ISCHEMIC CARDIOMYOPATHYPhase 1/2NCT02933034
Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury
A Phase 1/2 study testing Manganese-enhanced MRI contrast reagent and Gadolinium-enhanced MRI contrast reagent in people with ISCHEMIC CARDIOMYOPATHY, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- ISCHEMIC CARDIOMYOPATHY
- What is being tested?
- Manganese-enhanced MRI contrast reagent and Gadolinium-enhanced MRI contrast reagent
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 3 Feb 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
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.
Read the 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.
- Conditions
- ISCHEMIC CARDIOMYOPATHY
- Being tested
- Manganese-enhanced MRI contrast reagent, Gadolinium-enhanced MRI contrast reagent
- Keywords
- ISCHEMIC OR CORONARY HEART DISEASE, MYOCARDIAL INFARCTION, MAGNETIC RESONANCE IMAGING, DELAYED GADOLINIUM ENHANCEMENT MRI, MANGANESE-ENHANCED MRI, INFARCT VOLUME/SIZE, ALL CAUSE MORTALITY, VENTRICULAR ARRHYTHMIAS
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Manganese-enhanced MRI contrast reagentDrug
Also called EVP 1001-1
MRI using manganese-enhanced MRI contrast reagent (manganese 0.28 mL/kg).
Gadolinium-enhanced MRI contrast reagentDrug
Also called GD-DTPA
MRI using gadolinium-enhanced MRI contrast reagent (gadolinium 0.2 mmol/kg).
| Study group | Role | What they receive |
|---|---|---|
| Coronary Disease | Experimental | Participant receive 2 cardiac MRI procedures: MEMRI and DEMRI. Receives: Drug: Manganese-enhanced MRI contrast reagent; Drug: Gadolinium-enhanced MRI contrast reagent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infarct Size of MEMRI Versus DEMRI Scans
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.
Measured: Day of MEMRI and DEMRI scans (up to 3 hours per scan, performed on the same day or up to 7 days apart)
Secondary outcomes (11)
Systolic Blood Pressure
Systolic blood pressure during MEMRI scan as a measure of manganese contrast reagent safety. Normal reference range: 90-120 mmHg.
Measured: Before, during, and after MEMRI scan (up to 3 hours)
Diastolic Blood Pressure
Diastolic blood pressure during MEMRI scan as a measure of manganese contrast reagent safety. Normal reference range: 60-80 mmHg.
Measured: Before,during, and after MEMRI scan (up to 3 hours)
Heart Rate
Heart rate during MEMRI scan as a measure of manganese contrast reagent safety. Normal reference range: 60 and 100 beats per minute.
Measured: Before,during, and after MEMRI scan (up to 3 hours)
QT Interval
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Corrected QT (QTc)
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Alanine Aminotransferase (ALT)
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Aspartate Aminotransferase (AST)
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Alkaline Phosphatase (ALP)
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Total Bilirubin
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Creatinine
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Estimated Glomerular Filtration Rate (eGFR)
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.
Measured: Before and after MEMRI scan (up to 3 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study startApr 2015
- Primary completion3 Feb 2019
- Study completion3 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ISCHEMIC CARDIOMYOPATHYStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- General Electric
- Responsible party
- Principal investigator, Phillip C. Yang, MD, Stanford University
- Investigators
- Phillip C Yang, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02933034
- Sponsor's protocol ID
- 28508
- Status last verified
- Feb 2020
- First submitted
- 11 Oct 2016
- Last updated
- 17 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of Manganese-Enhanced MRI (MEMRI) to Assess Peri-Infarct Injury
- ClinicalTrials.gov ID
- NCT02933034
- Acronym / sponsor ID
- 28508
- Conditions
- ISCHEMIC CARDIOMYOPATHY
- Keywords
- ISCHEMIC OR CORONARY HEART DISEASE, MYOCARDIAL INFARCTION, MAGNETIC RESONANCE IMAGING, DELAYED GADOLINIUM ENHANCEMENT MRI, MANGANESE-ENHANCED MRI, INFARCT VOLUME/SIZE, ALL CAUSE MORTALITY, VENTRICULAR ARRHYTHMIAS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- General Electric
- Study start
- Apr 2015 (actual)
- Primary completion
- 3 Feb 2019 (actual)
- Study completion
- 3 Feb 2019 (actual)
- First posted
- 14 Oct 2016 (estimated)
- Results
- Posted 17 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Coronary Disease | Experimental | Drug: Manganese-enhanced MRI contrast reagent, Drug: Gadolinium-enhanced MRI contrast reagentParticipant receive 2 cardiac MRI procedures: MEMRI and DEMRI. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Manganese-enhanced MRI contrast reagentAlso: EVP 1001-1MRI using manganese-enhanced MRI contrast reagent (manganese 0.28 mL/kg). | Drug | Coronary Disease |
| Gadolinium-enhanced MRI contrast reagentAlso: GD-DTPAMRI using gadolinium-enhanced MRI contrast reagent (gadolinium 0.2 mmol/kg). | Drug | Coronary Disease |
Primary outcome
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.
11 secondary outcomes
Systolic Blood Pressure
Time frame: Before, during, and after MEMRI scan (up to 3 hours)
Diastolic Blood Pressure
Time frame: Before,during, and after MEMRI scan (up to 3 hours)
Heart Rate
Time frame: Before,during, and after MEMRI scan (up to 3 hours)
QT Interval
Time frame: Before and after MEMRI scan (up to 3 hours)
Corrected QT (QTc)
Time frame: Before and after MEMRI scan (up to 3 hours)
Alanine Aminotransferase (ALT)
Time frame: Before and after MEMRI scan (up to 3 hours)
Aspartate Aminotransferase (AST)
Time frame: Before and after MEMRI scan (up to 3 hours)
Alkaline Phosphatase (ALP)
Time frame: Before and after MEMRI scan (up to 3 hours)
Total Bilirubin
Time frame: Before and after MEMRI scan (up to 3 hours)
Creatinine
Time frame: Before and after MEMRI scan (up to 3 hours)
Estimated Glomerular Filtration Rate (eGFR)
Time frame: Before and after MEMRI scan (up to 3 hours)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Phillip C Yang, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Manganese-enhanced MRI contrast reagent and Gadolinium-enhanced MRI contrast reagent in people with ISCHEMIC CARDIOMYOPATHY, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.