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Early MRI Detection of Myocardial Deterioration as a Preventive, Disease Staging, and Prognostic Biomarker in Insulin Resistance

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ClinicalTrials.gov Identifier: NCT03509441
Recruitment Status : Unknown
Verified April 2018 by Rajesh Dash, MD PHD, Stanford University.
Recruitment status was:  Recruiting
First Posted : April 26, 2018
Last Update Posted : April 26, 2018
Sponsor:
Information provided by (Responsible Party):
Rajesh Dash, MD PHD, Stanford University

Brief Summary:
The purpose of this study is to evaluate the relationship between insulin resistance (IR) and myocardial tissue abnormalities. The study will focus on a patient population, South Asians, with a high prevalence of IR.

Condition or disease
Cardiomyopathies Insulin Resistance Non-ischemic Cardiomyopathy Cardiac Fibrosis Diabetes

Detailed Description:
Cardiac fibrosis has been linked to adverse outcomes in non-ischemic cardiomyopathy. Fibrosis is also detectable in diabetic patients, but does not appear to closely track with insulin sensitivity. Hence, fibrosis may be an independent risk factor for adverse outcomes in IR and diabetic patients. As a result, a critical need exists to develop a non-invasive tool to identify and treat the highest-risk patients. Early detection of cardiac fibrosis and other CMR- detectable abnormalities in IR patients may help to 'stage' a patient's disease process and future risk of events, ultimately leading to an adjustment in the aggressiveness of their medical management and long-term monitoring accordingly. This project is aimed at reducing the mortality and morbidity associated with insulin resistance and diabetes, and the investigators believe this project could have a transformative impact on long-term diabetic care and shed new light upon the biology of diffuse cardiac fibrosis in insulin resistance and diabetes and its role in shaping the long-term cardiovascular risk for these patients.

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Early MRI Detection of Myocardial Deterioration as a Preventive, Disease Staging, and Prognostic Biomarker in Insulin Resistance
Actual Study Start Date : January 15, 2015
Estimated Primary Completion Date : November 11, 2019
Estimated Study Completion Date : November 11, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Group/Cohort
South Asians with Insulin Resistance
125 patients (anticipated)
South Asians without Insulin Resistance
125 patients (anticipated)



Primary Outcome Measures :
  1. Identifying patients with high fibrosis levels using peripheral blood samples [ Time Frame: Blood samples drawn once at baseline visit ]

    The investigators will collect and store peripheral blood samples from every patient, identify those with high and low fibrosis levels using our described protocol, and then select patients with disproportionately high fibrosis levels given their disease burden.

    The investigators can test for the level of fibrosis by generating induced pluripotent stem cell-derived cardiomyocytes (iPSC- CMs) from these collected blood samples. These iPSC-CMs will be tested, in vitro, for drug sensitivity, susceptibility to apoptotic stimuli, and the propensity to produce pro-fibrotic cytokine activation- all factors which will help the investigators determine fibrosis levels.


  2. Insulin Sensitivity measured by OGTT [ Time Frame: OGTT done at baseline/ first visit ]
    An oral glucose tolerance test with insulin measurement (OGTT) will be performed for all the patients. The investigators will draw blood to determine a fasting glucose measurement, and then the patients will be given a 75 g glucose solution to drink. Blood samples will be collected at serial time points (30 minutes, 60 minutes, 120 minutes) after ingestion of this liquid to determine blood glucose and insulin levels. The OGTT will help investigators determine the patient's degree of insulin sensitivity.

  3. Insulin Sensitivity measured by Fasting Lipid Panel [ Time Frame: Lipid Panel done at baseline/ first visit ]
    Baseline fasting lipids will be assessed to calculate a TG/HDL-C ratio, which also correlates with the degree of insulin sensitivity or lack thereof. These results will be correlated to the insulin sensitivity assessment performed by the OGTT.

  4. Left ventricular volume [ Time Frame: CMR done at baseline visit ]
    Cardiac MRI/ CMR done to noninvasively image heart and determine volume of left ventricle

  5. Left ventricular mass [ Time Frame: CMR done at baseline visit ]
    Cardiac MRI/ CMR done to noninvasively image heart and determine mass of left ventricle

  6. Ejection fraction % [ Time Frame: CMR done at baseline visit ]
    Cardiac MRI/ CMR done to noninvasively image heart and determine ejection fraction

  7. Myocardial tagging for strain analysis [ Time Frame: CMR done at baseline visit ]
    Cardiac MRI/ CMR done to noninvasively image heart and assess ventricular function through myocardial tagging. By modulating the magnetization gradient of the MRI prior to acquiring images, any parts of the heart which are not contracting can be identified. These images will be analyzed via strain analysis for such abnormalities in function

  8. Assessing diffuse fibrosis via T1 mapping [ Time Frame: CMR done at baseline visit ]
    A CMR technique called T1 mapping will be performed to calculate level of extracellular volume (ECV), which helps with the quantification of diffuse fibrosis

  9. Assessing level of edema via T2 mapping [ Time Frame: CMR done at baseline visit ]
    A CMR technique called T1 mapping will be performed assess amount of edema in the heart


Secondary Outcome Measures :
  1. Collagen turnover assessment [ Time Frame: Blood drawn at baseline visit ]
    Patients will have blood drawn for serum measurement of propeptides of several procollagens to determine the level of collagen turnover

  2. Endothelial Function [ Time Frame: 15 minute procedure done at baseline visit ]
    The investigators will also measure endothelial function using the endoPAT device, which employs noninvasive measurement of finger arterial pulsatile volume changes as a measure of endothelial function. This test takes approximately 15 minutes and is noninvasive.

  3. Urine test for albumin levels [ Time Frame: One urine test done at baseline visit ]
    24 Hour urine test for assessment of albumin levels

  4. Urine test for creatinine levels [ Time Frame: One urine test done at baseline visit ]
    24 Hour urine test for assessment of creatinine levels


Biospecimen Retention:   Samples With DNA
The investigators will probe individual patient risk based on initial cardiac fibrosis measurements. In insulin resistance, the degree of fibrosis may be out of proportion to disease severity, pointing to a genetic predisposition for increased cardiac cell dropout (i.e. apoptosis) and replacement fibrosis. To address this idea, the investigators will collect and store peripheral blood samples from every patient, identify those with high and low fibrosis levels, and then select patients with disproportionately high fibrosis levels given their disease burden. Induced pluripotent stem cell-derived cardiomyocytes (iPSC- CMs) will then be generated. The iPSC-CMs will be tested, in vitro, for drug sensitivity, susceptibility to apoptotic stimuli, and the propensity to produce pro-fibrotic cytokine activation. In this manner, the investigators will study the individual patient's myocardial cell features that increase the risk of cardiac fibrosis and the subsequent adverse outcomes that ensue.


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
South Asians between the age of 20 and 60 who have no active coronary heart disease or other non-ischemic cardiomyopathies
Criteria

Inclusion Criteria:

- South Asian

Exclusion Criteria:

  • Pregnant women
  • Patients with prior diagnoses of diabetes
  • Patients on insulin therapy
  • Patients with known coronary heart disease or other non-ischemic cardiomyopathies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03509441


Contacts
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Contact: Esha Roy, BS 408-313-7538 esharoy@stanford.edu
Contact: Rajesh Dash, MD, PhD 650-723-8138 rhombus@stanford.edu

Locations
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United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Krystal Solis    650-723-8138    krsolis@stanfordhealthcare.org   
Contact: Kathleen M Gallagher    (650) 723-8138    kgallagh@stanford.edu   
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Rajesh Dash, MD, PhD Stanford University
Study Director: Abha Khandelwal, MD Stanford University
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Responsible Party: Rajesh Dash, MD PHD, Asst Prof-Med Ctr Line, Stanford University
ClinicalTrials.gov Identifier: NCT03509441    
Other Study ID Numbers: 31279
First Posted: April 26, 2018    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rajesh Dash, MD PHD, Stanford University:
South Asian
Insulin Resistance
Cardiac Fibrosis
MRI
Diabetes
Cardiomyopathy
Additional relevant MeSH terms:
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Cardiomyopathies
Insulin Resistance
Fibrosis
Pathologic Processes
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Heart Diseases
Cardiovascular Diseases