Computed Tomography and Biomarker Analysis in Diagnosing Coronary Artery Disease in Asymptomatic Patients Who Have Undergone Stem Cell Transplant

Assessment of Coronary Artery Disease in Asymptomatic Survivors of Allogeneic Hematopoietic Cell Transplantation (HCT): A Pilot Feasibility Study

This pilot clinical trial studies computed tomography (CT) scans and biomarker analysis in diagnosing coronary artery disease (CAD) in patients who have undergone a stem cell transplant but have no symptoms of CAD. CAD is a disease in which there is a narrowing or blockage of the coronary arteries (blood vessels that carry blood and oxygen to the heart) and patients who have undergone a stem cell transplant are at an especially high risk for CAD. A CT scan involves a series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Studying samples of blood from patients who have undergone a stem cell transplant in the laboratory may help doctors identify and learn more about biomarkers related to CAD. Using a CT scan in combination with biomarker analysis may be a better and less-invasive way to diagnose CAD.

Study Overview

• Status: Completed
• Conditions: Hypertension; Diabetes Mellitus; Cancer Survivor
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: questionnaire administration; Procedure: computed tomography; Other: cytology specimen collection procedure

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate the feasibility of using CT-based imaging and blood biomarkers for assessment of asymptomatic coronary artery disease (CAD) in survivors of allogeneic hematopoietic stem cell transplant (HCT).

SECONDARY OBJECTIVES:

I. Determine the prevalence and severity of asymptomatic CAD, as measured by CT angiography.

II. Describe the association between patient demographics (age, sex, race/ethnicity), pre-HCT chest radiation, HCT-related exposures (total body irradiation [TBI], conditioning chemotherapy), graft-versus-host disease (GvHD) and its management and cardiovascular risk factors (CVRFs) on extent of CAD.

III. Describe the association between asymptomatic CAD and candidate blood biomarkers of vessel injury and inflammation (high-sensitivity C-reactive protein [hs-CRP], lipoprotein-associated phospholipase A2 [Lp-PLA2]).

OUTLINE:

Patients undergo cardiac CT and collection of blood samples for analysis of hs-CRP via quantitative immunoturbidimetry and Lp-PLA2 via enzyme-linked immunosorbent assay (ELISA).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Alive and in complete remission at time of enrollment
• Underwent allogeneic HCT after 1995
• Time between HCT and study entry: >= 2 years
• Have at least one CVRF (hypertension, diabetes, dyslipidemia) at the time of eligibility determination

Exclusion Criteria:

• History of ischemic heart disease, stroke, or cardiomyopathy/congestive heart failure
• Abnormal renal function (glomerular filtration rate [GFR] < 60 mL/min/1.73m2)
• Pregnancy
• Known allergy to intravenous (IV) contrast
• Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device; significant conduction defects (i.e.: second or third degree atrioventricular block or sick sinus syndrome)
• Current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (i.e.: asthma) requiring therapy
• History of drug sensitivity or allergic reaction to beta-blockers
• Currently taking calcium channel blockers such as verapramil and diltiazem
• History of unrepaired severe aortic stenosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diagnostic (CT and blood biomarkers); Patients undergo cardiac CT and collection of blood samples for analysis of hs-CRP via quantitative immunoturbidimetry and Lp-PLA2 via ELISA.	Other: laboratory biomarker analysis; Correlative studies; Other: questionnaire administration; Ancillary studies; Procedure: computed tomography; Undergo cardiac CT; Other Names: tomography, computed; Other: cytology specimen collection procedure; Undergo collection of blood samples; Other Names: cytologic sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility, defined by the percentage of patients that enroll onto the study, successful completion of all study measurements, ability of studies to be interpreted, and achievement of the recruitment goal	The current protocol will be considered feasible if: 1) >= 30% of eligible patients that are approached for participation enroll onto the study, 2) >= 75% enrolled participants successfully complete all study measurements (history/physical examination, blood draw, completion of study questionnaires, CT-imaging), 3) >= 90% of CT-based studies can be interpreted and 4) =< 100 individuals are approached to achieve recruitment goal of 20 participants.	Up to 9 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of asymptomatic CAD, as measured by CT angiography	Asymptomatic CAD will be defined as having either an abnormal coronary artery calcium (CAC) (>= 100 Au) or more than minimal coronary luminal stenosis (>= 30%) in any of the arteries. Descriptive statistics will be generated to characterize the extent of luminal stenosis in the study populations.	Up to 9 weeks
Severity of asymptomatic CAD, as measured by CT angiography	Asymptomatic CAD will be defined as having either an abnormal coronary artery calcium (CAC) (>= 100 Au) or more than minimal coronary luminal stenosis (>= 30%) in any of the arteries. Descriptive statistics will be generated to characterize the extent of luminal stenosis in the study populations.	Up to 9 weeks
Patient demographics (age, sex, race/ethnicity)	Will be evaluated using descriptive statistics.	Up to 9 weeks
Pre-HCT chest radiation	Will be evaluated using descriptive statistics.	Up to 9 weeks
HCT-related exposures (TBI, conditioning chemotherapy)	Will be evaluated using descriptive statistics.	Up to 9 weeks
Management of GvHD	Will be evaluated using descriptive statistics.	Up to 9 weeks
CVRF-specific characteristics	Will be evaluated using descriptive statistics.	Up to 9 weeks
Expression of hs-CRP	Standard descriptive statistics will be utilized to derive the median, mean, standard deviation, and range of individual blood biomarkers in survivors with and without CAD.	Up to 9 weeks
Expression of Lp-PLA2	Standard descriptive statistics will be utilized to derive the median, mean, standard deviation, and range of individual blood biomarkers in survivors with and without CAD.	Up to 9 weeks

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Saro Armenian, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: February 28, 2014
• First Posted (ESTIMATE): March 4, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): April 21, 2015
• Last Update Submitted That Met QC Criteria: April 17, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 13385 (OTHER: City of Hope Medical Center); NCI-2014-00419 (REGISTRY: CTRP (Clinical Trial Reporting Program))