Clinical trial NCT03505346: 68 Ga-NODAGA-E[c(RGDγK)]2: Positron Emission Tomography Tracer for Imaging of Angiogenesis in Ischemic Heart Disease
Official title: 68 Ga-NODAGA-E[c(RGDγK)]2: Positron Emission Tomography Tracer for Imaging of Angiogenesis in Ischemic Heart Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Ischemic Heart Disease
Keywords: Positron Emission Tomography
nuclear medicine
prognosis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2018-04-23
Enrollment: 42
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim is to examine the expression of αvβ3 integrin using a novel selective radiotracer in patients with chronich ischemic heart disease and investigate if it is a suitable tool for predicting myocardial recovery and thus prognosis after intervention.

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. Ischemic heart disease is most commently caused by arteriosclerosis of the coronary artery.

If chronic ischemic heart disease is left untreated, it will lead to symptoms to the patient. These symptons occur when the myocardiel oxygen demand exceeds the oxygen provided, due to coronary occlusion.

If the heart suffers from ischemia, 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.

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 before interventions may correlate to recovery of cardiac function and thus serve as a prognostic marker after intervention.

Eligibility criteria: Inclusion Criteria:

* Age over 50 years
* Patient with known chornic ischemic Heart disease admitted to Rigshospitalet to either PCI og CABG

Exclusion Criteria:

* 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)
* Conversion from PCI to CABG
* 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¨
* Type I or II diabetes

Primary outcomes:
measure: To evaluate myocardial angiogenesis
timeFrame: 30-35 days
Secondary outcomes:
measure: Correlation between 68Ga-NODAGA-E[c(RGDyK)]2 and myocardial perfusion
timeFrame: 30-35 days
measure: Correlation between 68Ga-NODAGA-E[c(RGDyK)]2 and functional recovery
timeFrame: 30-35 days
measure: Correlatino between 68Ga-NODAGA-E[c(RGDyK)]2 and viability
timeFrame: 30-35 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Physiology, Nuclear Medicine and PET
state: Region Hovedstaden
Study officials:
affiliation: Rigshospitalet, Denmark
name: Andreas Kjær, MD
role: STUDY_DIRECTOR
References: