NCT03291093

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
25

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2018

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 19, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 25, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

February 1, 2018

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2019

Completed
Last Updated

July 11, 2019

Status Verified

January 1, 2019

Enrollment Period

1.9 years

First QC Date

September 19, 2017

Last Update Submit

July 10, 2019

Conditions

Atherosclerosis

Keywords

PET/MRIAmyloidFlutemetamol

Outcome Measures

Primary Outcomes (1)

  • 18F-Flutemetamol uptake carotids

    measured as SUV and TBR

    0-120min

Secondary Outcomes (5)

  • 18F-Flutemetamol uptake coronaries

    0-150min

  • 18F-Flutemetamol uptake in the brain

    0-150min

  • CEA - plaque inflammation

    1-14 dys

  • MRI plaque characteristics carotid

    0-150min

  • CEA - plaque amyloid burden

    1-14 dys

Study Arms (3)

18F-Flutemetamol PET/MRI dynamic

EXPERIMENTAL

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.

Drug: 18F-Flutemetamol PET/MRI

18F-Flutemetamol PET/MRI CEA

EXPERIMENTAL

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.

Drug: 18F-Flutemetamol PET/MRI

18F-Flutemetamol PET/MRI

EXPERIMENTAL

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

Drug: 18F-Flutemetamol PET/MRI

Interventions

18F-Flutemetamol PET/MRIDRUG

All patients will undergo a PET/MRI of the carotids after 18F-Flutemetamol injection.

18F-Flutemetamol PET/MRI18F-Flutemetamol PET/MRI CEA18F-Flutemetamol PET/MRI dynamic

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Maastricht University Medical Centre (MUMC+)

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

MeSH Terms

Conditions

AtherosclerosisAlzheimer Disease

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesDementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 19, 2017

First Posted

September 25, 2017

Study Start

February 1, 2018

Primary Completion

December 31, 2019

Study Completion

December 31, 2019

Last Updated

July 11, 2019

Record last verified: 2019-01

Locations

NL(1)