Macrophage PET/CT Imaging Using 64Cu-DOTATATE for the Diagnosis of Cardiac Sarcoidosis (CuDOSIS)

Macrophage PET/CT Imaging for the Diagnosis of Cardiac Sarcoidosis

The purpose of the CuDOSIS study is to examine the diagnostic value of activated macrophage imaging in patients with or under evaluation for cardiac sarcoidosis. The PET/CT tracer 64Cu-DOTATATE is used as a tool to identify activated macrophages. The trial is an open-label prospective study. The study will include 54 participants from the Department of Cardiology and the Department of Clinical Physiology, Nuclear Medicine, and PET at Rigshospitalet. Further, the study will include data from 22 patients with NET who have been scanned with 64Cu-DOTATATE PET/CT previously as negative controls.

Participants will be included in the following groups:

Group A: 22 patients with clinically suspected cardiac sarcoidosis Group B: 22 patients with known cardiac sarcoidosis Group C: Up to 10 patients with clinically suspected or confirmed acute lymphocytic myocarditis Group D: 22 patients with NET without known inflammatory heart disease who have previously been scanned with 64Cu-DOTATATE PET/CT as part of their routine diagnostic work-up or follow-up (control group)

Study Overview

• Status: Recruiting
• Conditions: Cardiac Sarcoidosis
• Intervention / Treatment: Diagnostic test: 64Cu-DOTATATE PET/CT scan

Detailed Description

Cardiac involvement is considered a serious condition and a frequent cause of death in patients with sarcoidosis. 18F-FDG PET/CT is currently used as part of the diagnostic criteria for cardiac sarcoidosis, but it has shown limitations in the evaluation of cardiac sarcoidosis due to the high physiological uptake of FDG in normal cardiac muscle. Elaborate preparations are required for patients including either a low-carbohydrate diet followed by long fasting or heparin loading before FDG-PET. In heparin loading, the rare adverse effect of heparin-induced thrombocytopenia should be considered. Therefore, it is of interest to find a PET/CT tracer that displays high sensitivity and specificity without requiring thorough patient preparation and minimizing any adverse effects.

A potential tracer is the somatostatin-based tracer 64Cu-DOTATATE, which is routinely used for the diagnosis and monitoring of treatment response in patients with neuroendocrine tumors. Inflammatory cells, including macrophages that are found in sarcoid granulomas, express somatostatin receptors on their surface, whereas normal cardiomyocytes do not. This allows for the potential use of macrophage imaging in cardiac sarcoidosis.

In the CuDOSIS trial, groups A and B (suspected and confirmed cardiac sarcoidosis, respectively) will be scanned with 64Cu-DOTATATE PET/CT in addition to the routinely performed 18F-FDG PET/CT. Further, to examine whether the macrophage infiltration pattern is different in patients with cardiac sarcoidosis and other inflammatory heart diseases, a group of patients with confirmed or clinically suspected myocarditis will be included (group C); this group will only be scanned with 64Cu-DOTATATE PET/CT. Finally, data from a group of patients with neuroendocrine tumours (negative controls) who have previously been scanned with 64Cu-DOTATATE will be included.

• Study Type: Observational
• Enrollment (Estimated): 76

Contacts and Locations

• Study Contact: Name: Finn Gustafsson, MD,PhD,DMSc; Phone Number: +45 35456340; Email: finn.gustafsson@regionh.dk
• Study Contact Backup: Name: Adelina Yafasova, MD; Phone Number: +45 35456252; Email: adelina.henney.yafasova@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
    • Contact: Finn Gustafsson, MD,PhD,DMSc; Phone Number: +45 35456340; Email: finn.gustafsson@regionh.dk
    • Contact: Adelina Yafasova, MD; Phone Number: +45 35456252; Email: adelina.henney.yafasova@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study will include adults (18 years or older) from the Department of Cardiology and Department of Clinical Physiology, Nuclear Medicine, and PET at Rigshospitalet. The study will include a total of 76 participants: 54 patients from groups A-C and data from 22 patients from group D.

Description

Inclusion Criteria:

• Age => 18 years
• Group A: 22 patients with clinically suspected cardiac sarcoidosis Group B: 22 patients with known cardiac sarcoidosis Group C: Up to 10 patients with clinically suspected or confirmed acute lymphocytic myocarditis Group D: 22 patients with NET without known inflammatory heart disease who have previously been scanned with 64Cu-DOTATATE PET/CT as part of their routine diagnostic work-up or follow-up (control group)

Exclusion Criteria:

• Severe obesity (weight > 140 kg)
• Pregnancy (negative point-of-care urine/serum human chorion gonadotropin is required in all fertile women)
• Severe claustrophobia
• Known allergy to 64Cu-DOTATATE
• Clinically critical condition which makes PET/CT impossible
• Diabetes with insulin dependence

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; 22 patients with clinically suspected cardiac sarcoidosis	Diagnostic test: 64Cu-DOTATATE PET/CT scan; Patients in group A-C will have a 64Cu-DOTATATE PET/CT scan performed in addition to routine clinical procedures. Group D has had 64Cu-DOTATATE PET/CT performed as part of their clinical diagnostic work-up or follow-up; these data are retrospectively identified and included in the study, and group D will not be subject to any scans in the study.
Group B; 22 patients with known cardiac sarcoidosis	Diagnostic test: 64Cu-DOTATATE PET/CT scan; Patients in group A-C will have a 64Cu-DOTATATE PET/CT scan performed in addition to routine clinical procedures. Group D has had 64Cu-DOTATATE PET/CT performed as part of their clinical diagnostic work-up or follow-up; these data are retrospectively identified and included in the study, and group D will not be subject to any scans in the study.
Group C; Up to 10 patients with clinically suspected or confirmed acute lymphocytic myocarditis	Diagnostic test: 64Cu-DOTATATE PET/CT scan; Patients in group A-C will have a 64Cu-DOTATATE PET/CT scan performed in addition to routine clinical procedures. Group D has had 64Cu-DOTATATE PET/CT performed as part of their clinical diagnostic work-up or follow-up; these data are retrospectively identified and included in the study, and group D will not be subject to any scans in the study.
Group D; 22 patients with NET without known inflammatory heart disease who have previously been scanned with 64Cu-DOTATATE PET/CT as part of their routine diagnostic work-up or follow-up (control group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tracer uptake - cardiac sarcoidosis and neuroendocrine tumor (negative control)	The proportion of patients with tracer uptake in the heart on 64Cu-DOTATATE PET/CT in patients with verified cardiac sarcoidosis and the proportion of patients without tracer uptake in the heart on 64Cu-DOTATATE PET/CT for patients with a neuroendocrine tumor without a history of inflammatory heart disease (the control group).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-month rates of adverse outcomes	Death, heart failure hospitalizations, decrease of left ventricular ejection fraction to <10% and <50%, new-onset ventricular tachycardia, new-onset atrioventricular block, implantable cardioverter-defibrillator implantation, shocks from implantable cardioverter-defibrillator, pacemaker implantation, cardiac resyncronization therapy	2 years
Tracer uptake - myocarditis	The proportion of patients with tracer uptake in the heart on 64Cu-DOTATATE PET/CT in patients with verified acute lymphocytic myocarditis	2 years
Distribution of tracer uptake	The distribution of tracer uptake in the heart in patients with cardiac sarcoidosis and acute lymphocytic myocarditis, respectively	2 years

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Finn Gustafsson, MD,PhD,DMSc, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 14, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hypersensitivity; Hypersensitivity, Delayed; Sarcoidosis
• Other Study ID Numbers: H-23035676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The overall results of the trial will be made available. Individual participant data (IPD) will not be made available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No