ISCHEMIC CARDIOMYOPATHYPhase 1/2NCT01989195
Efficacy of EVP 1001-1 (SeeMore) in the Assessment of Myocardial Viability in Patients With Cardiovascular Disease
A Phase 1/2 study testing 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENT in people with ISCHEMIC CARDIOMYOPATHY, run by Stanford University at 1 site in United States.
Trial summary
The investigator hopes to introduce a novel MRI contrast agent with SeeMore ™ that directly defines viable myocardium. Identifying viable myocardium non-invasively using cardiac MRI is still a moving target and a question we plan to answer more definitively with the SeeMore ™ contrast. 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?
- 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Jun 2013
- 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 investigator hopes to introduce a novel MRI contrast agent with SeeMore ™ that directly defines viable myocardium. Identifying viable myocardium non-invasively using cardiac MRI is still a moving target and a question we plan to answer more definitively with the SeeMore ™ contrast. Though well tested in small and large animals and Phase I \& II clinical trials, the investigators would like to determine the efficacy of the SeeMore contrast further in a clinical setting.
SeeMore is a new manganese (Mn)-based intravenous imaging agent being developed to enhance magnetic resonance imaging (MRI). While Mn has long been known to have desirable magnetic and kinetic properties for MRI, use in humans was not initially possible due to cardiovascular depression and electrocardiogram (ECG) changes, including prolongation of PR and QTc intervals, associated with intravenous administration [1-5]. SeeMore provides Mn in a form that maintains the desired magnetic and kinetic properties while overcoming the cardiovascular toxicity of Mn. SeeMore is taken up into heart cells (primarily via addition of calcium to avoid cardiotoxic effects; please refer to US patent #5,980,863). The potential to distinguish healthy heart tissue from unhealthy heart tissue based on a specific sustained pattern of enhancement provides a basis for evaluating the performance of SeeMore in heart patients. It may be possible to enhance the utility of MRI for heart disease through the use of an imaging agent that is specifically taken up into heart cells. SeeMore is the only cardiac-specific agent being developed for this purpose. Unlike nuclear perfusion agents, SeeMore is not radioactive and does not require special handling, shielding, transport or storage. In addition, the specific pattern of enhancement achieved in the heart muscle persists over time, offering potential benefits over the nonspecific extracellular agents currently available for MRI or X-ray/CT procedures. This feature allows full use of the high resolution of MRI, since there is not a trade-off of high spatial resolution for temporal (first-pass) resolution. It is anticipated the features offered by SeeMore along with the high resolution, three dimensional attributes of MRI will result in higher accuracy than is available with other current modalities in practice, including stress echocardiograms, cardiac MRI using gadolinium contrast and nuclear studies such as SPECT and PET. This will be evaluated in this study and serve as the basis for pivotal registration studies.
All components of SeeMore™ are USP and are approved for use as drugs in man, orally and/or intravenously.
Read the detailed description
This is an open-label, baseline-controlled study. An initial cohort study of patients to conduct safety evaluation will be conducted before proceeding with the additional patients. In this initial cohort, a patient will be dosed based on the Phase 1 and 2 clinical trial data evaluation completed by Eagle Vision Pharmaceutical, Inc.
Starting 30 minutes before the cardiac MRI scan (CMR), the subjects will take a 4 mg tablet of ondansetron by mouth. CMR will subsequently take place and SeeMore™ will then be administered approximately 15 minutes into the scan for contrast enhanced images. SeeMore™ will be administered intravenously over approximately one minute. The subjects will each receive 0.28 mL/kg of SeeMore™. All subjects will be monitored closely from before ondansetron administration until their discharge from the imaging center. If positive delayed-enhanced MRI is detected, the subject will undergo MEMRI within 1 week. The investigators plan to perform imaging with CMR and SeeMore™ within a week after standard gadolinium-based delayed enhanced imaging by CMR (performed as clinically indicated within Stanford Hospital by the patient's physician) to directly compare the two different contrast enhanced images (SeeMore vs Gadolinium in determining viable myocardium).
Parameters to be Measured:
A standard physical examination will be performed within 24 hours prior to dosing and at the end of experimental MEMRI imaging (approximately 1 hour post dosing). A standard 12-lead EKG will be performed both before the experimental MR study and after the experimental MR study to assure no significant EKG changes have occurred. HR will be measured before and after the study. After the study, the patient will have another standard 12-lead EKG performed to compare with the pre-MRI 12-lead EKG. The patient's symptoms will be reassessed 1 hour and 1 year after infusion of the SeeMore contrast. Adverse events (AEs) and discomforts will be recorded until discharge from the imaging center. Any clinically relevant changes from baseline in vital signs, ECG rhythm, clinical chemistries or physical condition and all AEs will be followed until resolution or until the outcome is known. Primary efficacy will be based on determining whether the heart is normal or abnormal and if abnormal whether there is an infarction, ischemia or both. This provides the basis for calculating sensitivity, specificity, accuracy and predictive values. In addition, the location, size, conspicuity and associated confidence for any disease will be recorded.
