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Myocardial Perfusion and Fibrosis in Cancer Survivors

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ClinicalTrials.gov Identifier: NCT03191461
Recruitment Status : Suspended (Investigator moving institutions)
First Posted : June 19, 2017
Last Update Posted : March 7, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:
This is a cross-sectional pilot study. The investigators seek to obtain early information pertaining to the relationship between measurements of myocardial perfusion reserve and myocardial fibrosis after receipt of Anthracycline-based chemotherapy (≥2 years prior).

Condition or disease Intervention/treatment
Myocardial Fibrosis Myocardial Injury Chemotherapeutic Toxicity Diagnostic Test: Adenosine stress test MRI

Detailed Description:

The primary objective of this cross-sectional pilot study is to determine the myocardial perfusion reserve index (MPRI) in cancer survivors treated with anthracycline chemotherapy relative to similarly aged healthy comparators without a history of cancer treatment. Hypothesis: Cancer survivors treated with anthracycline chemotherapy will have a lower MPRI than similarly aged healthy comparators without a history of cancer treatment.The secondary objective of this cross-sectional pilot study is to determine if MPRI is associated with myocardial fibrosis measured non-invasively with cardiovascular magnetic resonance imaging. Hypothesis: MPRI will be inversely associated with fibrosis burden

Study participants will be consented with pre-study data collection recorded. No randomization will occur as this is a cross-sectional study. Participants in both the cancer survivor and control groups will complete one study visit. No follow-up will be completed.


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Study Type : Observational
Estimated Enrollment : 16 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Myocardial Perfusion and Fibrosis in Cancer Survivors
Actual Study Start Date : November 13, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Adenosine

Group/Cohort Intervention/treatment
Cancer Patients
Cancer patients with Stage I-III breast cancer or lymphoma that have received an anthracycline agent during treatment at least 2 years prior to enrollment in this study. Adenosine stress test MRI will be performed.
Diagnostic Test: Adenosine stress test MRI
Participants will receive a contrasted adenosine stress CMR examination on a 1.5T Siemens Avanto scanner (Siemens Medical Solutions, Malvern, PA) dedicated to cardiovascular imaging. Adenosine stress was selected due to attenuated endothelium dependent and -independent vasodilation after doxorubicin receipt in humans to allow the investigators to understand the potential effect of perivascular fibrosis on perfusion reserve. Standardized CMR protocols will be performed to measure LV volumes (to assess wall motion abnormalities and identify any potential myocardial dysfunction), Native T1, ECV, and myocardial perfusion reserve in the short-axis plane
Other Names:
  • MRI
  • Stress Test

Healthy Controls
Age-matched Healthy Control to cancer survivor with no history of cancer or anthracycline treatment. Adenosine stress test MRI will be performed.
Diagnostic Test: Adenosine stress test MRI
Participants will receive a contrasted adenosine stress CMR examination on a 1.5T Siemens Avanto scanner (Siemens Medical Solutions, Malvern, PA) dedicated to cardiovascular imaging. Adenosine stress was selected due to attenuated endothelium dependent and -independent vasodilation after doxorubicin receipt in humans to allow the investigators to understand the potential effect of perivascular fibrosis on perfusion reserve. Standardized CMR protocols will be performed to measure LV volumes (to assess wall motion abnormalities and identify any potential myocardial dysfunction), Native T1, ECV, and myocardial perfusion reserve in the short-axis plane
Other Names:
  • MRI
  • Stress Test




Primary Outcome Measures :
  1. Myocardial perfusion reserve index (MPRI) [ Time Frame: During Adenosine Stress Test ]
    The myocardial perfusion reserve index (MPRI) will be measured noninvasively with adenosine stress CMR imaging after dual-bolus first-pass perfusion with gadolinium contrast. The slope of the myocardial signal intensity curve is computed and normalized by the slope of the blood pool signal intensity curve for both rest and stress. MPRI is calculated as the ratio of the stress slope divided by the rest slope.


Secondary Outcome Measures :
  1. Myocardial fibrosis quantification using Myocardial T1 [ Time Frame: During Adenosine Stress Test ]
    Measured noninvasively with CMR imaging. For myocardial fibrosis quantification with T1 endocardial and epicardial contours are drawn to delineate the myocardium; mean T1 (pre- and post-contrast) is calculated from the pixels within the myocardium. Expected range of T1 is 900-1250ms with higher T1 values considered a worsened outcome.

  2. Myocardial fibrosis quantification using extracellular volume (ECV) [ Time Frame: During Adenosine Stress Test ]
    Measured noninvasively with CMR imaging. The ECV is calculated from the mean myocardial T1 and LV blood T1 pre- and post-contrast. Expected range of ECV is 20-40% with higher ECV values representing a worse outcome.



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Ages Eligible for Study:   21 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The investigators will enroll 10 eligible and consenting men and women aged 21-85 years who either currently have or have had cancer who began their cancer treatment at least 2 years prior to this study and have received anthracycline based chemotherapy. The investigators will enroll an additional group of 6 men and women without cancer or a prior history of a cardiovascular event, matched to 5-year age range with our post-cancer treatment participants
Criteria

Inclusion Criteria :

  1. Cancer patients must have Stage I-III breast cancer or lymphoma and have received an anthracycline agent during treatment at least 2 years prior to enrollment in this study.
  2. Age-matched to cancer survivor with no history of cancer or anthracycline treatment.
  3. Age 21-85 years of age at the time of enrollment.
  4. ECOG or Karnofsky performance status of 0-1.
  5. Life expectancy of greater than 3 months.
  6. Enrolled control participants must have normal creatinine clearance of >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  7. Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).

Exclusion Criteria :

  1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gadolinium contrast agents or adenosine or history of kidney disease.
  2. Those with contraindications for MRI such as ferromagnetic cerebral aneurysm clips or other intracranial metal, pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices.
  3. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  4. Pregnant women are excluded from this study because the use of gadolinium in cardiac MRI imaging may not be safe in pregnant women. Because some methods of birth control are not 100% reliable, a pregnancy test is required if the participant is a) a sexually active woman of childbearing potential or b) a sexually active peri or post-menopausal women whose last normal menstrual period was less than 12 months ago.
  5. Coronary revascularization in the past 6 months or known severe multi-vessel CAD previously determined to be not amendable to mechanical intervention.
  6. Ongoing, unrelieved symptoms thought to represent cardiac ischemia and requiring immediate cardiac catheterization
  7. History of COPD or asthma

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03191461


Locations
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United States, North Carolina
Wake Forest Baptist Heath
Winston-Salem, North Carolina, United States, 27157
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23284
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: Jennifer H Jordan, PhD jenjorda@wakehealth.edu

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03191461     History of Changes
Other Study ID Numbers: IRB00044198
First Posted: June 19, 2017    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Keywords provided by Wake Forest University Health Sciences:
Anthracycline-based chemotherapy
Anth-bC
Chemotherapy
Myocardial Perfusion
Additional relevant MeSH terms:
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Adenosine
Fibrosis
Pathologic Processes
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action