MRS: Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00469911
• Collaborator: National Institutes of Health (NIH) (NIH), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 46
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Transplantation	Procedure: Magnetic Resonance Spectroscopy; Procedure: Ex vivo heart biopsy	N/A

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

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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)
• Primary Purpose: Diagnostic
• Official Title: Quantification of Intramyocardial Lipid by Proton Magnetic Resonance Spectroscopy
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Magnetic Resonance Spectroscopy Patients will have Magnetic Resonance Spectroscopy to measure in vivo accumulation of triglycerides in myocardial tissue	Procedure: Magnetic Resonance Spectroscopy; Magnetic Resonance Spectroscopy is a noninvasive procedure that provides detailed body images on any plane.; Other Names: MRS
Experimental: Ex vivo heart biopsy Patients will have their normal routine clinical heart biopsy of myocardial heart tissue.	Procedure: Ex vivo heart biopsy; Heart transplant patients will have their normal clinical routine heart biopsy; Other Names: heart biopsy

Outcome Measures

Primary Outcome Measures

1. Correlation Co-efficient Between MRS Spectroscopy and Endomyocardial Biopsy in Heart Transplant Participants [2 to 10 days]

   Participants first had MRS spectroscopy then the MRS spectroscopy images were compared to endomyocardial biopsy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University Medical School	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• National Institutes of Health (NIH)
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Robert Gropler, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Erratum in: JAMA 1989 Apr 7;261(13):1884.
• 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.
• Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8.
• Koskinen P, Mänttäri 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.
• 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.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00469911
• Other Study ID Numbers: 5P20RR02064302; 05-0759; P20RR020643
• First Posted: May 7, 2007
• Last Update Posted: Sep 13, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Washington University School of Medicine: Heart; Transplant; MRS; MRI; Spectroscopy

Study Results

Participant Flow

Arm/Group Title	Heart Transplant	Controls
Arm/Group Description	Compare Magnetic resonance myocardial lipid measurements with biopsy derived ex vivo measurements Magnetic Resonance Spectroscopy: It is basically the same as an MRI. It is a noninvasive procedure that provides detailed body images on any plane. Endocardial Biopsy: This is a standard of care procedure that is already performed on heart transplant patients. This is a procedure that takes a biopsy (tissue sample) of the heart muscle.	Normal volunteers used to assess reproducability of the MRS measurements
Period Title: Overall Study
STARTED	8	10
COMPLETED	8	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Heart Transplant	Control Subjects	Total
Arm/Group Description	Compare Magnetic resonance myocardial lipid measurements with biopsy derived ex vivo measurements Magnetic Resonance Spectroscopy: It is a noninvasive procedure that provides detailed body images on any plane. Endocardial Biopsy: This is a standard of care procedure that is already performed on heart transplant patients. This is a procedure that takes a biopsy (tissue sample) of the heart muscle.	Control subjects with a broad range of body mass indexes and physiological conditions.	Total of all reporting groups
Overall Participants	8	10	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	10 100%	18 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 62.5%	5 50%	10 55.6%
Male	3 37.5%	5 50%	8 44.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	8 100%	10 100%	18 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	8 100%	10 100%	18 100%
Region of Enrollment (Count of Participants)
United States	8 100%	10 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Correlation Co-efficient Between MRS Spectroscopy and Endomyocardial Biopsy in Heart Transplant Participants
Description	Participants first had MRS spectroscopy then the MRS spectroscopy images were compared to endomyocardial biopsy
Time Frame	2 to 10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Heart Transplant Patients
Arm/Group Description	Measurement of triglycerides in heart transplant patients using MRI
Measure Participants	8
Number [correlation co-efficient]	0.97

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Heart Transplant Patients
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	2 to 10 days
Arm/Group Title	Heart Transplant - Endomyocardial Biopsy		Control Subjects
Arm/Group Description	This is a procedure that takes a biopsy (tissue sample) of the heart muscle., and it was compared to the MRS Spectroscopy images		Normal volunteers used to assess reproducability of the MRS measurements
All Cause Mortality
	Heart Transplant - Endomyocardial Biopsy		Control Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Serious Adverse Events
	Heart Transplant - Endomyocardial Biopsy		Control Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Heart Transplant - Endomyocardial Biopsy		Control Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)

Limitations/Caveats

There were no limitations or caveats

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.