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Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury

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ClinicalTrials.gov Identifier: NCT02933034
Recruitment Status : Completed
First Posted : October 14, 2016
Results First Posted : February 17, 2020
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
General Electric
Information provided by (Responsible Party):
Phillip C. Yang, MD, Stanford University

Tracking Information
First Submitted Date  ICMJE October 11, 2016
First Posted Date  ICMJE October 14, 2016
Results First Submitted Date  ICMJE February 1, 2020
Results First Posted Date  ICMJE February 17, 2020
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE April 2015
Actual Primary Completion Date February 3, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2020)
Infarct Size of MEMRI Versus DEMRI Scans [ Time Frame: Day of MEMRI and DEMRI scans (up to 3 hours per scan, performed on the same day or up to 7 days apart) ]
MEMRI is an assessment of non-viable myocardial tissue and evaluates core infarct size. DEMRI is an assessment of fibrotic tissue and evaluates the total infarct size. The difference between these two measurements evaluates the size of peri-infarct region consisting of mixed components of injured but viable cardiomyocytes and fibrosis.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
Comparison of myocardial infarction size measurements using investigational manganese-enhanced MRI (MEMRI) or delayed gadolinium enhanced MRI (DEMRI), and correlation with long-term outcomes [ Time Frame: 1 YEAR FOLLOW-UP AFTER INITIAL IMAGING TESTING ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2020)
  • Systolic Blood Pressure [ Time Frame: Before, during, and after MEMRI scan (up to 3 hours) ]
    Systolic blood pressure during MEMRI scan as a measure of manganese contrast reagent safety. Normal reference range: 90-120 mmHg.
  • Diastolic Blood Pressure [ Time Frame: Before,during, and after MEMRI scan (up to 3 hours) ]
    Diastolic blood pressure during MEMRI scan as a measure of manganese contrast reagent safety. Normal reference range: 60-80 mmHg.
  • Heart Rate [ Time Frame: Before,during, and after MEMRI scan (up to 3 hours) ]
    Heart rate during MEMRI scan as a measure of manganese contrast reagent safety. Normal reference range: 60 and 100 beats per minute.
  • QT Interval [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    QT interval during MEMRI scan as a measure of manganese contrast reagent safety. QT is a measurement of heart function that is dependent on heart rate, so QTc is mainly used for diagnosis rather than QT. Normal reference range was considered to be 360-450 milliseconds for this study.
  • Corrected QT (QTc) [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    Corrected QT (QTc) interval during MEMRI scan as a measure of manganese contrast reagent safety. QTc is a measurement of heart function and is mainly used for diagnosis rather than QT, because QT is dependent on heart rate. Normal reference range was considered to be 360-450 milliseconds for this study.
  • Alanine Aminotransferase (ALT) [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    ALT levels during MEMRI scan as a measure of manganese contrast reagent safety. ALT is a measurement of liver function. Normal reference range was considered to be <60 U/L for this study.
  • Aspartate Aminotransferase (AST) [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    AST levels during MEMRI scan as a measure of manganese contrast reagent safety. AST is a measurement of liver function. Normal reference range was considered to be <40 U/L for this study.
  • Alkaline Phosphatase (ALP) [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    ALP levels during MEMRI scan as a measure of manganese contrast reagent safety. ALP is a measurement of liver function. Normal reference range was considered to be <40-130 U/L for this study.
  • Total Bilirubin [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    Total bilirubin levels during MEMRI scan as a measure of manganese contrast reagent safety. Total bilirubin is a measurement of liver function. Normal reference range was considered to be <1.4 mg/dL for this study.
  • Creatinine [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    Creatinine levels during MEMRI scan as a measure of manganese contrast reagent safety. Creatinine is a measurement of kidney function. Normal reference range was considered to be 0.50-1.20 mg/dL for this study.
  • Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Before and after MEMRI scan (up to 3 hours) ]
    eGFR levels during MEMRI scan as a measure of manganese contrast reagent safety. eGFR is a measurement of kidney function. Normal reference range was considered to be >60 ml/min/1.73m^2 for this study.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
Safety and tolerability of manganese contrast reagent [ Time Frame: 1 day ]
Subjects undergo EKG testing pre- and post both MRI to assess any adverse symptoms or signs. The post EKG was performed after both DEMRI and MEMRI scan were complete
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury
Official Title  ICMJE Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury
Brief Summary The purpose of this study is to evaluate the safety and tolerance of a new intravenous diagnostic agent, SeeMore or EVP 1001-1, in patients with Cardiovascular Disease (MEMRI scan). The initial phase of this study, NCT01989195 enrolling a total of 6 patients, has been closed. This second phase adds 10 patients in a safety cohort and 60 additional patients for a total of 70 patients.
Detailed Description

