privitera C, Gulizia MM. [ANMCO/SIC/GISE/ARCA/SIRM Consensus document: Description of coronary atherosclerosis for diagnostic, prognostic and therapeutic purposes]. G Ital Cardiol (Rome). 2019 Jul-Aug;20(7):439-468. doi: 10.1714/3190.31688. Italian.
PubMed 31320766Tresch DD, Aronow WS. Clinical manifestations and diagnosis of coronary artery disease. Clin Geriatr Med. 1996 Feb;12(1):89-100.
PubMed 8653666Ajoolabady A, Pratico D, Lin L, Mantzoros CS, Bahijri S, Tuomilehto J, Ren J. Inflammation in atherosclerosis: pathophysiology and mechanisms. Cell Death Dis. 2024 Nov 11;15(11):817. doi: 10.1038/s41419-024-07166-8.
PubMed 39528464Gimbrone MA Jr, Garcia-Cardena G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301.
PubMed 26892962Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, Tokgozoglu L, Lewis EF. Atherosclerosis. Nat Rev Dis Primers. 2019 Aug 16;5(1):56. doi: 10.1038/s41572-019-0106-z.
PubMed 31420554
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multilevel and Interdisciplinary Assessment of Subclinical to Clinical Atherosclerosis Interactions With Neurocognitive Function and Cardiovascular System Through Endothelial and Inflammatory Cell Signalling: The MISTIC Study
- ClinicalTrials.gov ID
- NCT07520643
- Acronym / sponsor ID
- MISTIC / 13671
- Keywords
- Atherosclerosis, Neurocognitive Decline, Inflammation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 30 Apr 2030 (estimated)
- Study completion
- 30 Apr 2030 (estimated)
- First posted
- 9 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The MISTIC study is a non-profit, cross-sectional clinical research project aimed at investigating the relationship between atherosclerosis and both cardiovascular and cognitive function in adult populations.
Atherosclerosis is a progressive condition characterized by the accumulation of material within arterial walls, leading to vascular narrowing and impaired blood flow. While its most recognized consequences are acute events such as myocardial infarction or stroke, earlier stages of the disease, often asymptomatic, may already be associated with functional changes affecting multiple organ systems.
This study focuses on evaluating the association between vascular health and cognitive performance at a single time point. Atherosclerotic burden will be assessed using non-invasive imaging techniques, including carotid intima-media thickness and coronary calcium scoring. Cognitive performance will be measured using standardized neuropsychological tests.
Approximately 1000 participants will be enrolled and divided into two groups: a control group without clinically established cardiovascular disease, and a group of patients with coronary artery disease (CAD). All participants will undergo clinical evaluation, vascular imaging, cognitive testing, and analysis of biological samples.
The primary objective is to determine whether increasing atherosclerotic burden is associated with measurable differences in cognitive and cardiovascular function. Secondary aims include identifying patterns that may help improve early detection and risk stratification of vascular disease.
The results of this study are expected to contribute to a better understanding of atherosclerosis as a systemic condition and to support the development of preventive strategies targeting early stages of vascular disease.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Individuals | – | Diagnostic Test: Peripheral Vascular Imaging, Diagnostic Test: Coro-CT, Diagnostic Test: Neurocognitive Assesment, Procedure: Blood Sampling |
| Patients with Coronary Artery Disease | – | Diagnostic Test: Peripheral Vascular Imaging, Diagnostic Test: Coro-CT, Diagnostic Test: Neurocognitive Assesment, Procedure: Blood Sampling |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study includes 1000 participants recruited at Fondazione Policlinico Gemelli: 500 patients with advanced atherosclerosis undergoing PCI with ≥50% stenosis or documented coronary artery disease, and 500 control subjects from the Primary Cardiovascular Prevention Clinic with indications for CAC scoring, without prior acute coronary events. About 22% of controls may have subclinical atherosclerosis. Cognitive impairment is expected in 12-20% of patients and 4-10% of controls. All participants will undergo a single-timepoint assessment including clinical, imaging, molecular, and neurocognitive evaluations to study the association between vascular burden and cognitive function.
Key inclusion criteria (5 listed)
- Age >= 18 years
- Capacity to provide informed consent
- Documented coronary artery stenosis ≥ 50 % through peripheral vascular ultrasound imaging.Documented coronary artery stenosis ≥ 50 % through peripheral vascular ultrasound imaging.
- Age >= 18 years
- Capacity to provide informed consent
Key exclusion criteria (17 listed)
- Prior ischemic cardiac events (e.g., myocardial infarction, unstable angina).
- Major electrophysiological disorders.
- History of stroke or transient ischemic attack.
- Ongoing renal replacement therapy (dialysis).
- Use of systemic immunosuppressive or anti-inflammatory medications (beyond low-dose aspirin).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Peripheral Vascular ImagingPeripheral Vascular Imaging of Carotid and Femoral Arteries by Eco-Doppler Ultrasound | Diagnostic test | Control Individuals, Patients with Coronary Artery Disease |
| Coro-CTCoronary Computed Axial Tomography (Coro-TC) with contrast administration | Diagnostic test | Control Individuals, Patients with Coronary Artery Disease |
| Neurocognitive AssesmentStudy of neurocognitive function and decline by pre-established tests | Diagnostic test | Control Individuals, Patients with Coronary Artery Disease |
| Blood SamplingBlood sampling for further molecular and cellular analysis | Procedure or surgery | Control Individuals, Patients with Coronary Artery Disease |
Primary outcome
Carotid Intima-Media Thickness (cIMT) (mm)
Time frame: From enrollment to the end of diagnostic tests at 6 months
The Carotid Intima-Media Thickness (cIMT) is a non-invasive ultrasound measurement used to assess the thickness of the inner two layers (intima and media) of the carotid artery wall. It is commonly used as a marker of subclinical atherosclerosis and cardiovascular risk. The measurement is typically obtained from the common carotid artery using high-resolution B-mode ultrasound. Increased cIMT values are associated with a higher risk of cardiovascular events such as stroke and myocardial infarction. cIMT is measured in millimeters (mm).
Agatston Score (RU)
Time frame: From enrollment to the end of treatment at 6 months
The Agatston Score is a quantitative measure of coronary artery calcification obtained from non-contrast cardiac CT scans. It is used to estimate the burden of coronary atherosclerosis and predict the risk of future cardiovascular events. The score is calculated by identifying areas of radiodense (hyperdense) calcium in the coronary arteries (attenuation ≥130 Hounsfield units), multiplying the area by a density factor, and summing the results across all coronary arteries. The Agatston Score is expressed in Agatston Units (AU). It is a dimensionless index, not a physical unit, even though it is sometimes abbreviated as "RU" (risk units) in some contexts. 0 AU → no detectable calcification 1-99 AU → mild calcification 100-399 AU → moderate calcification ≥400 AU → extensive calcification
Montreal cognitive assessment (MoCA) test (points)
Time frame: From enrollment to the end of treatment at 6 months
The Montreal Cognitive Assessment (MoCA) is a brief screening tool used to detect mild cognitive impairment and early dementia. It evaluates multiple cognitive domains, including: Attention and concentration, Executive functions, Memory (delayed recall), Language, Visuospatial skills, Abstraction and Orientation. The test typically takes about 10 minutes to administer and consists of a series of short tasks (e.g., word recall, clock drawing, naming, and serial subtraction). The MoCA is scored as a total point-based scale, with a maximum of 30 points. Scores are expressed simply as "points" (no physical units). A score of 26 or above (≥26/30) is generally considered normal, although this may vary with age and education.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Background: PubMed 31320766Casolo G, Abrignani MG, Amico AF, Cademartiri F, Caporale R, Di Lenarda A, Domenicucci S, Gabrielli D, Geraci G, Indolfi C, Limbruno U, Midiri M, Murrone A, Musumeci G, Nardi F, Nistri S, Privitera C, Gulizia MM. [ANMCO/SIC/GISE/ARCA/SIRM Consensus document: Description of coronary atherosclerosis for diagnostic, prognostic and therapeutic purposes]. G Ital Cardiol (Rome). 2019 Jul-Aug;20(7):439-468. doi: 10.1714/3190.31688. Italian.
- Background: PubMed 8653666Tresch DD, Aronow WS. Clinical manifestations and diagnosis of coronary artery disease. Clin Geriatr Med. 1996 Feb;12(1):89-100.
- Background: PubMed 39528464Ajoolabady A, Pratico D, Lin L, Mantzoros CS, Bahijri S, Tuomilehto J, Ren J. Inflammation in atherosclerosis: pathophysiology and mechanisms. Cell Death Dis. 2024 Nov 11;15(11):817. doi: 10.1038/s41419-024-07166-8.
- Background: PubMed 26892962Gimbrone MA Jr, Garcia-Cardena G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301.
- Background: PubMed 31420554Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, Tokgozoglu L, Lewis EF. Atherosclerosis. Nat Rev Dis Primers. 2019 Aug 16;5(1):56. doi: 10.1038/s41572-019-0106-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Subclinical Atherosclerotic Cardiovascular Disease and Neurocognitive Decline, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Carotid Intima-Media Thickness (cIMT) (mm) (time frame: From enrollment to the end of diagnostic tests at 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07520643, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.