Ignite Creation Date:
2024-05-06 @ 4:00 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04835571
Status:
COMPLETED
Last Update Posted:
2022-12-08
First Post:
2021-04-05
Brief Title:
CARotid Mri of Atherosclerosis
Sponsor:
Linkoeping University
Organization:
Linkoeping University
Study Overview
Official Title:
CARotid Mri of Atherosclerosis
Status:
COMPLETED
Status Verified Date:
2022-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CARMA
Brief Summary:
In the entire world most people die from cardiovascular disease Death is primarily from myocardial infarction MI and stroke which are most often caused by rupture of atherosclerotic plaques Patients with high-grade ie 70 carotid artery stenosis are at especially high risk Magnetic Resonance Imaging MRI studies show that two features inside plaques that are associated with the risk of plaque rupture and subsequent cardiovascular events are lipid rich necrotic core LRNC and intraplaque hemorrhage IPH
MRI studies on carotid artery plaques typically relies on proton-density-weighted fast-spin echo blood-suppressed T1- and T2-weighted gradient-echo sequences The end-result is nonquantitative measures where plaque features are identified due to their relative signal intensity To address these problems of non-specificity we developed a quantitative MRI qMRI technique based on Dixon sequences
The study intention is to enable in-depth analysis of plaque features and their relation to clinical data For example there is an insufficient understanding of associations between lipid biomarkers and plaque contents Our hypothesis is that we can identify quantitative changes in both plaque and lipid biomarkers after one year of optimized cardiovascular risk management including treatment with lipid lowering drugs and establish if there is any associations between these features Because there is a well-established link between systemic inflammation and the presence of atherosclerotic plaques we will also study the relationship between LRNC and IPH as measured by qMRI versus circulating markers of inflammation
Method Patients with known carotid stenosis are invited for a baseline visit and a 1-year follow up visit The study visits include clinical assessment blood tests patient interview and magnetic resonance imaging of the carotid arteries All participants are offered optimized cardiovascular risk management through the individual assessment by the study physicians
MRI studies on carotid artery plaques typically relies on proton-density-weighted fast-spin echo blood-suppressed T1- and T2-weighted gradient-echo sequences The end-result is nonquantitative measures where plaque features are identified due to their relative signal intensity To address these problems of non-specificity we developed a quantitative MRI qMRI technique based on Dixon sequences
The study intention is to enable in-depth analysis of plaque features and their relation to clinical data For example there is an insufficient understanding of associations between lipid biomarkers and plaque contents Our hypothesis is that we can identify quantitative changes in both plaque and lipid biomarkers after one year of optimized cardiovascular risk management including treatment with lipid lowering drugs and establish if there is any associations between these features Because there is a well-established link between systemic inflammation and the presence of atherosclerotic plaques we will also study the relationship between LRNC and IPH as measured by qMRI versus circulating markers of inflammation
Method Patients with known carotid stenosis are invited for a baseline visit and a 1-year follow up visit The study visits include clinical assessment blood tests patient interview and magnetic resonance imaging of the carotid arteries All participants are offered optimized cardiovascular risk management through the individual assessment by the study physicians
Detailed Description:
Regarding quality assurance plans that address data validation and registry procedures the current study is a single centre investigator-initiated study and therefore there are no plans for site monitoring and auditing The reliability and validity of the MRI data has been previously confirmed with comparison to 3D histology data Koppal et al Quantitative fat and R2 mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis Magn Reson Med 2017781285-96
Concerning data checks intraobserver reliability regarding baseline and follow-up measurements will be ascertained Intraclass Correlation Coefficients ICC Bland Altman
Data is collected from patient medical records electronic dedicated study record forms paper and clinical assessments resulting in quantitative measures These external data sources are transferred into a study database
The current study is a clinical study using only clinically validated laboratory parameters The source of the lab values and their normal ranges is the electronic patient record The normal ranges have been established by the clinical chemistry and haematology laboratories at Linköping University Hospital Clinical diagnosis and procedures are recorded using the International Classification of Diseases ICD classification
