Cardiovascular DiseasesPhase 1ATHENANCT04483167
Clinical Transfer of a Vulnerable Atherosclerotic Plaque Tracer : 99mTc-cAbVCAM1-5 (ATHENA)
A Phase 1 study testing 99mTccAbVCAM1-5 injection in people with Cardiovascular Diseases and Atherosclerosis, run by University Hospital, Grenoble at 1 site in France.
Trial summary
Clinical Transfer of a Tracer of the Vulnerable Atheroma Plate: 99mTc-cAbVCAM1-5. (ATHENA). This is a phase I/IIa, prospective, monocentric, non-controlled, non-randomized, open-label, interventional study. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Atherosclerosis
- What is being tested?
- 99mTccAbVCAM1-5 injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteFrance
- Study dates
- 15 Sep 2020to May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers:
- Ages 18-55
- No nuclear imaging or CT scans in the year prior to inclusion
- A person not exposed to ionizing radiation according to the labour code.
- Patients:
- Ages between 18 and 80
Show all 28Show fewer
- Atherosclerosis with asymptomatic carotid atheroma plate.
- Indication of carotid endarterectomy.
- All:
- Person affiliated with or benefiting from social security
- Person who has given written informed consent
- Non inclusion Criteria:
- Woman of childbearing potential in the absence of highly effective contraception or man of childbearing potential without mechanical contraception.
- Medical history that significantly interferes with biodistribution
- History of disease which may impair the absorption, diffusion and excretion of the radiopharmaceutical: Crohn's disease, celiac disease.
- Known allergy to one of the constituents of the product.
- Intoxication with alcohol or drugs on purpose
- Grade 3 haematological toxicity for the following parameters : Hemoglobin, platelets, leukocytes and neutrophil polynuclear cells.
- Grade 2 renal toxicity for the following parameters: Urea and creatinine and/or Glomerular filtration rate according to the CPK-EPI formula < 60mL/min/1.73m².
- Grade 2 liver toxicity for the following parameters : AST, ALT, GGT, PAL and bilirubin.
- Grade 2 pancreatic toxicity for the following parameter: lipase.
- Blood or urine pregnancy test (confirmed in blood) inconclusive or positive for women of childbearing potential.
- Participation in other research involving the type 1 or 2 human being at the same time
- Person in a period of exclusion from other research involving the human person
- Living conditions suggesting an inability to follow all the visits provided for in the protocol.
- Subject who would receive more than 4,500 euros in compensation as a result of participation in other research involving the human person in the 12 months preceding this study.
- Subject not contactable in case of emergency
- Protected person (Sections L1121-5 to L1121-8 of the CSP)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study, Prospective, Monocentric, Uncontrolled, Non-randomized, Open, Interventional. First Human Administration of an Inflammation Tracer (99mTc-cAbVCAM1-5) Using the Scintigraphy in Healthy Volunteers and Asymptomatic Patients.
Clinical Transfer of a Tracer of the Vulnerable Atheroma Plate: 99mTc-cAbVCAM1-5. (ATHENA).
This is a phase I/IIa, prospective, monocentric, non-controlled, non-randomized, open-label, interventional study.
Read the detailed description
Cardiovascular disease (CVD) is the leading cause of death worldwide with more than 17.6 million deaths. Of these 17.6 millions deaths, 15 millions (85.1%) are attributable to coronary heart disease and cerebrovascular disease, and in both cases the main etiology is atherosclerosis.
In the coronary arteries, while the presence of a stenosing atherosclerotic plate can be detected by the coronary angiography technique that allows visualization of the lumen of the vessels, the same cannot be said of a plate that is vulnerable to eccentric remodeling. Indeed, this plate has little or no effect on the lumen of the artery. As a result, it is undetectable on coronary angiography. These vulnerable coronary atheromatous plaques are characterized by intense inflammatory phenomena leading to the formation of a large lipidic and necrotic heart covered by a thin fibrous capsule. They are prone to rupture, with the immediate consequence of the formation of a thrombus that can cause ischemia and necrosis of the downstream myocardial territory. In practice, 68% of myocardial infarctions are caused by the rupture of vulnerable plaques resulting in stenosis of less than 50% of the vascular lumen. In addition, in two-thirds of cases the infarction is the inaugural clinical event of coronary artery disease.
Currently, there are no validated non-invasive techniques for diagnosing vulnerable atheroma plate. In this context, the Laboratory Radiopharmaceutiques Biocliniques (LRB, UMR_S1039), has selected Vascular Cell Adhesion Molecule 1 (VCAM-1) as a potential target for molecular imaging of vulnerable plate. Indeed, in the arterial tree, its expression is restricted to atheromatous plates presenting an inflammatory phenotype which is considered a major vulnerability criterion. A radiopharmaceutical targeting VCAM-1 (99mTccAbVCAM1-5) has therefore been developed and validated in preclinical studies.
