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

October 30, 2009
February 3, 2014
February 2010
July 2014   (final data collection date for primary outcome measure)
To determine whether hyperglycemia alters myocardial perfusion in subjects with type 2 diabetes [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01021865 on ClinicalTrials.gov Archive Site
To determine whether GLP-1 modulates myocardial perfusion in subjects with type 2 diabetes. [ Time Frame: Nov 2009-2011 ] [ Designated as safety issue: No ]
Same as current
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Not Provided
 
Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes
Effects of Hyperglycemia on Myocardial Perfusion in Humans With and Without Type 2 Diabetes: Modulation by Glucagon-Like-Peptide-1

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.

Not Provided
Observational
Observational Model: Case Control
Time Perspective: Prospective
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Non-Probability Sample

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.

  • Coronary Artery Disease
  • Diabetes Mellitus Type 2
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
  • With type 2 Diabetes
    Intervention: Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere
  • Without type 2 diabetes
    Intervention: Drug: Glucagon-Like-Peptide-1/Regadenoson/Perflutren Lipid Microsphere
Abdelmoneim SS, Hagen ME, Mendrick E, Pattan V, Wong B, Norby B, Roberson T, Szydel T, Basu R, Basu A, Mulvagh SL. Acute hyperglycemia reduces myocardial blood flow reserve and the magnitude of reduction is associated with insulin resistance: a study in nondiabetic humans using contrast echocardiography. Heart Vessels. 2012 Nov 23. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
January 2015
July 2014   (final data collection date for primary outcome measure)

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.
Both
40 Years to 60 Years
Yes
Contact: Tamera M. Roberson, Res Coord 507-255-8621 roberson.tamera@mayo.edu
United States
 
NCT01021865
08-008750
Yes
Sharon Mulvagh, Mayo Clinic
Mayo Clinic
  • University of Nebraska
  • Astellas Pharma US, Inc.
  • Lantheus Medical Imaging
Principal Investigator: Ananda Basu, MBBS, M.D. Mayo Clinic
Principal Investigator: Sharon L Mulvagh, M.D. Mayo Clinic
Mayo Clinic
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP