Atherosclerosis
Conditions
Keywords
Cancer survivorship, Cardiovascular disease, Stroke, Transient ischemic attack (TIA)
Brief summary
The goal of this study is to assess a slimy substance that settles/deposits along blood vessel wall. This slimy substance is called plaque. Plaque could be made up of fat, calcium or both. Plaque deposition narrows the vessels. This leads to decreased blood flow to various parts of body. Blood vessels include vessels that supply to heart (coronary), vessels to brain (carotid), vessels to kidneys (renal) and vessels to legs (femoral). Decreased blood flow causes symptoms such as brain stroke, heart attack, leg pain. Similarly individuals at risk of cardiovascular disease can have certain markers elevated in their blood that can be measured by simple blood tests. High or increased plaque deposition is seen in neck vessels of cancer patients who received radiation to chest or head and neck as part of their cancer treatment. Cancer survivors are at increased risk of plaque development and are therefore called high-risk population. Exercise +/- fat lowering medicine can potentially decrease plaque deposition and statins are one of the several fat lowering medications.
Detailed description
Cardiovascular disease (CVD) and cancer are the leading causes of suffering and death amongst the American population. While an ever-increasing number of cancer survivors have a favorable outcome due to advances in cancer treatment; cancer survivors remain at high risk of developing CVD at an early age. There is scant information available on the pathogenic process that contributes to cardiovascular threat amongst cancer survivors and little is known about the interventions, which may interrupt or decrease the risk of CVD in this population. Importantly, early-subclinical markers may substantially precede clinical markers. The objective of this project is to accurately determine the constituents and characteristics of atherosclerotic plaques in carotid arteries by magnetic resonance imaging (MRI) techniques in cancer survivors; at different data intervals: before and after administration of treatment (medical and life style modification) and then correlate contrast agent dynamics with serum markers of inflammation and other tests of cardiac or vascular dysfunction, where available. The proposed study involves 100 asymptomatic patients who received prior chest or head and neck radiation therapy (HNXRT) as part of cancer treatment. MRI data (direct assessment of atherosclerosis) would be correlated with indirect measures of atherosclerosis (blood surrogate markers & metabolomics). The investigators intend to conduct an initial baseline MRI, blood tests (to correlate with surrogate markers of inflammation) and other tests whenever available of cardiac or vascular dysfunction. This cohort will be followed up with medication and/or life style modification regimen for a period of initially18 months and subsequently at 36 months. A repeat of all baseline studies (MRI and blood tests) would be performed as part of the 18 and 36-month follow-up. The plaque characteristics found at MRI will be correlated with results of blood tests (baseline, 18 and 36 months) and changes in one or both will be the expected end point of the study.
Interventions
DRUGStatin therapy
Statin therapy includes rosuvastatin 20 mg administered orally, once a day, for the duration of the trial, which is 3 years. Participants may also receive a different type of statin as prescribed by their cardiologist based on clinical judgement.
BEHAVIORALLifestyle modification
Lifestyle modification includes a recommended exercise regimen, a healthy diet and decreasing alcohol intake for 3 years.
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Intervention model description
The protocol originally specified randomizing participants to a study arm, but the protocol was amended to clarify that a participant's cardiologist could change the treatment regimens that participants were assigned to so that no participant was restricted from statin therapy.
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 22 and above with prior head and neck or chest irradiation * Six months or more post head and neck irradiation * Documented subclinical cardiovascular disease (inflammatory markers in the serum) * Pre-existing plaques (detected by ultrasound, CT or MRI) * Asymptomatic major arterial stenosis * Not being considered for arterial surgery or endovascular treatment.
Exclusion criteria
* Recurrence of cancer (with or without treatment) * Planned surgical or endovascular intervention for revascularization of carotid arteries at the time of enrollment * Renal failure * Estimated glomerular filtration rate (eGFR) \< 45 (calculation based on serum creatinine levels, race, age and gender) * Medically unstable or hematologic, renal, or hepatic dysfunction * Non-atherosclerotic arterial stenosis (dissection) * Presence of stents or external clips that can cause artifacts impairing accurate interpretation of MRI data * Contraindications to MRI: cardiac pacemaker, metal implants, metal in eyes, pregnant or nursing women, claustrophobia, allergy to MRI contrast * Physical or mental impairment that would limit the patient's ability to comply with the medical instructions or study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plaque Volume of Carotid Arteries | Baseline, 18 months, 36 months | Plaque volume of carotid arteries were measured by MRI as a surrogate for progression of cardiovascular disease. Plaque volume varies with observed ranges from other studies ranging from 23.9 to 604.1mm\^3. Plaque volume tends to increase with age. Increased plaque volume has an increased risk of vascular events. |
Countries
United States
Participant flow
Pre-assignment details
A total of 11 individuals gave informed consent to participate in the study, however, one withdrew from the study and one was lost to follow up before being assigned to a study arm. These individuals are not considered as enrolled as no clinical data were collected. Nine participants were assigned to a study arm and began the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Lifestyle Modification Participants receiving information about lifestyle modifications including a recommended exercise regimen, a healthy diet and decreasing alcohol intake. | 5 |
| Statin Therapy Participants receiving statin therapy. A participant's cardiologist could change the treatment regimen that a participant was assigned to so that no participant was restricted from statin therapy. The results reflect the treatment each participant actually received rather than the treatment each participant was randomized to. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated | 5 | 4 |
Baseline characteristics
| Characteristic | Statin Therapy | Total | Lifestyle Modification |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 3 Participants |
| Age, Continuous | 62.25 years STANDARD_DEVIATION 1.7 | 61.33 years STANDARD_DEVIATION 2.06 | 60.60 years STANDARD_DEVIATION 3.64 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 0 / 5 | 0 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
Plaque Volume of Carotid Arteries
Plaque volume of carotid arteries were measured by MRI as a surrogate for progression of cardiovascular disease. Plaque volume varies with observed ranges from other studies ranging from 23.9 to 604.1mm\^3. Plaque volume tends to increase with age. Increased plaque volume has an increased risk of vascular events.
Time frame: Baseline, 18 months, 36 months
Population: This analysis includes all participants who completed the MRI at each time point. Most participants did not return for the follow up MRI measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lifestyle Modification | Plaque Volume of Carotid Arteries | Baseline | 125.18 Cubic millimeter (mm^3) | Standard Deviation 8.09 |
| Statin Therapy | Plaque Volume of Carotid Arteries | Baseline | 108.88 Cubic millimeter (mm^3) | Standard Deviation 5.27 |
| Statin Therapy | Plaque Volume of Carotid Arteries | Month 18 | 114.70 Cubic millimeter (mm^3) | Standard Deviation 0 |