Clinical trial NCT04043377: 68Ga-DOTATATE PET-CTA Imaging for the Early Detection of Progressing Coronary Atherosclerosis
Official title: 68Ga-DOTATATE PET-CTA Imaging for the Early Detection of Progressing Coronary Atherosclerosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronary Arteriosclerosis
Keywords: Coronary atherosclerosis
68Ga-DOTATATE
PET-CTA imaging
No significant myocardial ischemia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-08-02
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Absolute increase in calcium artery calcium scoring (CACS) per year.
timeFrame: 2 years
Secondary outcomes:
measure: Combined end point including cardiovascular death, acute coronary syndrome and ischemia-driven coronary revascularization.
timeFrame: 2 years
measure: Characterization of coronary plaques 1
timeFrame: 2 years
measure: Characterization of coronary plaques 2
timeFrame: 2 years
measure: Characterization of coronary plaques 3
timeFrame: 2 years
measure: Characterization of coronary plaques 4
timeFrame: 2 years
measure: Characterization of coronary plaques 5
timeFrame: 2 years
measure: MDS TBR of coronary arteries and global TBR of the thoracic aorta.
timeFrame: 2 years
measure: 68Ga-DOTATATE uptake in the parodontal bone.
timeFrame: 2 years
Other outcomes:
Locations:
city: Paris
country: France
facility: service de médecine nucléaire-Hôpital Bichat
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Fabien HYAFIL, Doctor
role: PRINCIPAL_INVESTIGATOR
References: