68 Ga-NODAGA-E[c(RGDγK)]2: Positron Emission Tomography Tracer for Imaging of Myocardial Angiogenesis

NCT ID: NCT03445884

Last Updated: 2020-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-20
• Study Completion Date: 2020-07-01

Brief Summary

The aim is to examine the expression of αvβ3 integrin using a novel selective radiotracer in patients with myocardial infarction and investigate if it is a suitable tool for predicting myocardial recovery and thus prognosis.

Detailed Description

Ischemic heart disease is worldwide the single most frequent cause of death. The number of patients surviving acute myocardial injury is increasing due to improved acute treatment. However, after the initial repair, the tissue undergoes a remodeling phase to compensate for the damaged area. This re-modeling phase can change the structure end geometry of the heart resulting in lower ejection fraction, leading to cardiac dysfunction, which eventually leads to heart failure. Understanding and ideally modifying the reparative mechanisms following myocardial infarction is increasingly important and may lead to improved outcome.

If the heart suffers from ischemia following an acute coronary event, the tissue reacts strongly to the hypoxia. The body will as a compensatory mechanism create new vessel to provide the tissue with oxygen. This is known as the biological process of angiogenesis. This complex process involves different angiogenic and pro-fibrotic transcription factors that initiate the restoration of capillaries by sprouting from the existing endothelial cells in response to hypoxia.

Time seem essential to protect and save the myocardium. An early onset of cytokines and growth factors is associated with a decline in cardiomyocytes apoptosis, smaller infarct areas, and decreased ventricular dilation. Therefore, an early induction of angiogenesis seems important for a good prognosis of the patient.

Integrin αvβ3 is a transmembrane cell surface receptor that is markedly upregulated in states of angiogenesis. It facilitates migration and proliferation and thereby allowing cells to respond to extracellular environment. Integrin αvβ3 is thus a key player in the angiogenic process. The integrin αvβ3 has a binding site for an RGD peptide (Arg-Gly-Asp motif) and this can be targeted by PET tracers.

RGD-based PET tracers have been shown to accumulate at the site of myocardial necrosis in both human and animal studies. The uptake seems to peak a few weeks after the infarction and may correlate to recovery of cardiac function and thus serve as a prognostic marker.

Conditions

Acute Myocardial Infarction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Acute myocardial infarctions group

200 MBq 68Ga-NODAGA-E\[c(RGDyK)\]2 administered IV. three times. 1-3 days after intervention, 7-10 days after intervention and 30-35 days after intervention.

Group Type: EXPERIMENTAL

68Ga-NODAGA-E[c(RGDyK)]2

Intervention Type: DRUG

200 MBq 68Ga-NODAGA-E\[c(RGDyK)\]2 administered IV.

Control group

200 MBq 68Ga-NODAGA-E\[c(RGDyK)\]2 administered IV. one time.

Group Type: ACTIVE_COMPARATOR

68Ga-NODAGA-E[c(RGDyK)]2

Intervention Type: DRUG

200 MBq 68Ga-NODAGA-E\[c(RGDyK)\]2 administered IV.

Interventions

68Ga-NODAGA-E[c(RGDyK)]2

200 MBq 68Ga-NODAGA-E\[c(RGDyK)\]2 administered IV.

Intervention Type: DRUG

Other Intervention Names

RGD-PET

Eligibility Criteria

Inclusion Criteria

• Age over 50 years

Acute myocardial infarction Group:

• Verified first-time acute myocardial infarction treated with PCI

Control Group:

• Previous healthy
• No known cardiac disease

Exclusion Criteria

• No prior history of acute coronary infarction
• No prior history of Heart surgery
• Not treated with anti-angiogenic medicine
• Subject with pacemaker, cochlear implant or insulin pump
• Pregnancy
• Lactation
• Severe claustrophobia
• Severe obesity (weight above 140kg)
• If a subject is in the fertile age, a pregnancy test will be use prior to injection to the PET_tracer
• If a subject is having a severe allergic reaction to the PET-tracer, the person will be excluded for the rest of the trial
• If the PET-tracer is administered subcutaneous, the person will be excluded for the rest of the trial¨
• Tupe I or II diabetes

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Simon Bentsen

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andreas Kjær, MD

Role: STUDY_DIRECTOR

Rigshospitalet, Denmark

Locations

Department of Physiology, Nuclear Medicine and PET

Copenhagen, Capital Region, Denmark

Countries

Denmark

Other Identifiers

EUDRACR-number: 2017-002709-36

Identifier Type: -

Identifier Source: org_study_id