68Ga-DOTATATE PET-CTA Imaging for the Early Detection of Progressing Coronary Atherosclerosis (iPROGRESS)

Assistance Publique - Hôpitaux de Paris

Status and phase

Terminated

Phase 3

Conditions

Coronary Arteriosclerosis

Treatments

Drug: injection of 68Ga-DOTATATE

Study type

Interventional

Funder types

Other

Identifiers

NCT04043377

2017-004793-34 (EudraCT Number)

P 171103

Details and patient eligibility

About

68Ga-DOTATATE is a PET radiotracer with high affinity and selectivity for somatostatin receptor 2 (SSTR 2) and is approved clinically for the evaluation of patients with neuroendocrine tumors. The SSTR2 receptor is also highly expressed at the surface of human macrophages and lymphocytes. In comparison to FDG, 68Ga-DOTATATE presents the advantage of fast clearance from tissues, which are not expressing somatostatin receptors, in particular muscular and myocardial tissues, and the level of blood glucose does not influence its uptake.

Accumulation of 68Ga-DOTATATE has already been detected in coronary and carotid plaques and is associated with the number of activated macrophages present in plaques obtained after carotid endarterectomy. In a recent study, Tarkin et al. confirmed the preferential uptake of 68Ga-DOTATATE by macrophages in atherosclerotic plaques. In addition, the intensity of 68Ga-DOTATATE was higher in culprit lesions in the carotid and coronary arteries than in stable lesions. The evaluation of 68Ga-DOTATATE uptake in coronary arteries was also strongly facilitated in comparison to FDG thanks to the absence of spillover signal from the myocardium.

AAA has developed a new kit that has markedly simplified the synthesis of 68Ga-DOTATATE and has obtained in the US marketing authorization for the kit (Netspot; kit for the preparation of Gallium-68-DOTATATE injection for intravenous use) on June 1st 2016 (NDA 208547) for evaluation of patients with neuro-endocrine tumors. The Netspot kit will be used in this study for the detection of progressing coronary atherosclerosis.

Full description

Design of the trial :

iPROGRESS is a prospective interventional study. The primary objective of this study will be to test the association between the intensity of 68Ga-DOTATATE uptake in coronary plaques quantified with PET at M0 and the absolute progression rate of coronary artery calcium scoring (CACS) measured between the CT acquired at M0 and after 2 years.

Patients will be screened until 1 month before the inclusion (M0) visit. Thereafter, 3 visits specifics to the study will be performed.

M0 (baseline): Injection of 68Ga-DOTATATE followed by PET-scan and a CCTA-scan M12 et M24(follow-up): Consultation and low-dose cardiac CT for coronary calcium scoring performed

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with a coronary artery calcium score (CACS) measured with a low-dose CT between 100 and 1000 and absence of significant ischemia (≥ 12 % of the myocardium) on myocardial perfusion scintigraphy.
Age ≥ 18 years
Affiliation to a social security regime
Signed informed consent.

Exclusion criteria

Exclusion Criteria :

Previous acute coronary syndrome or coronary revascularisation
LVEF < 40 %
Previous severe adverse reaction to iodinated contrast agent
Irregular heart rhythm (chronic atrial fibrillation, numerous extrasystoles)
Severe asthma
Chronic kidney disease (eGFR < 45 ml/min/1.73 m2)
Waldenstrom disease
Multiple myeloma
Autoimmune / inflammatory disease requiring immunosuppressive treatment.
Active cancer.
Confirmed or suspected pregnancy
Breast feeding
Impossibility to stay immobile and maintain the supine position during 30 minutes.
Patient deprived of liberty or under legal protection measure
Participation to an interventional trial involving the use of radiation during the two years of the study.
Participation to an interventional trial with the use of new drugs between the inclusion and one month after injecting 68Ga-DOTATATE.