Heart TransplantationMRSNCT00469911
Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy
A study testing Magnetic Resonance Spectroscopy and Ex vivo heart biopsy in people with Heart Transplantation, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Accumulation of triglycerides in heart tissue has been associated with changes in left ventricular function which can lead to heart failure. Proton magnetic resonance spectroscopy is currently the only non-invasive in vivo method to measure myocardial triglycerides content. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Transplantation
- What is being tested?
- Magnetic Resonance Spectroscopy and Ex vivo heart biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Jun 2009
- Phase
- Interventional
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy volunteers
- heart transplant patients
- undergoing post transplant endomyocardial biopsy
- not experiencing significant rejection
- heart transplant patients must be 18-30 years old.
Who cannot join
- <18 or >45
- pregnant
- significant systemic illness
- actively ill
- acute transplant rejection
- any condition that would prevent a participant from completing the NMR spectroscopy (i.e pacemakers, claustrophobia)
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University Medical School
St Louis, Missouri, 63110
About this study
Accumulation of triglycerides in heart tissue has been associated with changes in left ventricular function which can lead to heart failure. Proton magnetic resonance spectroscopy is currently the only non-invasive in vivo method to measure myocardial triglycerides content. The primary goal of this study was to determine if Magnetic Resonance Spectroscopy could effectively measure myocardial triglyceride content in myocardial heart tissue. Thus, quantitative and reliable techniques to monitor in vivo triglyceride accumulation in the heart are important for disease diagnosis and management. Currently, no such imaging method exists.
Read the detailed description
Because routine biopsy of the myocardium is not feasible, MRS is the most promising technique for the quantification of myocardial triglycerides. MRS is routinely used to precisely characterize metabolite concentrations in muscle and liver. 14-16 Studies such as monitoring the levels of deoxymyoglobin and real-time tracking of the postprandial accumulation of cellular lipids are examples of its diversity and potential.15,17,18 Generally, these studies suggest that the reproducibility of MRS is between 2 and 6%.18,19 In vivo cardiac MRS provides unique challenges because of the requirement to compensate for concurrent heart and lung motion. Using cardiac and respiratory gating to minimize motional artifacts, an initial validation study found a variation of 17% for sequential measurements, attributing the major error to residual motional effects. 20 Moreover, measurements were limited to the inter-ventricular septum. Using navigator and cardiac gating appeared to give a slight, 4%, improvement, but this was a preliminary study and no validation was done.21 For a comprehensive clinical validation, other reproducibility factors must be addressed. Variations due to post-processing, coil placement and calibration, trigger reproducibility, internal versus external standard, shimming, and protocol sequence variables such as pulse quality, gradient strength, voxel size, relaxation time, echo time, and the number of scan repetitions are all known sources of reproducibility. 17,19,22-24 All of these variables must be characterized in order to achieve optimal inter- scanner and subject reproducibility along with accurate treatment tracking capability. Therefore, 10 normal healthy volunteers were imaged to determine the reliability of the MRS protocol with test-re-test measurements. The 8 heart transplant patients were imaged prior to their routine heart biopsies, and then the myocardial biopsy tissue was measure and compared to the pre-biopsy images.
- Conditions
- Heart Transplantation
- Being tested
- Magnetic Resonance Spectroscopy, Ex vivo heart biopsy
- Keywords
- Heart, Transplant, MRS, MRI, Spectroscopy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance SpectroscopyProcedure or surgery
Also called MRS
Magnetic Resonance Spectroscopy is a noninvasive procedure that provides detailed body images on any plane.
Ex vivo heart biopsyProcedure or surgery
Also called heart biopsy
Heart transplant patients will have their normal clinical routine heart biopsy
| Study group | Role | What they receive |
|---|---|---|
| Magnetic Resonance Spectroscopy | Experimental | Patients will have Magnetic Resonance Spectroscopy to measure in vivo accumulation of triglycerides in myocardial tissue Receives: Procedure: Magnetic Resonance Spectroscopy |
| Ex vivo heart biopsy | Experimental | Patients will have their normal routine clinical heart biopsy of myocardial heart tissue. Receives: Procedure: Ex vivo heart biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation Co-efficient Between MRS Spectroscopy and Endomyocardial Biopsy in Heart Transplant Participants
Participants first had MRS spectroscopy then the MRS spectroscopy images were compared to endomyocardial biopsy
Measured: 2 to 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2007 (estimated)
- Study startAug 2005
- Primary completionJun 2009
- Study completionJun 2009
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.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Compare magnetic resonance imaging measurements of triglyceride accumulation in myocardial tissue with ex vivo myocardial tissue collected from heart transplant patients who have had routine clinical heart biopsy.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Research Resources (NCRR)
- Responsible party
- Sponsor
- Investigators
- Robert Gropler, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00469911
- Sponsor's protocol ID
- 5P20RR02064302
- Other IDs
- 05-0759, P20RR020643
- Acronym
- MRS
- Status last verified
- Sep 2018
- First submitted
- 4 May 2007
- Last updated
- 13 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8. doi: 10.1001/jama.241.19.2035.
PubMed 430798Koskinen P, Manttari M, Manninen V, Huttunen JK, Heinonen OP, Frick MH. Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care. 1992 Jul;15(7):820-5. doi: 10.2337/diacare.15.7.820.
PubMed 1516498Abbott RD, Donahue RP, Kannel WB, Wilson PW. The impact of diabetes on survival following myocardial infarction in men vs women. The Framingham Study. JAMA. 1988 Dec 16;260(23):3456-60.
PubMed 2974889Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29-34. doi: 10.1016/0002-9149(74)90089-7. No abstract available.
PubMed 4835750Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1784-9. doi: 10.1073/pnas.97.4.1784.
PubMed 10677535
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy
- ClinicalTrials.gov ID
- NCT00469911
- Acronym / sponsor ID
- MRS / 5P20RR02064302
- Conditions
- Heart Transplantation
- Keywords
- Heart, Transplant, MRS, MRI, Spectroscopy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Research Resources (NCRR)
- Study start
- Aug 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 7 May 2007 (estimated)
- Results
- Posted 13 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Accumulation of triglycerides in heart tissue has been associated with changes in left ventricular function which can lead to heart failure. Proton magnetic resonance spectroscopy is currently the only non-invasive in vivo method to measure myocardial triglycerides content. The primary goal of this study was to determine if Magnetic Resonance Spectroscopy could effectively measure myocardial triglyceride content in myocardial heart tissue. Thus, quantitative and reliable techniques to monitor in vivo triglyceride accumulation in the heart are important for disease diagnosis and management. Currently, no such imaging method exists.
Detailed description
Because routine biopsy of the myocardium is not feasible, MRS is the most promising technique for the quantification of myocardial triglycerides. MRS is routinely used to precisely characterize metabolite concentrations in muscle and liver. 14-16 Studies such as monitoring the levels of deoxymyoglobin and real-time tracking of the postprandial accumulation of cellular lipids are examples of its diversity and potential.15,17,18 Generally, these studies suggest that the reproducibility of MRS is between 2 and 6%.18,19 In vivo cardiac MRS provides unique challenges because of the requirement to compensate for concurrent heart and lung motion. Using cardiac and respiratory gating to minimize motional artifacts, an initial validation study found a variation of 17% for sequential measurements, attributing the major error to residual motional effects. 20 Moreover, measurements were limited to the inter-ventricular septum. Using navigator and cardiac gating appeared to give a slight, 4%, improvement, but this was a preliminary study and no validation was done.21 For a comprehensive clinical validation, other reproducibility factors must be addressed. Variations due to post-processing, coil placement and calibration, trigger reproducibility, internal versus external standard, shimming, and protocol sequence variables such as pulse quality, gradient strength, voxel size, relaxation time, echo time, and the number of scan repetitions are all known sources of reproducibility. 17,19,22-24 All of these variables must be characterized in order to achieve optimal inter- scanner and subject reproducibility along with accurate treatment tracking capability. Therefore, 10 normal healthy volunteers were imaged to determine the reliability of the MRS protocol with test-re-test measurements. The 8 heart transplant patients were imaged prior to their routine heart biopsies, and then the myocardial biopsy tissue was measure and compared to the pre-biopsy images.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Compare magnetic resonance imaging measurements of triglyceride accumulation in myocardial tissue with ex vivo myocardial tissue collected from heart transplant patients who have had routine clinical heart biopsy.
| Arm | Type | Receives |
|---|---|---|
| Magnetic Resonance Spectroscopy | Experimental | Procedure: Magnetic Resonance SpectroscopyPatients will have Magnetic Resonance Spectroscopy to measure in vivo accumulation of triglycerides in myocardial tissue |
| Ex vivo heart biopsy | Experimental | Procedure: Ex vivo heart biopsyPatients will have their normal routine clinical heart biopsy of myocardial heart tissue. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- healthy volunteers
- heart transplant patients
- undergoing post transplant endomyocardial biopsy
- not experiencing significant rejection
- heart transplant patients must be 18-30 years old.
Key exclusion criteria (6 listed)
- <18 or >45
- pregnant
- significant systemic illness
- actively ill
- acute transplant rejection
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 |
|---|---|---|
| Magnetic Resonance SpectroscopyAlso: MRSMagnetic Resonance Spectroscopy is a noninvasive procedure that provides detailed body images on any plane. | Procedure or surgery | Magnetic Resonance Spectroscopy |
| Ex vivo heart biopsyAlso: heart biopsyHeart transplant patients will have their normal clinical routine heart biopsy | Procedure or surgery | Ex vivo heart biopsy |
Primary outcome
Correlation Co-efficient Between MRS Spectroscopy and Endomyocardial Biopsy in Heart Transplant Participants
Time frame: 2 to 10 days
Participants first had MRS spectroscopy then the MRS spectroscopy images were compared to endomyocardial biopsy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 430798Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8. doi: 10.1001/jama.241.19.2035.
- Background: PubMed 1516498Koskinen P, Manttari M, Manninen V, Huttunen JK, Heinonen OP, Frick MH. Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care. 1992 Jul;15(7):820-5. doi: 10.2337/diacare.15.7.820.
- Background: PubMed 2974889Abbott RD, Donahue RP, Kannel WB, Wilson PW. The impact of diabetes on survival following myocardial infarction in men vs women. The Framingham Study. JAMA. 1988 Dec 16;260(23):3456-60.
- Background: PubMed 4835750Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29-34. doi: 10.1016/0002-9149(74)90089-7. No abstract available.
- Background: PubMed 10677535Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1784-9. doi: 10.1073/pnas.97.4.1784.
- Individual participant dataSharing planned: Undecided
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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.
Robert Gropler, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magnetic Resonance Spectroscopy and Ex vivo heart biopsy in people with Heart Transplantation, run by Washington University School of Medicine 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 6 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 13 Sep 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Sep 2018). 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?
Correlation Co-efficient Between MRS Spectroscopy and Endomyocardial Biopsy in Heart Transplant Participants (time frame: 2 to 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00469911, which also lists 5 linked publications.
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 13 Sep 2018.