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Positron Emission Tomography (PET) Imaging of Thrombosis

Primary Purpose

Atrial Fibrillation, COVID-19, Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
[64Cu]FBP8
PET/MR
Blood Collection
Electrocardiogram
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Atrial Fibrillation focused on measuring PET-MRI

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

For Atrial Fibrillation Patient subjects:

  • History of atrial fibrillation or paroxysmal atrial fibrillation;
  • Retrospective enrollment: TEE to evaluate LAA within the last 14 days, provided the anticoagulation regimen the patient is on is not changed after the TEE. If a patient has a negative TEE and continues the same stable anti-coagulation regimen he/she is on, then it is extremely unlikely that a new thrombus will develop in the left atrial appendage within the next two weeks. Likewise, if a patient not taking any anti-coagulation has a thrombus in the left atrial appendage, then it is extremely unlikely that this thrombus will resolve spontaneously in the next 14 days if the patient continues not to take any anticoagulation. If the TEE leads to a change being made in the anticoagulation regimen (started/stopped/dose modified), then a time window of 72 hours from the TEE to PET imaging will be used. This scheme will ensure that the TEE can serve as an accurate gold standard;
  • Prospective enrollment: TEE to evaluate LAA scheduled in upcoming 14 days;

For COVID-19 Patient subjects:

  • Positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper or lower respiratory tract analyzed by a certified lab with an FDA approved assay within the last month;
  • Patient not requiring mechanical ventilation;

For Cancer Patient subjects:

• Patient is diagnosed with cancer;

For Other Patient subjects:

  • Ultrasound- or CT-confirmed or high likelihood of thrombus (e.g., elevated D-dimer)
  • Has not received thrombolytics

Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • Subjects less than 18 years of age;
  • Electrical implants such as cardiac pacemaker or perfusion pump;
  • Pregnant or breastfeeding (a negative STAT quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
  • Claustrophobic reactions;
  • Subjects will be excluded if research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
  • Unable to lie comfortably on a bed inside the PET scanner;
  • Subjects under direct or indirect (i.e. same department as PIs) supervision of the principal investigator;
  • Body weight over the weight limit for the moving table (> 300 lbs for the MRI table and >441 lbs for the CT table);
  • Metallic or electric implants contraindicated for MR-PET scanning when applicable;
  • Does not have the ability to give written informed consent.
  • Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures);

Additional exclusion criteria for Atrial Fibrillation Patient subjects:

  • Stroke within the last 3 months;
  • Myocardial infarction within the last 3 months;
  • Cardiac or major surgery within the last 3 months;
  • History of chest pain within the last 6 weeks unless followed by a subsequent stress test or coronary angiography;
  • History of syncope within the last 6 weeks;
  • Heart rate persistently >120 bpm or persistently < 50 bpm;
  • Presence of daytime pauses > 3s

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Healthy Volunteers

Atrial Fibrillation Patients

COVID-19 Patients

Cancer Patients

Other Thrombotic Condition Patients

Arm Description

Twenty (20) healthy adult subjects will be injected with [64Cu]FBP8 to establish the safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden of the probe. All subjects will be imaged using PET/MR. Healthy subjects will undergo blood collection before, during, and after the scan. Healthy subjects will also undergo electrocardiogram before and after the scan. An interim review of the data will be conducted after the first six subjects receive the study agent and complete all safety assessments.

Thirty-five (35) patients with LAA thrombus documented by TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus with MR-PET. The TEE studies in these patients will be part of their routine clinical care. Thirty-five (35) patients with atrial fibrillation and negative TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus. Forty (40) patients with atrial fibrillation who are scheduled for TEE in the upcoming 14 days will be injected with [64Cu]FBP8 and imaged for LAA thrombus.

Thirty (30) COVID-19 patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.

Thirty (30) cancer patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.

Fifty (50) patients with other thrombotic conditions will be injected with [64Cu]FBP8 and imaged for thrombi in the body.

Outcomes

Primary Outcome Measures

Complete blood count
To model pharmacokinetics of [64Cu]FBP8 metabolism in healthy volunteers.
Target to Background Ratio LAA
To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in patients with atrial fibrillation.
Target to Background Ratio
To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect thrombosis in patients with known thrombus or suspicion of thrombus.
Time activity curve
To evaluate human dosimetry and radiation burden in healthy volunteers.

Secondary Outcome Measures

Full Information

First Posted
January 28, 2019
Last Updated
December 20, 2022
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03830320
Brief Title
Positron Emission Tomography (PET) Imaging of Thrombosis
Official Title
Preliminary Evaluation of [64Cu]FBP8 in Healthy Individuals and Subjects With Known or at Risk of Developing Thrombosis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2016 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
January 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate a new radiotracer called 64Cu-FBP8 for PET-MR imaging of thrombosis. The tracer has the potential of detecting thrombosis anywhere in the body, for instance in the left atrial appendage of patients with atrial fibrillation, and thereby may provide a non-invasive alternative to the current standard-of-care methods.
Detailed Description
The primary objectives of this study are: To evaluate the safety of [64Cu]FBP8 and its whole body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers. To establish the accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in patients with atrial fibrillation. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with COVID-19. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with cancer. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with known or suspicion of thrombus outside of the left atrial appendage.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, COVID-19, Cancer, Thrombosis
Keywords
PET-MRI

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Healthy Volunteers
Arm Type
Active Comparator
Arm Description
Twenty (20) healthy adult subjects will be injected with [64Cu]FBP8 to establish the safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden of the probe. All subjects will be imaged using PET/MR. Healthy subjects will undergo blood collection before, during, and after the scan. Healthy subjects will also undergo electrocardiogram before and after the scan. An interim review of the data will be conducted after the first six subjects receive the study agent and complete all safety assessments.
Arm Title
Atrial Fibrillation Patients
Arm Type
Experimental
Arm Description
Thirty-five (35) patients with LAA thrombus documented by TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus with MR-PET. The TEE studies in these patients will be part of their routine clinical care. Thirty-five (35) patients with atrial fibrillation and negative TEE will be injected with [64Cu]FBP8 and imaged for LAA thrombus. Forty (40) patients with atrial fibrillation who are scheduled for TEE in the upcoming 14 days will be injected with [64Cu]FBP8 and imaged for LAA thrombus.
Arm Title
COVID-19 Patients
Arm Type
Experimental
Arm Description
Thirty (30) COVID-19 patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.
Arm Title
Cancer Patients
Arm Type
Experimental
Arm Description
Thirty (30) cancer patients will be injected with [64Cu]FBP8 and imaged for thrombi in the body.
Arm Title
Other Thrombotic Condition Patients
Arm Type
Experimental
Arm Description
Fifty (50) patients with other thrombotic conditions will be injected with [64Cu]FBP8 and imaged for thrombi in the body.
Intervention Type
Drug
Intervention Name(s)
[64Cu]FBP8
Other Intervention Name(s)
64Cu-FBP8
Intervention Description
Injection of Copper-64 radiopeptide to detect thrombosis
Intervention Type
Device
Intervention Name(s)
PET/MR
Other Intervention Name(s)
PET-MR
Intervention Description
Whole body imaging using Siemens mMR PET/MR scanner
Intervention Type
Procedure
Intervention Name(s)
Blood Collection
Intervention Description
A total of 9 cc of blood sampled before, during, and after imaging for clinical chemistry
Intervention Type
Procedure
Intervention Name(s)
Electrocardiogram
Other Intervention Name(s)
ECG
Intervention Description
A standard 12-lead ECG will be obtained pre-and-post injection with radiotracer
Primary Outcome Measure Information:
Title
Complete blood count
Description
To model pharmacokinetics of [64Cu]FBP8 metabolism in healthy volunteers.
Time Frame
36 hours
Title
Target to Background Ratio LAA
Description
To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in patients with atrial fibrillation.
Time Frame
4 hours
Title
Target to Background Ratio
Description
To determine the signal threshold of [64Cu]FBP8 that produces the highest accuracy of [64Cu]FBP8 -PET to detect thrombosis in patients with known thrombus or suspicion of thrombus.
Time Frame
4 hours
Title
Time activity curve
Description
To evaluate human dosimetry and radiation burden in healthy volunteers.
Time Frame
48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
For Atrial Fibrillation Patient subjects: History of atrial fibrillation or paroxysmal atrial fibrillation; Retrospective enrollment: TEE to evaluate LAA within the last 14 days, provided the anticoagulation regimen the patient is on is not changed after the TEE. If a patient has a negative TEE and continues the same stable anti-coagulation regimen he/she is on, then it is extremely unlikely that a new thrombus will develop in the left atrial appendage within the next two weeks. Likewise, if a patient not taking any anti-coagulation has a thrombus in the left atrial appendage, then it is extremely unlikely that this thrombus will resolve spontaneously in the next 14 days if the patient continues not to take any anticoagulation. If the TEE leads to a change being made in the anticoagulation regimen (started/stopped/dose modified), then a time window of 72 hours from the TEE to PET imaging will be used. This scheme will ensure that the TEE can serve as an accurate gold standard; Prospective enrollment: TEE to evaluate LAA scheduled in upcoming 14 days; For COVID-19 Patient subjects: Positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper or lower respiratory tract analyzed by a certified lab with an FDA approved assay within the last month; Patient not requiring mechanical ventilation; For Cancer Patient subjects: • Patient is diagnosed with cancer; For Other Patient subjects: Ultrasound- or CT-confirmed or high likelihood of thrombus (e.g., elevated D-dimer) Has not received thrombolytics Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: Subjects less than 18 years of age; Electrical implants such as cardiac pacemaker or perfusion pump; Pregnant or breastfeeding (a negative STAT quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate); Claustrophobic reactions; Subjects will be excluded if research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months); Unable to lie comfortably on a bed inside the PET scanner; Subjects under direct or indirect (i.e. same department as PIs) supervision of the principal investigator; Body weight over the weight limit for the moving table (> 300 lbs for the MRI table and >441 lbs for the CT table); Metallic or electric implants contraindicated for MR-PET scanning when applicable; Does not have the ability to give written informed consent. Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures); Additional exclusion criteria for Atrial Fibrillation Patient subjects: Stroke within the last 3 months; Myocardial infarction within the last 3 months; Cardiac or major surgery within the last 3 months; History of chest pain within the last 6 weeks unless followed by a subsequent stress test or coronary angiography; History of syncope within the last 6 weeks; Heart rate persistently >120 bpm or persistently < 50 bpm; Presence of daytime pauses > 3s
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David E Sosnovik, MD
Phone
617-724-3407
Email
sosnovik@nmr.mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Anne L Philip, MPH
Phone
617-726-0431
Email
alphilip@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ciprian Catana, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David E Sosnovik, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
34656469
Citation
Izquierdo-Garcia D, Desogere P, Philip AL, Mekkaoui C, Weiner RB, Catalano OA, Iris Chen YC, DeFaria Yeh D, Mansour M, Catana C, Caravan P, Sosnovik DE. Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance. JACC Cardiovasc Imaging. 2022 Mar;15(3):504-515. doi: 10.1016/j.jcmg.2021.08.009. Epub 2021 Oct 13.
Results Reference
derived

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Positron Emission Tomography (PET) Imaging of Thrombosis

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