Heterozygous Familial Hypercholesterolemia (HeFH)DESTINY-FHNCT07427472
"Detection and Follow-up of Coronary Lesions in HeFH (DESTINY-FH Study)"
A study testing Coronary computed tomography angiography in people with Heterozygous Familial Hypercholesterolemia (HeFH), run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
Trial summary
This multicenter, non-randomized interventional study aims to assess coronary artery disease progression over 5 years in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH), using coronary computed tomography angiography (CCTA). Read more about this study
- Who is it for?
- Ages 30 to 60 years
- Conditions the study is for
- Heterozygous Familial Hypercholesterolemia (HeFH)
- What is being tested?
- Coronary computed tomography angiography
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 3 sitesFrance
- Study dates
- 19 Jun 2026to 19 Jun 2036
- Phase
- Interventional
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 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients with heterozygous familial hypercholesterolemia
- Aged 30 to 60 years.
- Patients who underwent a CAC score and a coronary CT angiogram at least 5 years ago, exclusively at the same imaging center (ICT de la Pitié Salpetrière).
- Patient asymptomatic for exertional chest pain at the time of CCTA
- Clinical examination performed
- Beneficiary of a social protection scheme or entitled person (excluding AME)
- Patient informed and consent form signed
Who cannot join
- Patient under guardianship, or unable to give consent
- Pregnancy, breast-feeding
- Technical contraindication: weight > 250 kg
- Simultaneous participation in other interventional research involving the human body, or period of exclusion following previous research involving the human body still in progress.
- Adults subject to a legal protection order
- Contraindication to esmolol and/or atenolol
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- Only for patients who need to undergo a CT angiogram and a thoraco-abdominal-pelvic CT scan:
- Renal insufficiency (LC<60)
- Unbalanced diabetes when acquiring a previous coronary angioscanner
- Personal history of cardiovascular disease and myocardial infarction at the time of CCTA
- Contraindication to iodinated contrast media
- Patient having already had an adverse event (AE) during the acquisition of a prior coronary angioscanner
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites, 3 recruiting
- Not yet recruiting
Plateau d'investigation clinique (PIC) IHU-ICAN
Paris, 75013
Silvia Angela BARRETTA, PhD, 01 84 827 7 63, s.barretta@ihuican.org
- Not yet recruiting
APHP- Hospital Saint-Antoine
Paris, Île-de-France Region, 75013
Franck BOCCARA, MD, PhD, 33(0)1 49 28 24 49, franck.boccara@aphp.fr
Franck BOCCARA, MD, PhD
- Recruiting
APHP-Sorbonne, Pitié Salpêtrière Hospital
Paris, Île-de-France Region, 75013
Antonio GALLO, MD, PhD, 33(0)1 42 17 57 74, antonio.gallo@aphp.fr
Antonio GALLO, MD, PhD
About this study
Official title: Detection and Longitudinal Follow-up of Non-calcified and Calcified Coronary Lesions in Heterozygous Familial Hypercholesterolemia (DESTINY-FH)
This multicenter, non-randomized interventional study aims to assess coronary artery disease progression over 5 years in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH), using coronary computed tomography angiography (CCTA).
The primary endpoint is the visual evaluation of coronary stenosis using CAD-RADS v2.0, identifying changes between baseline (2018-2022) and study inclusion. The study will enroll 300 patients (100 protected, 200 non-protected) from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Participation lasts up to one week. Total study duration is 2 years, with extended follow-up through routine care data over 10 years.
Read the detailed description
HeFH is an autosomal dominant genetic disorder characterized by lifelong elevated LDL-C levels, which significantly increase the risk of premature coronary atherosclerosis. Cardiovascular risk stratification in HeFH remains challenging due to limitations of traditional risk scores and stress testing. The coronary artery calcium (CAC) score is a useful tool for reclassifying cardiovascular risk but fails to detect non-calcified plaques, which may be prevalent in HeFH despite a CAC score of zero. Previous studies suggest a prevalence of non-calcified plaques as high as 30% in molecularly diagnosed HeFH patients.
This multicenter interventional, non-randomized comparative study aims to evaluate the progression of coronary artery disease over a 5-year period in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH). Using coronary computed tomography angiography (CCTA), the study will assess both calcified and non-calcified plaque burden in this high-risk population.
The primary outcome is the visual, semi-quantitative evaluation of coronary stenosis severity using CAD-RADS v2.0 classification to identify high-risk plaques and categorize patients as having regression, stability, or progression of coronary disease based on changes in CAD-RADS categories between baseline (2018-2022) and the DESTINY-FH study visit.