The final objective of this project is to evaluate in clinical practice the potential of this new imaging agent for the non invasive diagnosis of the vulnerable atheroma plates.
- Conditions
- Cardiovascular Diseases, Atherosclerosis
- Being tested
- 99mTccAbVCAM1-5 injection
- Keywords
- 99mTc-cAbVCAM1-5, intravenous injection
- Medical subject headings
- Cardiovascular Diseases, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
99mTccAbVCAM1-5 injectionDrug
intravenous injection of 99mTccAbVCAM1-5 with dose increase
| Study group | Role | What they receive |
|---|---|---|
| 99mTccAbVCAM1-5 | Experimental | Healthy volunteers and asymptomatic patients
1. Pré-screening of the volunteers by the CIC or the Vascular Surgeon and sending or handing over the newsletter
2. Visit 0 Selection: Validation of IC / NIC + Consent collection + additional exams
3. Visit 1 Inclusion: J0 Scintigraphic imaging following injection 99mTc-cAbVCAM1-5 (370 MBq - 550 MBq - 750 MBq depend of the SAE or AE )
4. Visit 2: Follow-up visit (Day 14 +/- 7 days post injection)
5. Visit 3: End of the study, follow-up visit (70 days +/- 10 days post injection) Receives: Drug: 99mTccAbVCAM1-5 injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by all adverse event according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.
All Adverse events reported according to according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.
Measured: 70 days after IP injection +/- 10 days
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Total Cholesterol (g/L)
Measured: 24 hours for healthy volonteers, 6 hours for patients.
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Liver enzymes (ASAT - ALAT - GGT)
Measured: 24 hours for healthy volonteers, 6 hours for patients.
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Total bilirubin
Measured: 24 hours for healthy volonteers, 6 hours for patients.
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by Electrocardiogram.
ECG (P Wave, QRS Complex, QT Interval)
Measured: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Blood preasure (mmHg)
Measured: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Heart rate (beats/min)
Measured: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
Secondary outcomes (3)
Assessment of biodistribution in all subjects included in the study (healthy volunteers + patients)
Radioactive activity (MBq) measured in urine, blood and stool + full body images
Measured: 24 hours for healthy volonteers, 6 hours for patients.
Dosimetry evaluation of 99mTc-cAbVCAM1-5 in healthy volunteers and patients.
Dosimetry mesured in healthy subjects and patients in the different organs
Measured: 24 hours for healthy volonteers, 6 hours for patients.
Evaluation of the feasibility of the technique using 99mTccAbVCAM1-5 as a tracer for the vulnerable atheroma plate.
Verification of the concordance between the expression of VCAM-1 in imaging and on operative part of carotid endarterectomy in patients. Comparison between the intensity of the 99mTc-cAbVCAM1-5 signal observed at the level of the carotids and the level of expression of VCAM-1 determined on an operative endarterectomy part of the carotid concerned, by immunohistochemistry and / or ELISA assay.
Measured: 3 hours after injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2020
- Study start15 Sep 2020
- Primary completionMay 2023 (estimated)
- Study completionMay 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 7 healthy volunteers (1+3+3) and 6 asymptomatic patients
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas DE LEIRIS, Principal investigator, Grenoble Alpes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04483167
- Sponsor's protocol ID
- 38RC19.051
- Acronym
- ATHENA
- Status last verified
- May 2023
- First submitted
- 9 Mar 2020
- Last updated
- 23 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1151-1210. doi: 10.1016/S0140-6736(17)32152-9.
PubMed 28919116Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988 Nov;78(5 Pt 1):1157-66. doi: 10.1161/01.cir.78.5.1157.
PubMed 3180375
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study, Prospective, Monocentric, Uncontrolled, Non-randomized, Open, Interventional. First Human Administration of an Inflammation Tracer (99mTc-cAbVCAM1-5) Using the Scintigraphy in Healthy Volunteers and Asymptomatic Patients.
- ClinicalTrials.gov ID
- NCT04483167
- Acronym / sponsor ID
- ATHENA / 38RC19.051
- Conditions
- Cardiovascular Diseases, Atherosclerosis
- Keywords
- 99mTc-cAbVCAM1-5, intravenous injection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 15 Sep 2020 (actual)
- Primary completion
- May 2023 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 23 Jul 2020 (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.
Clinical Transfer of a Tracer of the Vulnerable Atheroma Plate: 99mTc-cAbVCAM1-5. (ATHENA).
This is a phase I/IIa, prospective, monocentric, non-controlled, non-randomized, open-label, interventional study.
Detailed description
Cardiovascular disease (CVD) is the leading cause of death worldwide with more than 17.6 million deaths. Of these 17.6 millions deaths, 15 millions (85.1%) are attributable to coronary heart disease and cerebrovascular disease, and in both cases the main etiology is atherosclerosis.
