Clinical trial NCT01724749: Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT
Official title: Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT: The CAMONA Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cardiovascular Disease
Atherosclerosis
Angina Pectoris
Keywords: Atherosclerosis
Sodium-Fluoride
18F-Sodium Fluoride
18F-NaF
fluorodeoxyglucose
18F-FDG
FDG
Positron emission tomography
PET
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2012-11-12
Enrollment: 144
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy control subjects will be recruited from a random sample of Danish citizens. To secure timely inclusion of healthy controls, blood donors will be approached for inclusion as well.

Subjects with symptoms suggesting angina pectoris will be recruited from the Department of Cardiology, Odense University Hospital. Each patient referred for symptoms suggesting angina pectoris and eligibility for a coronary artery calcium scoring (CACS) will be eligible for inclusion in the investigators study.

Brief summary: The purpose of the CAMONA study is to demonstrate the feasibility of cardiovascular molecular calcification (CMC) assessment by means of 18F-sodium-fluoride (18F-NaF) positron emission tomography (PET) computed tomography (CT) in a prospective cohort of healthy control subjects and subjects with cardiovascular disease.

Detailed description: Atherosclerosis associated cardiovascular disease (CVD) remains a significant cause of morbidity and mortality. Asymptomatic individuals with a moderate to high-risk of developing acute atherosclerotic cardiovascular events will benefit most from intensive evidence-based medical interventions.

The traditional approach to identify patients with moderate to high-risk of CVD involves quantifying the presence of CVD risk factors. Based on gender, age, smoking, systolic blood pressure and cholesterol levels, risk stratification algorithms such as the Framingham Risk Score (FRS) and the European SCORE system can predict the 10-year risk of cardiovascular death.

However, these algorithms are associated with several limitations, including misclassification of women and individuals with high levels of a single risk factor. The risk is underestimated in these individuals. Therefore, these individuals are not eligible for treatment by current criteria of CVD prevention guidelines. Several studies indicate that the traditional risk score models leave room for improvement, as they work reasonably well for populations, but remain suboptimal for individual subjects.

New risk parameters are discovered on a regular basis. One of these parameters is cardiovascular molecular calcification (CMC). This entity can be detected and quantified by 18F-NaF PET CT. It has been hypothesized that CMC can be detected years, maybe even decades, before coronary artery calcium scoring (CACS) can be detected by conventional imaging modalities like multislice CT. Theoretically, this tool can detect patients at a very early stage of the disease. Providing evidence-based treatment to these individuals can, theoretically, improve the prevention of CVD. Before this hypothesises can be tested, the feasibility of 18F-NaF PET CT has to be demonstrated in both healthy controls as well as in subjects with cardiovascular disease.

Eligibility criteria: Inclusion Criteria:

* Age: 21 - 80 years
* Healthy controls: No prior history or symptoms of cardiovascular disease
* Cardiology subjects: Eligibility for CACS due to symptoms suggesting angina pectoris.
* Cardiology subjects: HeartSCORE \> 0%.

Exclusion Criteria:

* Pregnancy
* Extensive physical activity or extensive partying passed 24 hours
* History of malignant neoplasms with past 5 years
* Known immunodeficiencies
* History of deep vein thrombosis or acute pulmonary embolism within the previous three months
* History of alcohol abuses, illicit drug use, or drug abuse, or significant mental illness
* Initiation of statin-therapy within 3 months prior to consideration of study enrolment
* History of autoimmune disease, such as systemic lupus erythematosus, inflammatory bowel disease, sarcoidosis, rheumatoid arthritis, or psoriasis.
* Participation in any clinical trial of an investigational drug, device, or medical procedure within 30 days prior to baseline of the study
* Enrolment or planned enrolment in another clinical trial during the study period

Primary outcomes:
measure: Standardized uptake value (SUV) of 18F-NaF
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Target to background ratio (TBR) of 18F-NaF
timeFrame: Up to 7 days after the day of PET CT acquisition
Secondary outcomes:
measure: Standardized uptake value (SUV) of 18F-Fluorodeoxyglucose (18F-FDG)
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Target to background ratio (TBR) of 18F-FDG
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Correlation between the TBR of 18F-NaF/18F-FDG and traditional cardiovascular risk factors.
timeFrame: The cardiovascular risk factors will be determined, on average, 1 hour before 18F-NaF / 18F-FDG injection; which ever comes first
measure: Correlation between the TBR of 18F-NaF/18F-FDG and blood markers of atherosclerosis.
timeFrame: The blood draw will be performed, on average, 1 hour before the 18F-FDG PET CT scan and the blood markers will determined in upto 48 hours after the 18F-FDG PET CT scan
measure: Correlations between 18F-NaF TBR, 18F-FDG TBR, and CT calcification scoring
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Target to background ratio (TBR) of 18F-NaF
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Target to background ratio (TBR) of 18F-FDG
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Correlation between 18F-NaF / 18F-FDG uptake and 18F-FDG uptake in the brain
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Correlation between 18F-NaF TBR and 18F-NaF TBR two years after the baseline scan.
timeFrame: 2 years
measure: Correlation between 18F-FDG TBR and 18F-FDG TBR two years after the baseline scan.
timeFrame: 2 years
measure: Correlation between the TBR of 18F-NaF/18F-FDG and HeartSCORE
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Correlation between the TBR of 18F-NaF/18F-FDG and Framingham Risk Score
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Correlation between 18F-NaF / 18F-FDG uptake and 18F-NaF / 18F-FDG uptake in the vertebral body
timeFrame: Up to 7 days after the day of PET CT acquisition
measure: Arterial Calcification Score
timeFrame: Up to 7 days after the day of PET CT acquisition
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Department of Cardiology, Odense University Hospital
state: Region Syddanmark
city: Odense
country: Denmark
facility: Department of Nuclear Medicine, Odense University Hospital
state: Region Syddanmark
Study officials:
affiliation: Odense University Hospital
name: Poul F Høilund-Carlsen, MD, DMSc
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Björn A Blomberg, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sorci O, Batzdorf AS, Mayer M, Rhodes S, Peng M, Jankelovits AR, Hornyak JN, Gerke O, Hoilund-Carlsen PF, Alavi A, Rajapakse CS. 18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification. Eur J Nucl Med Mol Imaging. 2020 Jul;47(7):1678-1687. doi: 10.1007/s00259-019-04590-3. Epub 2019 Nov 16.
citation: Pourhassan Shamchi S, Khosravi M, Taghvaei R, Zirakchian Zadeh M, Paydary K, Emamzadehfard S, Werner TJ, Hoilund-Carlsen PF, Alavi A. Normal patterns of regional brain 18F-FDG uptake in normal aging. Hell J Nucl Med. 2018 Sep-Dec;21(3):175-180. doi: 10.1967/s002449910902. Epub 2018 Nov 10.