The study will be stopped for any significant adverse cardiovascular event including cardiovascular death, myocardial infarction, ventricular arrhythmia, ICD firing, congestive heart failure, hospitalization, or syncope.
- Conditions
- ISCHEMIC CARDIOMYOPATHY
- Being tested
- 'SEEMORE' - MANGANESE-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.
'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENTDrug
EACH SUBJECT UNDERWENT 2 CARDIAC MRI PROCEDURES: ONE WITH MAGNEVIST (GADOLINIUM), ONE WITH SEEMORE (MANGANESE) REAGENT
- CARDIAC MRI USING STANDARD DOSE OF 0.2mMOL/KG MAGNEVIST IV (IN THE VEIN)
- CARDIAC MRI USING SEEMORE REAGENT, DOSE: 0.35CC/KG IV (IN THE VEIN) 1 WEEK AFTER GADOLINIUM MRI
| Study group | Role | What they receive |
|---|---|---|
| CORONARY DISEASE SUBJECT | Experimental | ALL SUBJECTS IN THIS STUDY HAVE PREVIOUSLY DOCUMENTED CORONARY ARTERY DISEASE BY ANGIOGRAPHY Receives: Drug: 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENT |
What is being measured
The primary outcome is the main question the study is designed to answer.
COMPARISON OF MYOCARDIAL INFARCTION SIZE MEASUREMENTS USING INVESTIGATIONAL MANGANESE-ENHANCED MRI (MEMRI) OR DELAYED GADOLINIUM ENHANCED MRI (DEMRI)
Measured as percentage of myocardial injury volume to the total left ventricular myocardial volume
Measured: Day 1 (1 MRI)
Secondary outcomes (3)
SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT
QRS Duration: SUBJECTS UNDERWENT PRE- AND POST-MRI EKG TESTING TO ASSESS ANY ADVERSE SYMPTOMS OR SIGNS. THE POST EKG WAS PERFORMED AFTER MEMRI SCAN WERE COMPLETE. EKG WAS NOT OBTAINED BEFORE AND AFTER DEMRI.
Measured the difference in heart rate per EKG before and after MEMRI study.
Measured: Pre MRI and Post MRI on same day (Day 1)
Significant Cardiovascular Event
Hospitalization and procedures for chest pain, arrhythmias, and all-cause mortality
Measured: 1 year
Heart Rate: SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT
SUBJECTS UNDERWENT PRE- AND POST-MRI EKG TESTING TO ASSESS ANY ADVERSE SYMPTOMS OR SIGNS. THE POST EKG WAS PERFORMED AFTER MEMRI SCAN WERE COMPLETE. EKG WAS NOT OBTAINED BEFORE AND AFTER DEMRI.
Measured the difference in heart rate per EKG before and after MEMRI study.
Measured: Pre MRI and Post MRI on same day (Day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2013 (estimated)
- Study startMay 2013
- Primary completionJun 2013
- Study completionJun 2013
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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- 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
- NCT01989195
- Sponsor's protocol ID
- 24224
- Status last verified
- Nov 2016
- First submitted
- 12 Nov 2013
- Last updated
- 2 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of EVP 1001-1 (SeeMore) in the Assessment of Myocardial Viability in Patients With Cardiovascular Disease
- ClinicalTrials.gov ID
- NCT01989195
- Acronym / sponsor ID
- 24224
- 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
- 6 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 20 Nov 2013 (estimated)
- Results
- Posted 2 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigator hopes to introduce a novel MRI contrast agent with SeeMore ™ that directly defines viable myocardium. Identifying viable myocardium non-invasively using cardiac MRI is still a moving target and a question we plan to answer more definitively with the SeeMore ™ contrast. Though well tested in small and large animals and Phase I \& II clinical trials, the investigators would like to determine the efficacy of the SeeMore contrast further in a clinical setting.
SeeMore is a new manganese (Mn)-based intravenous imaging agent being developed to enhance magnetic resonance imaging (MRI). While Mn has long been known to have desirable magnetic and kinetic properties for MRI, use in humans was not initially possible due to cardiovascular depression and electrocardiogram (ECG) changes, including prolongation of PR and QTc intervals, associated with intravenous administration [1-5]. SeeMore provides Mn in a form that maintains the desired magnetic and kinetic properties while overcoming the cardiovascular toxicity of Mn. SeeMore is taken up into heart cells (primarily via addition of calcium to avoid cardiotoxic effects; please refer to US patent #5,980,863). The potential to distinguish healthy heart tissue from unhealthy heart tissue based on a specific sustained pattern of enhancement provides a basis for evaluating the performance of SeeMore in heart patients. It may be possible to enhance the utility of MRI for heart disease through the use of an imaging agent that is specifically taken up into heart cells. SeeMore is the only cardiac-specific agent being developed for this purpose. Unlike nuclear perfusion agents, SeeMore is not radioactive and does not require special handling, shielding, transport or storage. In addition, the specific pattern of enhancement achieved in the heart muscle persists over time, offering potential benefits over the nonspecific extracellular agents currently available for MRI or X-ray/CT procedures. This feature allows full use of the high resolution of MRI, since there is not a trade-off of high spatial resolution for temporal (first-pass) resolution. It is anticipated the features offered by SeeMore along with the high resolution, three dimensional attributes of MRI will result in higher accuracy than is available with other current modalities in practice, including stress echocardiograms, cardiac MRI using gadolinium contrast and nuclear studies such as SPECT and PET. This will be evaluated in this study and serve as the basis for pivotal registration studies.