In the coronary arteries, while the presence of a stenosing atherosclerotic plate can be detected by the coronary angiography technique that allows visualization of the lumen of the vessels, the same cannot be said of a plate that is vulnerable to eccentric remodeling. Indeed, this plate has little or no effect on the lumen of the artery. As a result, it is undetectable on coronary angiography. These vulnerable coronary atheromatous plaques are characterized by intense inflammatory phenomena leading to the formation of a large lipidic and necrotic heart covered by a thin fibrous capsule. They are prone to rupture, with the immediate consequence of the formation of a thrombus that can cause ischemia and necrosis of the downstream myocardial territory. In practice, 68% of myocardial infarctions are caused by the rupture of vulnerable plaques resulting in stenosis of less than 50% of the vascular lumen. In addition, in two-thirds of cases the infarction is the inaugural clinical event of coronary artery disease.
Currently, there are no validated non-invasive techniques for diagnosing vulnerable atheroma plate. In this context, the Laboratory Radiopharmaceutiques Biocliniques (LRB, UMR_S1039), has selected Vascular Cell Adhesion Molecule 1 (VCAM-1) as a potential target for molecular imaging of vulnerable plate. Indeed, in the arterial tree, its expression is restricted to atheromatous plates presenting an inflammatory phenotype which is considered a major vulnerability criterion. A radiopharmaceutical targeting VCAM-1 (99mTccAbVCAM1-5) has therefore been developed and validated in preclinical studies.
The final objective of this project is to evaluate in clinical practice the potential of this new imaging agent for the non invasive diagnosis of the vulnerable atheroma plates.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 7 healthy volunteers (1+3+3) and 6 asymptomatic patients
| Arm | Type | Receives |
|---|---|---|
| 99mTccAbVCAM1-5 | Experimental | Drug: 99mTccAbVCAM1-5 injectionHealthy volunteers and asymptomatic patients 1. Pré-screening of the volunteers by the CIC or the Vascular Surgeon and sending or handing over the newsletter 2. Visit 0 Selection: Validation of IC / NIC + Consent collection + additional exams 3. Visit 1 Inclusion: J0 Scintigraphic imaging following injection 99mTc-cAbVCAM1-5 (370 MBq - 550 MBq - 750 MBq depend of the SAE or AE ) 4. Visit 2: Follow-up visit (Day 14 +/- 7 days post injection) 5. Visit 3: End of the study, follow-up visit (70 days +/- 10 days post injection) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Ages 18-55
- No nuclear imaging or CT scans in the year prior to inclusion
- A person not exposed to ionizing radiation according to the labour code.
- Ages between 18 and 80
- Atherosclerosis with asymptomatic carotid atheroma plate.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| 99mTccAbVCAM1-5 injectionintravenous injection of 99mTccAbVCAM1-5 with dose increase | Drug | 99mTccAbVCAM1-5 |
Primary outcome
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by all adverse event according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.
Time frame: 70 days after IP injection +/- 10 days
All Adverse events reported according to according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27.
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Time frame: 24 hours for healthy volonteers, 6 hours for patients.
Total Cholesterol (g/L)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Time frame: 24 hours for healthy volonteers, 6 hours for patients.
Liver enzymes (ASAT - ALAT - GGT)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Time frame: 24 hours for healthy volonteers, 6 hours for patients.
Total bilirubin
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by Electrocardiogram.
Time frame: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
ECG (P Wave, QRS Complex, QT Interval)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Time frame: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
Blood preasure (mmHg)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Time frame: 24 hours for healthy volonteers, 6 hours for patients and 14 days after IP injection +/- 7 days + 70 days after IP injection for each group
Heart rate (beats/min)
3 secondary outcomes
Assessment of biodistribution in all subjects included in the study (healthy volunteers + patients)
Time frame: 24 hours for healthy volonteers, 6 hours for patients.
Dosimetry evaluation of 99mTc-cAbVCAM1-5 in healthy volunteers and patients.
Time frame: 24 hours for healthy volonteers, 6 hours for patients.
Evaluation of the feasibility of the technique using 99mTccAbVCAM1-5 as a tracer for the vulnerable atheroma plate.
Time frame: 3 hours after injection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
- Background: PubMed 28919116GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1151-1210. doi: 10.1016/S0140-6736(17)32152-9.
- Background: PubMed 3180375Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988 Nov;78(5 Pt 1):1157-66. doi: 10.1161/01.cir.78.5.1157.
- 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. This study is not recruiting at the moment.
Nicolas DE LEIRIS principal investigator
Grenoble Alpes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 99mTccAbVCAM1-5 injection in people with Cardiovascular Diseases and Atherosclerosis, run by University Hospital, Grenoble at 1 site in France.
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 28 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 23 May 2023. 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 France. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by all adverse event according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)_v5.0_2017-11-27. (time frame: 70 days after IP injection +/- 10 days). The study lists 7 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 NCT04483167, which also lists 2 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 23 May 2023.