The study was approved by the Swedish Ethical Review Authority approval nr 2016-441-31 and performed in accordance with the Declaration of Helsinki Written informed consent has been obtained from all study participants
Patients are selected based on duplex ultrasound criteria established for the European Carotid Surgery Trial A cut-off at doppler flow velocity has been used to identify eligible patients and after considering inclusion and exclusion criteria patients have been contacted by the study clinicians dr Elin Good or dr Ebo de Muinck for recruitment Any registration for adverse events follows the same procedures as in routine care
Sample size assessment was based on results from previous studies in relation to our primary outcome variables For example one study with 24 patients and a follow-up time of three months experienced a significant reduction of lipid rich necrotic core using magnetic resonance imaging Alkhalil et al T2 mapping MRI technique quantifies carotid plaque lipid and its depletion after statin initiation following acute myocardial infarction Atherosclerosis 2018279100-6 Therefore we aimed to include 50 patients who have completed both baseline and follow-up and the follow-up time was set to 12 months
Our plan for missing data in situations where variables are missing unavailable non-reported uninterpretable etc is to not exclude the study participant in order to avoid bias For example in cases where the imaging data from one patient is lost we will still use the remaining clinical data from that patient if the patient has been included in the study
Regarding Statistical analysis SPSS Statistics 26 International Business Machines Corporation New York NY USA is used for statistical analysis Continuous variables are summarized as mean standard deviation SD To address the primary objectives the strength of the association between fat fraction FF and R2 Pearson correlation coefficient is used and Paired-samples T test is used for analysing changes in quantitative values between baseline and follow-up
Intra-observer repeatability measurements were calculated using ICC For ICC evaluation we used two-way random effect models checking for absolute agreement average measures presented
Concerning data checks intraobserver reliability regarding baseline and follow-up measurements will be ascertained Intraclass Correlation Coefficients ICC Bland Altman
Data is collected from patient medical records electronic dedicated study record forms paper and clinical assessments resulting in quantitative measures These external data sources are transferred into a study database
The current study is a clinical study using only clinically validated laboratory parameters The source of the lab values and their normal ranges is the electronic patient record The normal ranges have been established by the clinical chemistry and haematology laboratories at Linköping University Hospital Clinical diagnosis and procedures are recorded using the International Classification of Diseases ICD classification
The study was approved by the Swedish Ethical Review Authority approval nr 2016-441-31 and performed in accordance with the Declaration of Helsinki Written informed consent has been obtained from all study participants
Patients are selected based on duplex ultrasound criteria established for the European Carotid Surgery Trial A cut-off at doppler flow velocity has been used to identify eligible patients and after considering inclusion and exclusion criteria patients have been contacted by the study clinicians dr Elin Good or dr Ebo de Muinck for recruitment Any registration for adverse events follows the same procedures as in routine care
Sample size assessment was based on results from previous studies in relation to our primary outcome variables For example one study with 24 patients and a follow-up time of three months experienced a significant reduction of lipid rich necrotic core using magnetic resonance imaging Alkhalil et al T2 mapping MRI technique quantifies carotid plaque lipid and its depletion after statin initiation following acute myocardial infarction Atherosclerosis 2018279100-6 Therefore we aimed to include 50 patients who have completed both baseline and follow-up and the follow-up time was set to 12 months
Our plan for missing data in situations where variables are missing unavailable non-reported uninterpretable etc is to not exclude the study participant in order to avoid bias For example in cases where the imaging data from one patient is lost we will still use the remaining clinical data from that patient if the patient has been included in the study
Regarding Statistical analysis SPSS Statistics 26 International Business Machines Corporation New York NY USA is used for statistical analysis Continuous variables are summarized as mean standard deviation SD To address the primary objectives the strength of the association between fat fraction FF and R2 Pearson correlation coefficient is used and Paired-samples T test is used for analysing changes in quantitative values between baseline and follow-up
Intra-observer repeatability measurements were calculated using ICC For ICC evaluation we used two-way random effect models checking for absolute agreement average measures presented
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None