All components of SeeMore™ are USP and are approved for use as drugs in man, orally and/or intravenously.
Detailed description
This is an open-label, baseline-controlled study. An initial cohort study of patients to conduct safety evaluation will be conducted before proceeding with the additional patients. In this initial cohort, a patient will be dosed based on the Phase 1 and 2 clinical trial data evaluation completed by Eagle Vision Pharmaceutical, Inc.
Starting 30 minutes before the cardiac MRI scan (CMR), the subjects will take a 4 mg tablet of ondansetron by mouth. CMR will subsequently take place and SeeMore™ will then be administered approximately 15 minutes into the scan for contrast enhanced images. SeeMore™ will be administered intravenously over approximately one minute. The subjects will each receive 0.28 mL/kg of SeeMore™. All subjects will be monitored closely from before ondansetron administration until their discharge from the imaging center. If positive delayed-enhanced MRI is detected, the subject will undergo MEMRI within 1 week. The investigators plan to perform imaging with CMR and SeeMore™ within a week after standard gadolinium-based delayed enhanced imaging by CMR (performed as clinically indicated within Stanford Hospital by the patient's physician) to directly compare the two different contrast enhanced images (SeeMore vs Gadolinium in determining viable myocardium).
Parameters to be Measured:
A standard physical examination will be performed within 24 hours prior to dosing and at the end of experimental MEMRI imaging (approximately 1 hour post dosing). A standard 12-lead EKG will be performed both before the experimental MR study and after the experimental MR study to assure no significant EKG changes have occurred. HR will be measured before and after the study. After the study, the patient will have another standard 12-lead EKG performed to compare with the pre-MRI 12-lead EKG. The patient's symptoms will be reassessed 1 hour and 1 year after infusion of the SeeMore contrast. Adverse events (AEs) and discomforts will be recorded until discharge from the imaging center. Any clinically relevant changes from baseline in vital signs, ECG rhythm, clinical chemistries or physical condition and all AEs will be followed until resolution or until the outcome is known. Primary efficacy will be based on determining whether the heart is normal or abnormal and if abnormal whether there is an infarction, ischemia or both. This provides the basis for calculating sensitivity, specificity, accuracy and predictive values. In addition, the location, size, conspicuity and associated confidence for any disease will be recorded.
The study will be stopped for any significant adverse cardiovascular event including cardiovascular death, myocardial infarction, ventricular arrhythmia, ICD firing, congestive heart failure, hospitalization, or syncope.
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 SUBJECT | Experimental | Drug: 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENTALL SUBJECTS IN THIS STUDY HAVE PREVIOUSLY DOCUMENTED CORONARY ARTERY DISEASE BY ANGIOGRAPHY |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 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 |
|---|---|---|
| 'SEEMORE' - MANGANESE-ENHANCED MRI CONTRAST REAGENTEACH SUBJECT UNDERWENT 2 CARDIAC MRI PROCEDURES: ONE WITH MAGNEVIST (GADOLINIUM), ONE WITH SEEMORE (MANGANESE) REAGENT * CARDIAC MRI USING STANDARD DOSE OF 0.2mMOL/KG MAGNEVIST IV (IN THE VEIN) * CARDIAC MRI USING SEEMORE REAGENT, DOSE: 0.35CC/KG IV (IN THE VEIN) 1 WEEK AFTER GADOLINIUM MRI | Drug | CORONARY DISEASE SUBJECT |
Primary outcome
COMPARISON OF MYOCARDIAL INFARCTION SIZE MEASUREMENTS USING INVESTIGATIONAL MANGANESE-ENHANCED MRI (MEMRI) OR DELAYED GADOLINIUM ENHANCED MRI (DEMRI)
Time frame: Day 1 (1 MRI)
Measured as percentage of myocardial injury volume to the total left ventricular myocardial volume
3 secondary outcomes
SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT
Time frame: Pre MRI and Post MRI on same day (Day 1)
Significant Cardiovascular Event
Time frame: 1 year
Heart Rate: SAFETY AND TOLERABILITY OF MANGANESE CONTRAST REAGENT
Time frame: Pre MRI and Post MRI on same day (Day 1)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 'SEEMORE' - MANGANESE-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 6 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 2 Jan 2017. 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 2 Jan 2017). 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?
COMPARISON OF MYOCARDIAL INFARCTION SIZE MEASUREMENTS USING INVESTIGATIONAL MANGANESE-ENHANCED MRI (MEMRI) OR DELAYED GADOLINIUM ENHANCED MRI (DEMRI) (time frame: Day 1 (1 MRI)). 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 2 Jan 2017.