Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy

NCT ID: NCT00469911

Last Updated: 2018-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2009-06-30

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.

Conditions

Heart Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Magnetic Resonance Spectroscopy

Patients will have Magnetic Resonance Spectroscopy to measure in vivo accumulation of triglycerides in myocardial tissue

Group Type: EXPERIMENTAL

Magnetic Resonance Spectroscopy

Intervention Type: PROCEDURE

Magnetic Resonance Spectroscopy is a noninvasive procedure that provides detailed body images on any plane.

Ex vivo heart biopsy

Patients will have their normal routine clinical heart biopsy of myocardial heart tissue.

Group Type: EXPERIMENTAL

Ex vivo heart biopsy

Intervention Type: PROCEDURE

Heart transplant patients will have their normal clinical routine heart biopsy

Interventions

Magnetic Resonance Spectroscopy

Magnetic Resonance Spectroscopy is a noninvasive procedure that provides detailed body images on any plane.

Intervention Type: PROCEDURE

Ex vivo heart biopsy

Heart transplant patients will have their normal clinical routine heart biopsy

Intervention Type: PROCEDURE

Other Intervention Names

MRS; heart biopsy

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Gropler, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University Medical School

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 430798 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1516498 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2974889 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 4835750 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10677535 (View on PubMed)

Other Identifiers

05-0759

Identifier Type: OTHER

Identifier Source: secondary_id

P20RR020643

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5P20RR02064302

Identifier Type: -

Identifier Source: org_study_id