This is an open-label, baseline-controlled study to be conducted. Adult male or nonpregnant female patients who have been referred for evaluation of dilated cardiomyopathy, ischemic cardiomyopathy, non-ischemic cardiomyopathy, atrial arrhythmia and also patients who have received stem cell therapy related to both ischemic and dilated cardiomyopathy (under different trials) will be recruited. An initial cohort study of 6 patients to conduct safety evaluation was conducted before proceeding with 60 additional patients. In the initial cohort, a patient was dosed based on the Phase 1 and 2 clinical trial data evaluation completed by Eagle Vision Pharmaceutical, Inc. Subjects were excluded if they had received an investigational device within 30 days prior to administration of EVP1001-1; had a history of drug abuse or alcoholism; were taking a digitalis preparation; had a history of torsades; had New York Heart Association (NYHA) Grade IV heart failure; had abnormal liver function tests or a history of liver disease; had uncontrolled hypertension; had abnormal calcium, potassium or hemoglobin values at baseline; if they develop a cardiac arrhythmia prior to or during either of the exercise tests-- EVP1001-1 was not administered. The same parameters will apply to the new group of subjects.

Prior to entry into this study, all subjects will sign an Informed Consent and will undergo a physical examination including medical history, details regarding their cardiac history, prescription and over-the-counter drug questionnaire, vital signs, electrocardiogram (ECG), evaluation of the major organ systems, hematology, serum chemistries, and urinalysis. In addition, female subjects will undergo a serum pregnancy test.

Starting 30 minutes before the cardiac MRI scan (CMR), the subjects will take a 16 mg tablet of ondansetron by mouth. CMR imaging will subsequently take place and then EVP1001-1 will then be administered approximately 15 minutes into the scan for contrast enhanced images. EVP1001-1 will be administered intravenously over approximately one minute. The subjects will each receive 0.28 mL/kg of EVP 1001-1. All subjects will be monitored closely from before ondansetron administration until their discharge from the imaging center. Following MEMRI, delayed-enhanced MRI (DEMRI scan) is performed using 0.2 mmol/kg.

We will compare the two different contrast enhanced images (EVP1001-1 vs gadolinium (GD)) in determining the non-viable (infarct core), peri-infarct, and total infarct size of myocardial tissue.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE ISCHEMIC CARDIOMYOPATHY
Intervention  ICMJE
  • Drug: Manganese-enhanced MRI contrast reagent
    MRI using manganese-enhanced MRI contrast reagent (manganese 0.28 mL/kg).
    Other Name: EVP 1001-1
  • Drug: Gadolinium-enhanced MRI contrast reagent
    MRI using gadolinium-enhanced MRI contrast reagent (gadolinium 0.2 mmol/kg).
    Other Name: GD-DTPA
Study Arms  ICMJE Experimental: Coronary Disease
Participant receive 2 cardiac MRI procedures: MEMRI and DEMRI.
Interventions:
  • Drug: Manganese-enhanced MRI contrast reagent
  • Drug: Gadolinium-enhanced MRI contrast reagent
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2020)
33
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2016)
70
Actual Study Completion Date  ICMJE February 3, 2019
Actual Primary Completion Date February 3, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

All subjects to be entered must:

  • be at least 18 years of age.
  • if female, be nonpregnant as evidenced by a serum pregnancy test and using a medically-approved method of birth control, or post-menopausal or surgically sterile
  • provide written informed consent after having received oral and written information about the study
  • be in stable health based on medical history, examination and tests

Exclusion Criteria:

have a positive pregnancy test (females)

  • received an investigational drug or device within 30 days prior to administration of SeeMore
  • have known hypersensitivity to ondansetron or other selective serotonin 5HT3 receptor blockers
  • have a history of drug abuse or alcoholism
  • are taking a digitalis preparation or calcium channel blocker
  • have a history of torsades or prolonged QT/QTc interval
  • have NYHA Grade IV heart failure
  • have abnormal liver function tests or a history of liver disease
  • have uncontrolled hypertension (Systolic Blood Pressure > 140 or Diastolic BP > 90 consistently at baseline)
  • have abnormal baseline potassium or calcium values or hemoglobin less than 10 g/dl
  • are noncompliant or otherwise unlikely to perform as required by the protocol
  • have pretest likelihood of CAD for which the requisite number of subjects have been entered
  • develop an arrhythmia prior to or during either of the exercise tests; SeeMore should not be administered.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02933034
Other Study ID Numbers  ICMJE 28508
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Phillip C. Yang, MD, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE General Electric
Investigators  ICMJE
Principal Investigator: Phillip C Yang, MD Stanford University
PRS Account Stanford University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP