Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes (GLP-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Mayo Clinic
Sponsor:
Collaborators:
University of Nebraska
Astellas Pharma US, Inc.
Lantheus Medical Imaging
Information provided by (Responsible Party):
Sharon Mulvagh, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01021865
First received: October 30, 2009
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The overall goal of this proposal is to determine the effects of acute hyperglycemia and its modulation by Glucagon-like Peptide-1 (GLP-1) on myocardial perfusion in type 2 diabetes (DM). This study plan utilizes myocardial contrast echocardiography (MCE) to explore a) the effects of acute hyperglycemia on myocardial perfusion and coronary flow reserve in individuals with and without DM; and b) the effects of GLP-1 on myocardial perfusion and coronary flow reserve during euglycemia and hyperglycemia in DM. The investigators will recruit individuals with and without DM matched for age, gender and degree of obesity. The investigators will measure myocardial perfusion at rest and during vasodilator stress (to ascertain coronary flow reserve) while subjects are under controlled pancreatic clamp conditions during euglycemia (glucose ~100 mg/dl) and hyperglycemia (glucose ~250 mg/dl) in the presence and absence of concomitant GLP-1 infusion. The investigators believe that the translational significance of their studies is immense, impacting upon both acute and chronic cardiovascular disease manifestations. The effect of glycemic control on cardiovascular outcomes, morbidity and mortality remains an area of active investigation, fueled by the recent conflicting results of several large clinical trials (ACCORD, UKPDS, ADVANCE, VADT). If the investigators find that hyperglycemia is associated with altered myocardial perfusion, the mechanistic implications in the prevention and management of acute and chronic cardiovascular diseases in DM will be groundbreaking. Furthermore, if GLP-1 augments myocardial perfusion (as it does in the peripheral vasculature), the therapeutic benefits for prevention of cardiovascular events in this predisposed population are clear.


Condition Intervention
Coronary Artery Disease
Diabetes Mellitus Type 2
Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes: Modulation by Glucagon-Like-Peptide-1

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • To determine whether hyperglycemia alters myocardial perfusion in subjects with type 2 diabetes [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine whether GLP-1 modulates myocardial perfusion in subjects with type 2 diabetes. [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2010
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
With type 2 Diabetes Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere

GLP-1 at a rate of 1.2 pmol/kg/min

Regadenoson as a stress agent 0.4mg IV given during MCE

Definity:0.6 ml of Definity diluted with 30ml of 0.9% saline infused by SYRINGE Infusion Pump

Other Names:
  • Lexiscan
  • Definity
Without type 2 diabetes Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere

GLP-1 at a rate of 1.2 pmol/kg/min

Regadenoson as a stress agent 0.4mg IV given during MCE

Definity:0.6 ml of Definity diluted with 30ml of 0.9% saline infused by SYRINGE Infusion Pump

Other Names:
  • Lexiscan
  • Definity

  Eligibility

Ages Eligible for Study:   40 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

25 subjects with type 2 diabetes and 25non-diabetic subjects matched for age, gender and degree of obesity will be studied.

The diabetic subjects will be between 40 and 60 years of age and will have a body mass index of < or =35 kg/m2. Diabetic subjects treated according to ADA guidelines will be eligible for study including a blood pressure < 140/90, LDL cholesterol < 130 mg/dl, HDL cholesterol >40 mg/dl and triglycerides <200 mg/dl.

All nondiabetic subjects will not have a history of diabetes in their first degree family members. None of the subjects will have any overt evidence of cardiac, renal, pulmonary or hepatic disorder nor will they be engaging in regular vigorous physical activities. All subjects will undergo a resting ECG and a treadmill ECG test to ensure that they do not have active or occult coronary artery disease unless such testing had been completed within six months of enrollment and reported as normal.

Criteria

Inclusion Criteria:

  • Males and females
  • Age 40-60 years
  • BMI< or = 35 kg/m2
  • Diabetic subjects with HbA1c concentrations of < or = 8%.
  • Diabetic subjects will be either on diet and lifestyle therapy alone, or monotherapy with metformin or sulphonylureas (except glyburide).
  • All diabetic subjects should be on stable dose oral agent therapy for 3 months prior to enrollment.

Exclusion Criteria:

  • Subjects with cerebrovascular or peripheral vascular disease.
  • Subjects with suspected or overt autonomic neuropathy.
  • Diabetic subject on thiazolidinediones, insulin, GLP-1 based therapies (exenatide or sitagliptin), alpha-glucosidase inhibitors, glyburide or combination antidiabetic drug therapies.
  • Diabetics with microalbuminuria.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01021865

Contacts
Contact: Tamera M. Roberson, Res Coord 507-255-8621 roberson.tamera@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Tamera M Roberson    507-255-8621    roberson.tamera@mayo.edu   
Sub-Investigator: Sahar S Abdelmoneim Mohamed, M.B., B.Ch.         
Sub-Investigator: Rita Basu, M.D.         
Sub-Investigator: Debashis K Nandy, MBBS         
Sub-Investigator: Vishwanath Pattan, MBBS         
Sponsors and Collaborators
Mayo Clinic
University of Nebraska
Astellas Pharma US, Inc.
Lantheus Medical Imaging
Investigators
Principal Investigator: Ananda Basu, MBBS, M.D. Mayo Clinic
Principal Investigator: Sharon L Mulvagh, M.D. Mayo Clinic
  More Information

Publications:
Responsible Party: Sharon Mulvagh, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01021865     History of Changes
Other Study ID Numbers: 08-008750
Study First Received: October 30, 2009
Last Updated: February 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
GLP-1
Myocardial contrast echocardiography
Myocardial perfusion

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon
Glucagon-Like Peptide 1
Regadenoson
Perflutren
Definity
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins
Adenosine A2 Receptor Agonists
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents

ClinicalTrials.gov processed this record on September 22, 2014