Platelet Derived Growth Factor Receptor ß (PDGFRß) Imaging in Cardiac Fibrosis

NCT06956560 | Recruiting

• 1 other identifier: PARIS
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ST-Elevation Myocardial Infarction (STEMI); Heart Failure With Preserved Ejection Fraction (HFpEF)

Outcome Measures

Primary Outcomes (2)

• PET-tracer binding in myocardium

  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.

  At PET/MRI baseline, and at PET/MRI at 2-8 months after baseline (cohort 1 and 2)

• PET-tracer binding in the infarct

  Difference in uptake of \[68Ga\]Ga-DOTA-Cys-ATH001 in the infarct, as identified by Gd-MRI compared to uptake in healthy myocardium.

  At PET/MRI baseline, and at PET/MRI at 2-8 months after baseline (cohort 1 and 2)

Study Arms (4)

Individuals with high risk of heart failure after STEMI

Individuals with high risk of heart failure after STEMI are examined by PET 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) at one week after PCI/stent intervention and at 2-8 months after PCI/stent.

Radiation: PET/MRI or separate PET/CT and MRI

Individuals with low risk of heart failure after STEMI

Individuals with low risk of heart failure after STEMI are examined by PET 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) at one week after PCI/stent intervention and at 2-8 months after PCI/stent.

Radiation: PET/MRI or separate PET/CT and MRI

Individuals diagnosed with HFpEF and with signs/symptoms of heart failure

Individuals diagnosed with HFpEF are examined by PET 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) once after inclusion.

Radiation: PET/MRI or separate PET/CT and MRI

Healthy control individuals

Healthy control individuals are examined by PET 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) once after inclusion.

Radiation: PET/MRI or separate PET/CT and MRI

Interventions

PET/MRI or separate PET/CT and MRI RADIATION

PET/MRI or separate 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). Cohort 1 and 2 are examined twice, first one week after PCI/stent and then a second examination 2 to 8 months after the first. Cohorts 3, and 4 are examined once.

Healthy control individuals; Individuals diagnosed with HFpEF and with signs/symptoms of heart failure; Individuals with high risk of heart failure after STEMI; Individuals with low risk of heart failure after STEMI

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Eligible patients with STEMI high- and low-risk, and HFpEF will be recruited and/or identified from referral sites, by Uppsala University Hospital.

You may qualify if:

• 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 1, STEMI high-risk patients:
• NT-proBNP \>500 pg/mL within 48 hrs after PCI
• Post-PCI Thrombolysis In Myocardial Infarction (TIMI) score \<3.
• 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 3.
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (1)

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood samples for the future determination of exploratory biomarkers prior to administration of the PET-tracer will be collected at screening and at each PET examination. Biomarkers to be analyzed will include, but are not limited to: Nt-proBNP, Collagen I and III, C-terminal propeptide of procollagen type I (PICP), procollagen type I N-terminal propeptide (PINP), ProC3, procollagen type III amino-terminal propeptide (PIIINP), matrix metalloproteinases (MMPs)(e.g. MMP-1, MMP-2, MMP7…), tissue inhibitors of metalloproteinase (TIMPs) (e.g. TIMP1, TIMP-4…), transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), galectin-3 (Gal-3), pro-inflammatory mediators (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-4, and IL-6…), microRNA (miR-1, miR-21…).

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Karl-Henrik Grinnemo, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karl-Henrik Grinnemo, MD, PhD

CONTACT

+46186110000; karl-henrik.grinnemo@uu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: May 4, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)