The study will enroll 300 patients (100 "protected" and 200 "non-protected") from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Individual participation will last from one day to one week. Total study duration is 2 years, with additional 10-year follow-up using routinely collected medical records.
- Being tested
- Coronary computed tomography angiography
- Keywords
- Coronary Artery Disease, Atherosclerosis, Coronary Plaque Vulnerability, Cardiovascular Risk, Cardiovascular Events
- Medical subject headings
- Coronary Artery Disease, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coronary computed tomography angiographyOther
Coronary computed tomography angiography with injection of iodinated contrast material
| Study group | Role | What they receive |
|---|---|---|
| Patients with protected and unprotected familial hypercholesterolemia | Other | Coronary computed tomography angiography with injection of iodinated contrast material Receives: Other: Coronary computed tomography angiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression of coronary artery disease over 5 years in patients with heterozygous familial hypercholesterolemia
The evolution of coronary artery disease will be assessed over 5 years in patients with heterozygous familial hypercholesterolemia using coronary CT angiography (CTA). The number of patients with regression, stability, or progression of coronary stenosis will be determined using semi-quantitative visual assessment of coronary stenoses according to the CAD-RADS v2.0 classification, including visual characterization of high-risk plaque features.Time Frame: 5 years Unit of Measure: Number and percentage of participants with regression, stability, or progression of coronary stenosis
Measured: 1 day
Secondary outcomes (38)
Change in total coronary plaque volume, lesion type, and proximal aortic calcifications.
Assessment of coronary artery disease progression in HeFH patients using 5-years follow-up CCTA. CAD-RADS v2.0 will be used to evaluate changes in stenosis severity and identify high-risk plaques. Progression will be defined by a change in CAD-RADS category between first CCTA (defined as baseline, realized between 2018 and 2022) and inclusion in DESTINY-FH
Measured: 1 day
Survival curve of major cardiovascular events incidence.
Incidence of myocardial infarction, ischemic stroke, transient ischemic attack, and coronary, carotid, and/or femoral revascularization since baseline CCTA in both groups
Measured: 1 day
Cox regression analysis of cardiovascular event occurrence and associated clinical, biological, and omics data.
Evaluation of the association between cardiovascular event occurrence (as defined in outcome 2) and clinical, biological, omics, and macro/microvascular data using Cox regression analysis.
Measured: 1 day
Linear regression of clinical and biological variables by CAD-RADS category change.
Comparison and linear regression of clinical and biological explanatory variables according to change in CAD-RADS category between baseline and inclusion, in the overall cohort and stratified by groups.
Measured: 1 day
Comparison of omics data by plaque volume change and CAD-RADS category shift.
Comparison of omics data based on the quantitative change in total coronary plaque volume or change in CAD-RADS category between baseline and inclusion, stratified by group.
Measured: 1 day
Baseline prevalence of carotid plaque by group
Presence or absence of carotid plaque will be assessed at baseline using coronary CT angiography (CTA). Prevalence of carotid plaque will be compared between groups at baseline.
Unit of Measure:
% of participants with carotid plaque
Measured: 1 day
Baseline prevalence of femoral plaque by group
Presence or absence of femoral plaque will be assessed at baseline using duplex Doppler ultrasound. Prevalence of femoral plaque will be compared between groups at baseline.
Unit of Measure:% of participants with femoral plaque
Measured: 1 day
Baseline aortic valve calcium score by group
Aortic valve calcium score will be measured at baseline using non-contrast cardiac CT according to the Agatston method. Scores will be compared between groups at baseline.
Unit of Measure:Agatston score (Agatston units)
Measured: 1 day
Baseline thoracic aorta calcium score by group
Thoracic aorta calcium score will be measured at baseline using non-contrast cardiac CT according to the Agatston method. Scores will be compared between groups at baseline.
Unit of Measure:Agatston score (Agatston units)
Measured: 1 day
Baseline diameters of the ascending and descending aorta by group
Aortic diameters will be measured at baseline using CT angiography (mm). Measurements will be compared between groups at baseline. Unit of Measure: Aortic diameter (mm).
Measured: 1 day
Correlation between baseline carotid plaque presence and change in coronary plaque volume
Presence or absence of carotid plaque will be assessed at baseline using duplex Doppler ultrasound. Its correlation with change in total coronary plaque volume between baseline and follow-up will be evaluated. Coronary plaque volume will be quantified using coronary CT angiography (CTA).
