Clinical trial NCT00469911: Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy
Official title: Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Transplantation
Keywords: Heart
Transplant
MRS
MRI
Spectroscopy
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Center for Research Resources (NCRR)
First posted: 2007-05-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: DIAGNOSTIC

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* healthy volunteers
* heart transplant patients
* undergoing post transplant endomyocardial biopsy
* not experiencing significant rejection
* heart transplant patients must be 18-30 years old.

Exclusion Criteria:

* \<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)

Primary outcomes:
measure: Correlation Co-efficient Between MRS Spectroscopy and Endomyocardial Biopsy in Heart Transplant Participants
timeFrame: 2 to 10 days
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Robert Gropler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Koskinen 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.
citation: Abbott 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.
citation: Kannel 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.
citation: Zhou 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.