Microdosing, Non-randomized, Clinical Trial to Investigate Binding of Positron Emission Tomography Tracer [68ga]Ga-DOTA-Cys-ATH001 Targeting Platelet-derived Growth Factor Receptor Beta (PDGFRß) in Healthy Subject as Compared to Patients With Cardiac Fibrosis.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- PET-tracer binding in myocardium
研究概览
简要总结
An observational, cross-sectional, longitudinal, microdosing Position Emission Tomography (PET) imaging study to investigate platelet derived growth factor receptor beta (PDGFRß) expression in the heart of patients with high or low risk of heart failure after a ST-Elevation Myocardial Infarction (STEMI) after a percutaneous coronary intervention (PCI) with a stent procedure, as well as in patients with heart failure with preserved ejection fraction (HFpEF) and healthy individuals.
详细描述
PDGFRß is a biomarker for pericytes which are identified as the progenitor of myofibroblast and fibroblast responsible for extra-cellular matrix proteins deposition in fibrotic heart. The Positron Emission Tomography (PET) tracer [68Ga]Ga-Dodecane tetra acetic acid (DOTA)-Cys-ATH001 is a marker for fibrogenic cells by targeting the surface receptor PDGFRß.
Four cohorts are examined by Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) or separate Positron Emission Tomography/Computed Tomography (PET/CT) and MRI using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to give written informed consent for participation in the trial and able to comply with all trial procedures and requirements.
- •Male or female participant aged 40 to 70 years, inclusive, at the screening visit.
- •Women of childbearing potential must practice abstinence from heterosexual intercourse or must agree to use a highly effective method of contraception.
- •Cohort-specific inclusion criteria:
- •Cohort 1, STEMI high-risk patients:
- •NT-proBNP >500 pg/mL within 48 hrs after PCI
- •Post-PCI Thrombolysis In Myocardial Infarction (TIMI) score <
- •No previous history of coronary artery disease or heart failure.
- •Cohort 2, STEMI low-risk patients
- •NT-proBNP <500 pg/mL within 48 hrs after PCI
- •Post-PCI TIMI score
- •No previous history of coronary artery disease or heart failure.
- •Cohort 3 (HFpEF patients)
- •Presence of signs and symptoms of HF
- •Ejection Fraction ≥50%
- •Elevated levels of natriuretic peptides (NT-proBNP≥125pg/mL)
- •At least one of the following:
- •Relevant structural heart disease (left ventricular hypertrophy or left atrial enlargement)
- •Diastolic dysfunction
- •Cohort 4 (healthy participants)
- •Individuals with no history of coronary disease or heart failure.
- •Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG, and laboratory values at the time of the screening visit, as judged by the Investigator.
排除标准
- •Any contraindication for MRI according to a standard checklist
- •Having worked as a metal worker or welder.
- •Contraindication for gadolinium-based contrast agents such as risk of nephrogenic systemic fibrosis (NSF) or allergy to gadolinium.
- •Kidney dysfunction measured as estimated Glomerular filtration rate (eGFR)<30 mL/min/1.73m2
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial or influence the results or the participant's ability to participate in the trial.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the screening visit.
- •Any malignancy within the past 12 months before the screening visit, with the exception of successfully treated basal cell carcinoma of the skin or in situ prostate cancer under active surveillance, with no interventions scheduled during the period of trial participation.
- •Any active gastrointestinal hemorrhage in the past six months.
- •Acute or chronic disabling stroke.
- •Aortic aneurysm or aortic dissection.
- •Hypertensive crisis.
- •Circulatory unstable condition in need for mechanical support.
- •Any planned major surgery within the duration of the trial participation.
- •Participants who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
- •Poor peripheral venous access, as judged by the Investigator.
- •The participant has any laboratory abnormality or condition that, in the Investigator's opinion, could adversely affect the safety of the participant or impair the assessment of trial results.
- •The participant is using any prohibited concomitant medications as described in the protocol, at the discretion of the Investigator.
- •The Investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.
- •Additional exclusion criteria for all participants (cohorts 1,2 and 4):
- •History of coronary artery disease or heart failure.
结局指标
主要结局
PET-tracer binding in myocardium
时间窗: At PET/MRI baseline, and at PET/MRI at 2-8 months after baseline (cohort 1 and 2)
Difference in \[68Ga\]Ga-DOTA-Cys-ATH001 Standardized Uptake Value (SUV)mean / SUVmax / SUVtot in the whole myocardium of healthy subjects compared with STEMI high-risk and low-risk patients, and HFpEF patients.
PET-tracer binding in the infarct
时间窗: At PET/MRI baseline, and at PET/MRI at 2-8 months after baseline (cohort 1 and 2)
Difference in uptake of \[68Ga\]Ga-DOTA-Cys-ATH001 in the infarct, as identified by Gd-MRI compared to uptake in healthy myocardium.
次要结局
未报告次要终点