Unit of Measure:Change in coronary plaque volume (mm³)
Measured: Baseline to 5 years
Correlation between baseline femoral plaque presence and change in coronary plaque volume
Presence or absence of femoral plaque will be assessed at baseline using duplex Doppler ultrasound. Its correlation with change in total coronary plaque volume between baseline and follow-up will be evaluated. Coronary plaque volume will be quantified using coronary CT angiography (CTA).
Unit of Measure:
Change in coronary plaque volume (mm³)
Measured: Baseline to 5 years
Correlation between baseline CAC score (aortic valve and thoracic aorta) and coronary plaque progression
Coronary artery calcium (CAC) score will be measured at baseline using non-contrast CT (Agatston method). The CAC score of the aortic valve and thoracic aorta will be correlated with change in total coronary plaque volume (mm³) and CAD-RADS category between baseline and follow-up, as assessed by CTA.
Unit of Measure: CAC score (Agatston units); change in coronary plaque volume (mm³); change in CAD-RADS category.
Measured: 1 day
Correlation between baseline aortic diameters and coronary plaque progression
Aortic diameters (ascending and thoracic aorta) will be measured at baseline using CT angiography (mm). Aortic diameter values will be correlated with change in total coronary plaque volume (mm³) and plaque vulnerability features on coronary CTA between baseline and follow-up.
Unit of Measure: Aortic diameter (mm); change in coronary plaque volume (mm³).
Measured: 1 day
Baseline epicardial fat volume by group
Epicardial fat volume will be measured at baseline using coronary CT angiography (CTA). Volumes will be compared between groups at baseline.
Unit of Measure: Epicardial fat volume (cm³)
Measured: 1 day
Baseline epicardial fat density by group
Epicardial fat density will be measured at baseline using coronary CT angiography (CTA). Density will be compared between groups at baseline.
Unit of Measure: Epicardial fat density (Hounsfield Units, HU)
Measured: 1 day
Baseline subdiaphragmatic abdominal adipose tissue volume at L1 by group
Subdiaphragmatic abdominal adipose tissue volume will be quantified at the level of the first lumbar vertebra (L1) using non-contrast CT. Segmentation will be performed using standard attenuation thresholds for adipose tissue. Relative adipose tissue volume will be compared between groups at baseline.
Unit of Measure:Relative adipose tissue volume (%)
Measured: 1 day
Baseline subdiaphragmatic abdominal adipose tissue density at L1 by group
Mean attenuation of subdiaphragmatic abdominal adipose tissue will be measured at the level of L1 using non-contrast CT. Mean density will be compared between groups at baseline.
Unit of Measure:Mean adipose tissue density (Hounsfield Units, HU)
Measured: 1 day
Baseline arterial wall thickness by group
Arterial wall thickness will be measured at baseline using adaptive optics retinal imaging. Values will be compared between groups at baseline.
Unit of Measure: Wall thickness (µm).
Measured: 1 day
Baseline arterial lumen diameter by group
Arterial lumen diameter will be measured at baseline using adaptive optics retinal imaging. Values will be compared between groups at baseline.
Unit of Measure: Lumen diameter (µm).
Measured: 1 day
Baseline arterial wall-to-lumen ratio by group
Wall-to-lumen ratio will be calculated at baseline using adaptive optics retinal imaging. Ratios will be compared between groups at baseline.
Unit of Measure: Wall-to-lumen ratio (unitless).
Measured: 1 day
Baseline arterial wall cross-sectional area by group
Arterial wall cross-sectional area will be measured at baseline using adaptive optics retinal imaging. Values will be compared between groups at baseline.
Unit of Measure: wall cross-sectional area (µm²).
Measured: 1 day
Correlation between retinal arterial wall thickness and coronary plaque progression
Arterial wall thickness will be measured at baseline using adaptive optics retinal imaging. Its correlation with change in total coronary plaque volume (mm³) and CAD-RADS category between baseline and follow-up will be evaluated.Unit of Measure: Wall thickness (µm); change in coronary plaque volume (mm³); CAD-RADS category
Measured: 1 day
Correlation between retinal lumen diameter and coronary plaque progression
Arterial lumen diameter will be measured at baseline using adaptive optics retinal imaging. Its correlation with change in total coronary plaque volume (mm³) and CAD-RADS category between baseline and follow-up will be evaluated.
Unit of Measure: Lumen diameter (µm); change in coronary plaque volume (mm³); CAD-RADS category.
Measured: 1 day
Correlation between retinal wall-to-lumen ratio and coronary plaque progression
Wall-to-lumen ratio will be measured at baseline using adaptive optics retinal imaging. Its correlation with change in total coronary plaque volume (mm³) and CAD-RADS category between baseline and follow-up will be evaluated.
Unit of Measure: Wall-to-lumen ratio (unitless); change in coronary plaque volume (mm³); CAD-RADS category
Measured: 1 day
Correlation between retinal arterial wall cross-sectional area and coronary plaque progression
Arterial wall cross-sectional area will be measured at baseline using adaptive optics retinal imaging. Its correlation with change in total coronary plaque volume (mm³) and CAD-RADS category between baseline and follow-up will be evaluated.
Unit of Measure: Cross-sectional area (mm²); change in coronary plaque volume (mm³); CAD-RADS category
Measured: 1 day
Comparison of liver and spleen density at baseline between groups
Comparison of unenhanced liver and spleen density between groups at baseline.
Measured: 1 day
Gut microbiota composition at baseline using metabolomics and metagenomics.
Characterization of gut microbiota at baseline in both groups using targeted and untargeted metabolomics (e.g., secondary bile acids, choline/tryptophan/cholesterol derivatives, short-chain fatty acids) and metagenomic sequencing with bioinformatic analysis of bacterial populations.
Measured: 1 day
Association between baseline omics data and coronary plaque progression.
Comparison of baseline omics data according to the change in total coronary plaque volume or CAD-RADS category between baseline and inclusion, stratified by group.
Measured: 1 day
Change in gut microbiota composition between baseline and inclusion
Comparison of gut microbiota composition between baseline (for patients previously included in the FHCALC study) and inclusion, in both groups
Measured: 1 day
Comparison of arterial stiffness at baseline between groups.
Comparison of arterial stiffness measurements between groups at baseline.
Measured: 1 day
SF-36 Health Survey score at inclusion
The SF-36 Health Survey will be administered at inclusion. The total score and domain scores will be recorded, ranging from 0 to 100, where higher scores indicate better health status.
Unit of Measure: Score (0-100)
Measured: 1 day
Seattle Angina Questionnaire-7 (SAQ-7) score at inclusion
The SAQ-7 will be administered at inclusion. Scores range from 0 to 100, with higher scores indicating less angina and better functional status.
Unit of Measure: Score (0-100)
Measured: 1 day
Rose Dyspnea Scale score at inclusion
The Rose Dyspnea Scale will be administered at inclusion. Scores range from 0 to 4, where higher scores indicate greater breathlessness.
Unit of Measure: Score (0-4)
Measured: 1 day
Patient Health Questionnaire-2 (PHQ-2) score at inclusion
The PHQ-2 will be administered at inclusion. Scores range from 0 to 6, with higher scores indicating greater depressive symptoms.
Unit of Measure: Score (0-6)
Measured: 1 day
Hospital Anxiety and Depression Scale (HADS) score at inclusion
The HADS will be administered at inclusion. Scores range from 0 to 21 for anxiety and 0 to 21 for depression, with higher scores indicating greater symptom severity.
Unit of Measure: Score (0-21) for anxiety; Score (0-21) for depression
Measured: 1 day
CONSTANCES study questionnaire scores at inclusion
Selected standardized questionnaires from the CONSTANCES cohort study will be administered at inclusion. Scores will be recorded according to the original scoring system of each questionnaire (specific scales and units to be defined).
Unit of Measure: As per original scoring system of each CONSTANCES questionnaire
Measured: 1 day
Incidence of major cardiovascular events at 5 and 10 years
Occurrence of major cardiovascular events-including myocardial infarction, ischemic stroke, transient ischemic attack (TIA), and coronary, carotid, and/or femoral revascularization-will be recorded. Events will be ascertained through clinical records and patient interviews. Survival curves will be generated to estimate cumulative incidence at both 5- and 10-year follow-up.
Measured: 5 and 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2026
- Study start19 Jun 2026
- Primary completion19 Jun 2028 (estimated)
- Study completion19 Jun 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heterozygous Familial Hypercholesterolemia (HeFH)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Biology: Specific omic biology (including metabolomics, lipidomics, proteomics, genetics, inflammation, and metagenomics). Imaging: Coronary computed tomography angiography with injection of iodinated contrast material DEXA scan Fibroscan Non-invasive vascular assessment of the fundus using adaptive optics Other: Measurement of arterial stiffness Injection of esmolol or atenolol only for patients with a heart rate \>65 bpm.
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07427472
- Sponsor's protocol ID
- APHP250574
- Acronym
- DESTINY-FH
- Status last verified
- Jun 2026
- First submitted
- 14 Aug 2025
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations