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18F-Flutemetamol and Plaque Vulnerability

Primary Purpose

Atherosclerosis

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
18F-Flutemetamol PET/MRI
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Atherosclerosis focused on measuring PET/MRI, Amyloid, Flutemetamol

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  • All patients:

    • Age18years and older (no maximum age)
    • Informed consent by signed informed consent form regarding this study
  • Patients, who are scheduled for carotid endarterectomy:

    o Inclusion criteria for carotid endarterectomy:

    • Symptomatic stenosis (TIA or CVA) within last 14days and high grade stenosis (70-99%)
    • In men, carotid artery stenosis between 50-69% is considered significant when related to clinical symptoms
  • Patients, who are not scheduled for carotid endarterectomy:

    • Patients who have experienced a TIA/CVA/amaurosis fugax (a 'TIA of the eye') within the last 14 days and abnormal findings on imaging of the carotids:

      • Women with an ipsilateral carotid artery stenosis between 30-69% based on duplex ultrasonography, CTA, or MRA
      • Men with an ipsilateral carotid artery stenosis between 30-49% based on duplex ultrasonography, CTA, or MRA
      • Patients meeting inclusion criteria for carotid endarterectomy, but with contra- indications for CEA

Exclusion Criteria:

  • All patients:

    • Severe cognitive impairment, neurological deficit or comorbidity causing the study to be too high a burden for the patient or disrupting patient's co- operation with scan procedures
    • Evident other causality for stroke (cardiac embolus, small vessel disease or thrombogenic diathesis)
    • Pregnant women and nursing mothers
    • Contra-indications for MRI (49):

      • Ferromagnetic implants, such as pacemakers and other electronic implants
      • Ferromagnetic (intracerebral) vascular clips
      • Metallic cochlear implants
      • Metallic splinters in eye(s) or other magnetic metallic foreign bodies elsewhere
      • Claustrophobia
    • Relative contra-indications for MRI-contrast agents (50):

      • GFR <30ml/min/1,73m2
      • Previous allergic reaction to MRI contrast agent
    • Contra-indication 18F-Flutemetamol:

      • Known allergic reaction to flutemetamol or polysorbate 80 or any of the excipients.
      • Severe liver dysfunction.
  • Patients undergoing CEA:

    • Comorbidity associated with high operative risk
    • Occlusion of the internal carotid artery on the symptomatic side
    • Near occlusion on the symptomatic side
    • Complete infarction of the symptomatic anterior circulation/severe neurological deficit

Sites / Locations

  • Maastricht University Medical Centre (MUMC+)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

18F-Flutemetamol PET/MRI dynamic

18F-Flutemetamol PET/MRI CEA

18F-Flutemetamol PET/MRI

Arm Description

All included patients will be patients with a recent stroke and a significant carotid plaque. The first 5 patients will undergo a slightly longer scan protocol to determine optimal scan time for the use of 18F-Flutemetamol in atherosclerosis imaging.

10 patients will be selected from patients that will undergo carotid endarterectomy (CEA) and will undergo the the optimized (shorter) scan protocol with 18F-Flutemetamol. The decision for this operation is made by the surgeon and neurologist and based on clinical standards and is thus independent of study participation.

The remaining 10 patients will undergo the optimized (shorter) scan protocol with 18F-Flutemetamol.

Outcomes

Primary Outcome Measures

18F-Flutemetamol uptake carotids
measured as SUV and TBR

Secondary Outcome Measures

18F-Flutemetamol uptake coronaries
measured as SUV and TBR
18F-Flutemetamol uptake in the brain
measured as SUVR
CEA - plaque inflammation
macrophage content
MRI plaque characteristics carotid
semi quantitive analysis
CEA - plaque amyloid burden
Immunohistochemistry

Full Information

First Posted
September 19, 2017
Last Updated
July 10, 2019
Sponsor
Maastricht University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03291093
Brief Title
18F-Flutemetamol and Plaque Vulnerability
Official Title
Identification of Plaque Vulnerability Wit PET/MRI: a Feasibility Study of 18F-Flutemetamol in Atherosclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2018 (Actual)
Primary Completion Date
December 31, 2019 (Anticipated)
Study Completion Date
December 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
Rationale: Amyloid beta (Ab) is mainly known for its role in Alzheimer's disease (AD) pathology. However, Ab seems not only to be involved in AD pathology, but also in atherosclerosis, which might explain the remarkable similarities in risk factors between these two pathologies. In vitro studies suggest that a major part of this association is based on the ability of amyloid to lead to macrophage activation and thus inflammation. These data lead to the hypothesis that Ab is associated with plaque vulnerability. 18F-Flutemetamol is a PET tracer with high affinity for Ab. This has been extensively studied in AD patients. Objective: To validate 18F-Flutemetamol PET in the evaluation of plaque vulnerability. Study design: A cross-sectional validation study. Study population: 25 adults, who have recently (<14days) experienced a transient ischemic attack (TIA) or stroke with a carotid artery plaque of ≥30% and without evidence of another etiology than carotid atherosclerosis (i.e. cardiac or small vessel). Of these 25 patients, 10 patients will be included who have been scheduled for carotid endarterectomy (CEA). The other 15 will be selected of patients who are not scheduled to undergo CEA. Intervention: All patients will undergo a PET/MRI scan with 18F-Flutemetamol, either before the scheduled CEA or within the first 30 days following the cerebrovascular event. Imaging will include the carotid and coronary arteries as well as the brain. Main study parameters/endpoints: Tracer uptake in the carotid artery will be correlated to vulnerable plaque characteristics as assessed by MRI. In the 10 CEA patients, tracer uptake and MR imaging of different plaque characteristics will be validated with plaque histology of the surgically removed specimen. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no additional benefit for study subjects. Study subjects will receive the same treatment as non-participating patients. Patients will be screened for in- and exclusion criteria to minimize risks. For optimal MR imaging patients will be injected with a Gadolinium based contrast agent, which is a common procedure and associated with very low risk of complications. The PET tracer 18F-flutemetamol has been studied extensively and is currently used in patients with AD. Adverse events were not frequent and mainly mild. The radioactivity dose will be around 6.8 mSv.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerosis
Keywords
PET/MRI, Amyloid, Flutemetamol

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
18F-Flutemetamol PET/MRI dynamic
Arm Type
Experimental
Arm Description
All included patients will be patients with a recent stroke and a significant carotid plaque. The first 5 patients will undergo a slightly longer scan protocol to determine optimal scan time for the use of 18F-Flutemetamol in atherosclerosis imaging.
Arm Title
18F-Flutemetamol PET/MRI CEA
Arm Type
Experimental
Arm Description
10 patients will be selected from patients that will undergo carotid endarterectomy (CEA) and will undergo the the optimized (shorter) scan protocol with 18F-Flutemetamol. The decision for this operation is made by the surgeon and neurologist and based on clinical standards and is thus independent of study participation.
Arm Title
18F-Flutemetamol PET/MRI
Arm Type
Experimental
Arm Description
The remaining 10 patients will undergo the optimized (shorter) scan protocol with 18F-Flutemetamol.
Intervention Type
Drug
Intervention Name(s)
18F-Flutemetamol PET/MRI
Intervention Description
All patients will undergo a PET/MRI of the carotids after 18F-Flutemetamol injection.
Primary Outcome Measure Information:
Title
18F-Flutemetamol uptake carotids
Description
measured as SUV and TBR
Time Frame
0-120min
Secondary Outcome Measure Information:
Title
18F-Flutemetamol uptake coronaries
Description
measured as SUV and TBR
Time Frame
0-150min
Title
18F-Flutemetamol uptake in the brain
Description
measured as SUVR
Time Frame
0-150min
Title
CEA - plaque inflammation
Description
macrophage content
Time Frame
1-14 dys
Title
MRI plaque characteristics carotid
Description
semi quantitive analysis
Time Frame
0-150min
Title
CEA - plaque amyloid burden
Description
Immunohistochemistry
Time Frame
1-14 dys

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria: All patients: Age18years and older (no maximum age) Informed consent by signed informed consent form regarding this study Patients, who are scheduled for carotid endarterectomy: o Inclusion criteria for carotid endarterectomy: Symptomatic stenosis (TIA or CVA) within last 14days and high grade stenosis (70-99%) In men, carotid artery stenosis between 50-69% is considered significant when related to clinical symptoms Patients, who are not scheduled for carotid endarterectomy: Patients who have experienced a TIA/CVA/amaurosis fugax (a 'TIA of the eye') within the last 14 days and abnormal findings on imaging of the carotids: Women with an ipsilateral carotid artery stenosis between 30-69% based on duplex ultrasonography, CTA, or MRA Men with an ipsilateral carotid artery stenosis between 30-49% based on duplex ultrasonography, CTA, or MRA Patients meeting inclusion criteria for carotid endarterectomy, but with contra- indications for CEA Exclusion Criteria: All patients: Severe cognitive impairment, neurological deficit or comorbidity causing the study to be too high a burden for the patient or disrupting patient's co- operation with scan procedures Evident other causality for stroke (cardiac embolus, small vessel disease or thrombogenic diathesis) Pregnant women and nursing mothers Contra-indications for MRI (49): Ferromagnetic implants, such as pacemakers and other electronic implants Ferromagnetic (intracerebral) vascular clips Metallic cochlear implants Metallic splinters in eye(s) or other magnetic metallic foreign bodies elsewhere Claustrophobia Relative contra-indications for MRI-contrast agents (50): GFR <30ml/min/1,73m2 Previous allergic reaction to MRI contrast agent Contra-indication 18F-Flutemetamol: Known allergic reaction to flutemetamol or polysorbate 80 or any of the excipients. Severe liver dysfunction. Patients undergoing CEA: Comorbidity associated with high operative risk Occlusion of the internal carotid artery on the symptomatic side Near occlusion on the symptomatic side Complete infarction of the symptomatic anterior circulation/severe neurological deficit
Facility Information:
Facility Name
Maastricht University Medical Centre (MUMC+)
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6229 HX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ellen Boswijk, MD
Phone
+31433876549
Email
ellen.boswijk@mumc.nl

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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18F-Flutemetamol and Plaque Vulnerability

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