Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT (CAMONA)

This study is currently recruiting participants.
Verified November 2012 by Odense University Hospital
Sponsor:
Information provided by (Responsible Party):
Björn A Blomberg, Odense University Hospital
ClinicalTrials.gov Identifier:
NCT01724749
First received: November 6, 2012
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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.


Condition
Cardiovascular Disease
Atherosclerosis
Angina Pectoris

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT: The CAMONA Study

Resource links provided by NLM:


Further study details as provided by Odense University Hospital:

Primary Outcome Measures:
  • Standardized uptake value (SUV) of 18F-NaF [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    The SUV is a validated semi-quantitative assessment of PET radiotracer uptake. The SUV of 18F-NaF will be determined in the aorta, carotid arteries, coronary arteries, iliac arteries and the femoral arteries.

  • Target to background ratio (TBR) of 18F-NaF [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    The TBR is a validated semi-quantitative assessment of PET radiotracer uptake. The TBR of 18F-NaF will be determined in the aorta, carotid arteries, coronary arteries, iliac arteries and the femoral arteries.


Secondary Outcome Measures:
  • Standardized uptake value (SUV) of 18F-Fluorodeoxyglucose (18F-FDG) [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    The SUV is a validated semi-quantitative assessment of PET radiotracer uptake. The SUV of 18F-FDG will be determined in the aorta, carotid arteries, iliac arteries and the femoral arteries.

  • Target to background ratio (TBR) of 18F-FDG [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    The TBR is a validated semi-quantitative assessment of PET radiotracer uptake. The TBR of 18F-FDG will be determined in the aorta, carotid arteries, iliac arteries and the femoral arteries.

  • Correlation between the TBR of 18F-NaF/18F-FDG and traditional cardiovascular risk factors. [ Time Frame: The cardiovascular risk factors will be determined, on average, 1 hour before 18F-NaF / 18F-FDG injection; which ever comes first ] [ Designated as safety issue: No ]

    The traditional cardiovascular risk factors consist of:

    1. Smoking, pack years;
    2. Alcohol, units/week;
    3. Blood pressure, mean arterial pressure, mmHg;
    4. Body mass index, kg/m2;
    5. Waist circumference, cm;
    6. History of cardiovascular disease;
    7. Family history of cardiovascular disease;
    8. Medication usage;
    9. Age;
    10. Gender.

  • Correlation between the TBR of 18F-NaF/18F-FDG and blood markers of atherosclerosis. [ Time Frame: 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 ] [ Designated as safety issue: No ]

    Blood markers:

    1. Total cholesterol, mmol/L;
    2. LDL cholesterol, mmol/L;
    3. HDL cholesterol, mmol/L;
    4. Triglycerides, mmol/L;
    5. Homocysteine, mmol/L;
    6. Fasting plasma glucose, mmol/L;
    7. HBA1c, mmol/mol;
    8. High sensitivity C-reactive protein, nmol/L;
    9. Fibrinogen, umol/L;
    10. Leukocyte differentiation, cells/L;
    11. Creatinine, umol/L;

  • Correlations between 18F-NaF TBR, 18F-FDG TBR, and CT calcification scoring [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    Correlation between the degree of 18F-NaF uptake, 18F-FDG uptake, CT-Calcification scoring and the various arterial segments (aorta, carotid arteries, iliac arteries and the femoral arteries.

  • Target to background ratio (TBR) of 18F-NaF [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    18F-NaF PET/CT images will be acquired at 45, 90 and 180 minutes after intravenous injection of the compound in a subset of 40 patients. The TBR of 18F-NaF will be determined at each time point and compared to allow determining the optimum tracer circulation time for maximum contrast between the vessel wall and blood pool.

  • Target to background ratio (TBR) of 18F-FDG [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    18F-FDG PET/CT images will be acquired at 90 and 180 minutes after intravenous injection of the compound in a subset of 40 patients. The TBR of 18F-NaF will be determined at both time points and compared to allow determining the optimum tracer circulation time for maximum contrast between the vessel wall and blood pool.

  • Correlation between 18F-NaF / 18F-FDG uptake and 18F-FDG uptake in the brain [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    18F-FDG uptake in the brain will be quantified by calculating the mean and maximum partial-volume corrected SUV.

