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

NCT03509441 | Completed

• 1 other identifier: 31279
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiomyopathies; Insulin Resistance; Non-ischemic Cardiomyopathy; Cardiac Fibrosis; Diabetes

Keywords

South Asian; Insulin Resistance; Cardiac Fibrosis; MRI; Diabetes; Cardiomyopathy

Outcome Measures

Primary Outcomes (9)

• Identifying patients with high fibrosis levels using peripheral blood samples

  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.

  Blood samples drawn once at baseline visit

• Insulin Sensitivity measured by OGTT

  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.

  OGTT done at baseline/ first visit

• Insulin Sensitivity measured by Fasting Lipid Panel

  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.

  Lipid Panel done at baseline/ first visit

• Left ventricular volume

  Cardiac MRI/ CMR done to noninvasively image heart and determine volume of left ventricle

  CMR done at baseline visit

• Left ventricular mass

  Cardiac MRI/ CMR done to noninvasively image heart and determine mass of left ventricle

  CMR done at baseline visit

• Ejection fraction %

  Cardiac MRI/ CMR done to noninvasively image heart and determine ejection fraction

  CMR done at baseline visit

• Myocardial tagging for strain analysis

  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

  CMR done at baseline visit

• Assessing diffuse fibrosis via T1 mapping

  A CMR technique called T1 mapping will be performed to calculate level of extracellular volume (ECV), which helps with the quantification of diffuse fibrosis

  CMR done at baseline visit

• Assessing level of edema via T2 mapping

  A CMR technique called T1 mapping will be performed assess amount of edema in the heart

  CMR done at baseline visit

Secondary Outcomes (4)

• Collagen turnover assessment

  Blood drawn at baseline visit

• Endothelial Function

  15 minute procedure done at baseline visit

• Urine test for albumin levels

  One urine test done at baseline visit

• Urine test for creatinine levels

  One urine test done at baseline visit

Study Arms (2)

South Asians with Insulin Resistance

125 patients (anticipated)

South Asians without Insulin Resistance

125 patients (anticipated)

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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

You may qualify if:

• \- South Asian

You may not qualify if:

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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

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.

MeSH Terms

Conditions

Cardiomyopathies; Insulin Resistance; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Rajesh Dash, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Abha Khandelwal, MD

  Stanford University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst Prof-Med Ctr Line

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: April 26, 2018
• Study Start: January 15, 2015
• Primary Completion: September 11, 2019
• Study Completion: November 11, 2019
• Last Updated: March 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)