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Clinical Transfer of a Vulnerable Atherosclerotic Plaque Tracer : 99mTc-cAbVCAM1-5 (ATHENA) (ATHENA)

Primary Purpose

Cardiovascular Diseases, Atherosclerosis

Status
Active
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
99mTccAbVCAM1-5 injection
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Cardiovascular Diseases focused on measuring 99mTc-cAbVCAM1-5, intravenous injection

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy volunteers:

  1. Ages 18-55
  2. No nuclear imaging or CT scans in the year prior to inclusion
  3. A person not exposed to ionizing radiation according to the labour code.

Patients:

  1. Ages between 18 and 80
  2. Atherosclerosis with asymptomatic carotid atheroma plate.

  3. Indication of carotid endarterectomy.

    All:

  4. Person affiliated with or benefiting from social security
  5. Person who has given written informed consent

Non inclusion Criteria:

  1. Woman of childbearing potential in the absence of highly effective contraception or man of childbearing potential without mechanical contraception.
  2. Medical history that significantly interferes with biodistribution
  3. History of disease which may impair the absorption, diffusion and excretion of the radiopharmaceutical: Crohn's disease, celiac disease.
  4. Known allergy to one of the constituents of the product.
  5. Intoxication with alcohol or drugs on purpose
  6. Grade 3 haematological toxicity for the following parameters : Hemoglobin, platelets, leukocytes and neutrophil polynuclear cells.
  7. 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.
  8. Grade 2 liver toxicity for the following parameters : AST, ALT, GGT, PAL and bilirubin.
  9. Grade 2 pancreatic toxicity for the following parameter: lipase.
  10. Blood or urine pregnancy test (confirmed in blood) inconclusive or positive for women of childbearing potential.
  11. Participation in other research involving the type 1 or 2 human being at the same time
  12. Person in a period of exclusion from other research involving the human person
  13. Living conditions suggesting an inability to follow all the visits provided for in the protocol.
  14. 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.
  15. Subject not contactable in case of emergency
  16. Protected person (Sections L1121-5 to L1121-8 of the CSP)

Sites / Locations

  • Grenoble Alpes University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

99mTccAbVCAM1-5

Arm Description

Healthy volunteers and asymptomatic patients Pré-screening of the volunteers by the CIC or the Vascular Surgeon and sending or handing over the newsletter Visit 0 Selection: Validation of IC / NIC + Consent collection + additional exams Visit 1 Inclusion: J0 Scintigraphic imaging following injection 99mTc-cAbVCAM1-5 (370 MBq - 550 MBq - 750 MBq depend of the SAE or AE ) Visit 2: Follow-up visit (Day 14 +/- 7 days post injection) Visit 3: End of the study, follow-up visit (70 days +/- 10 days post injection)

Outcomes

Primary Outcome Measures

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.
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Total Cholesterol (g/L)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Liver enzymes (ASAT - ALAT - GGT)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Total bilirubin
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by Electrocardiogram.
ECG (P Wave, QRS Complex, QT Interval)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Blood preasure (mmHg)
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Heart rate (beats/min)

Secondary Outcome Measures

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
Dosimetry evaluation of 99mTc-cAbVCAM1-5 in healthy volunteers and patients.
Dosimetry mesured in healthy subjects and patients in the different organs
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.

Full Information

First Posted
March 9, 2020
Last Updated
May 22, 2023
Sponsor
University Hospital, Grenoble
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1. Study Identification

Unique Protocol Identification Number
NCT04483167
Brief Title
Clinical Transfer of a Vulnerable Atherosclerotic Plaque Tracer : 99mTc-cAbVCAM1-5 (ATHENA)
Acronym
ATHENA
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 15, 2020 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Atherosclerosis
Keywords
99mTc-cAbVCAM1-5, intravenous injection

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
7 healthy volunteers (1+3+3) and 6 asymptomatic patients
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
99mTccAbVCAM1-5
Arm Type
Experimental
Arm Description
Healthy volunteers and asymptomatic patients Pré-screening of the volunteers by the CIC or the Vascular Surgeon and sending or handing over the newsletter Visit 0 Selection: Validation of IC / NIC + Consent collection + additional exams Visit 1 Inclusion: J0 Scintigraphic imaging following injection 99mTc-cAbVCAM1-5 (370 MBq - 550 MBq - 750 MBq depend of the SAE or AE ) Visit 2: Follow-up visit (Day 14 +/- 7 days post injection) Visit 3: End of the study, follow-up visit (70 days +/- 10 days post injection)
Intervention Type
Drug
Intervention Name(s)
99mTccAbVCAM1-5 injection
Intervention Description
intravenous injection of 99mTccAbVCAM1-5 with dose increase
Primary Outcome Measure Information:
Title
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.
Description
All Adverse events reported according to 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
Title
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Description
Total Cholesterol (g/L)
Time Frame
24 hours for healthy volonteers, 6 hours for patients.
Title
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Description
Liver enzymes (ASAT - ALAT - GGT)
Time Frame
24 hours for healthy volonteers, 6 hours for patients.
Title
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by biological parameters.
Description
Total bilirubin
Time Frame
24 hours for healthy volonteers, 6 hours for patients.
Title
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by Electrocardiogram.
Description
ECG (P Wave, QRS Complex, QT Interval)
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
Title
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Description
Blood preasure (mmHg)
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
Title
Evaluation of 99mTc-cAbVCAM1-5 adverse events as assessed by vital signs.
Description
Heart rate (beats/min)
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
Secondary Outcome Measure Information:
Title
Assessment of biodistribution in all subjects included in the study (healthy volunteers + patients)
Description
Radioactive activity (MBq) measured in urine, blood and stool + full body images
Time Frame
24 hours for healthy volonteers, 6 hours for patients.
Title
Dosimetry evaluation of 99mTc-cAbVCAM1-5 in healthy volunteers and patients.
Description
Dosimetry mesured in healthy subjects and patients in the different organs
Time Frame
24 hours for healthy volonteers, 6 hours for patients.
Title
Evaluation of the feasibility of the technique using 99mTccAbVCAM1-5 as a tracer for the vulnerable atheroma plate.
Description
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.
Time Frame
3 hours after injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas DE LEIRIS
Organizational Affiliation
Grenoble Alpes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Grenoble Alpes University Hospital
City
Grenoble
ZIP/Postal Code
38043
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28919116
Citation
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. Erratum In: Lancet. 2017 Oct 28;390(10106):e38.
Results Reference
background
PubMed Identifier
3180375
Citation
Little 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.
Results Reference
background

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Clinical Transfer of a Vulnerable Atherosclerotic Plaque Tracer : 99mTc-cAbVCAM1-5 (ATHENA)

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