  • Correlation between 18F-NaF TBR and 18F-NaF TBR two years after the baseline scan. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The TBR will be determined in various segments of the arterial tree.

  • Correlation between 18F-FDG TBR and 18F-FDG TBR two years after the baseline scan. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The TBR will be determined in various segments of the arterial tree.

  • Correlation between the TBR of 18F-NaF/18F-FDG and HeartSCORE [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    The HeartSCORE will be calculated according to the current HeartSCORE protocol for Denmark.

  • Correlation between the TBR of 18F-NaF/18F-FDG and Framingham Risk Score [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    The Framingham Risk Score will be calculated according to the current recommendations by the Framingham Heart Study group

  • Correlation between 18F-NaF / 18F-FDG uptake and 18F-NaF / 18F-FDG uptake in the vertebral body [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    18F-NaF uptake in the 1st, 3rd and 5th lumbar vertebral body will be quantified by calculating the mean and maximum partial-volume corrected SUV.

  • Arterial Calcification Score [ Time Frame: Up to 7 days after the day of PET CT acquisition ] [ Designated as safety issue: No ]
    Arterial Calcification Scoring will be determined in Agatston Units as well as in volumetric units in all segments of the arterial tree (coronary arteries, aorta, carotid arteries, iliac and femoral arteries.


Biospecimen Retention:   Samples Without DNA

Whole blood, serum.


Estimated Enrollment: 144
Study Start Date: November 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Healthy control subjects
  1. Age: 21 - 80 years
  2. No prior history or symptoms of cardiovascular disease

The investigators aim to include equal numbers of females and males. Furthermore, the investigators aim to include patients in six different age strata: 21-30, 31-40, 41-50, 51-60, 61-70, 71-80.

Subjects with cardiovascular disease
  1. Age: 21 - 80 years
  2. HeartSCORE > 0%
  3. Symptoms of angina pectoris

The investigators aim to include equal numbers of females and males. Furthermore, the investigators aim to include patients in six different age strata: 21-30, 31-40, 41-50, 51-60, 61-70, 71-80. Also, the investigators aim to include patients in 3 strata of HeartSCORE risk: low risk (1-4%), mild risk (5-9%) and high risk (> 9%)


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

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01724749

Contacts
Contact: Poul F Høilund-Carlsen, MD, DMSc 0045 2521 5445 pfhc@ouh.regionsyddanmark.dk
Contact: Björn A Blomberg, MD, MSc 004551648696 Bjorn.Blomberg@ouh.regionsyddanmark.dk

Locations
Denmark
Department of Nuclear Medicine, Odense University Hospital Recruiting
Odense, Region Syddanmark, Denmark, 5000
Contact: Poul F Høilund-Carlsen, MD, DMSc       pfhc@ouh.regionsyddanmark.dk   
Principal Investigator: Björn A Blomberg, MD, MSc         
Sub-Investigator: Anders Thomassen, MD         
Sub-Investigator: Malene Hildebrandt, MD, PhD         
Sub-Investigator: Søren Hess, MD         
Department of Cardiology, Odense University Hospital Recruiting
Odense, Region Syddanmark, Denmark, 5000
Contact: Axel Diederichsen, MD       Axel.Diederichsen@ouh.regionsyddanmark.dk   
Sponsors and Collaborators
Odense University Hospital
Investigators
Study Chair: Poul F Høilund-Carlsen, MD, DMSc Odense University Hospital
Principal Investigator: Björn A Blomberg, MD, MSc Odense University Hospital
  More Information

No publications provided

Responsible Party: Björn A Blomberg, MD, MSc, Odense University Hospital
ClinicalTrials.gov Identifier: NCT01724749     History of Changes
Other Study ID Numbers: s-20120056
Study First Received: November 6, 2012
Last Updated: November 7, 2012
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Odense University Hospital:
Atherosclerosis
Sodium-Fluoride
18F-Sodium Fluoride
18F-NaF
fluorodeoxyglucose
18F-FDG
FDG
Positron emission tomography
PET

Additional relevant MeSH terms:
Angina Pectoris
Atherosclerosis
Calcinosis
Cardiovascular Diseases
Myocardial Ischemia
Heart Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Calcium Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on April 17, 2014