Tight Glycemic Control Increases Cardiac Stem Cells During Acute Myocardial Infarction - Full Text View

Purpose

Objectives. The investigators analysed the effects of tight glycemic control in regenerative potential of the myocardium during acute myocardial infarction (AMI).

Background. A strict glycemic control after AMI improves the cardiac outcome. The role of tight glycemic control in regenerative potential of the myocardium during acute myocardial ischemia are still largely unknown.

Methods. Sixty-five patients with first AMI undergoing coronary bypass surgery were studied: 25 normoglycemic patients served as control group; hyperglycemic patients (glucose >140 mg/dl) were randomized to intensive glycemic control (IGC, n=20; glucose goal 80-140 mg/dl) or conventional glycemic control (CGC, n=20; glucose goal180-200 mg/dl) for almost 3 days before surgery, using insulin infusion followed by subcutaneous insulin treatment. Echocardiographic parameters were investigated at admission and after treatment period. During surgery, oxidative stress (nitrotyrosine, O2- production), apoptosis (Caspase-3) and cardiac stem cells (CSCs) (c-kit, MDR1 and Sca-1 positive cells) were analysed in biopsy specimens taken from the peri-infarcted area.

Condition	Intervention	Phase
Myocardial Infarction Oxidative Stress Glycemic Control	Drug: Insulin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Tight Glycemic Control Increases Cardiac Stem Cells and Reduces Heart Remodeling During Acute Myocardial Infarction in Hyperglycemic Patients

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Heart Attack

Drug Information available for: Insulin human Dextrose

U.S. FDA Resources

Further study details as provided by Second University of Naples:

Primary Outcome Measures:

cardiac stem cells during acute myocardial infarction [ Time Frame: 3 days of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

heart remodeling during acute myocardial infarction [ Time Frame: 3 days of treatment ] [ Designated as safety issue: Yes ]

Enrollment:	65
Study Start Date:	January 2001
Study Completion Date:	January 2009
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: 1 25 normoglycemic patients as control group
Active Comparator: 2 20 hyperglycemic patients (glucose >140 mg/dl) randomized to conventional glycemic control by insulin (CGC group; glucose goal 180-200 mg/dl)	Drug: Insulin In the CGC group, continuous insulin infusion was started only when blood glucose levels exceeded 200 mg/dl and adjusted to keep blood glucose between 180 and 200 mg/dl. When blood glucose fell <180 mg/dl, insulin infusion was tapered slowed down and eventually stopped. In the IGC group, insulin infusion was started when blood glucose levels exceeded 140 mg/dl and adjusted to maintain glycemia at 80-140 mg/dl. After the start of insulin infusion protocol a glycemic control was provided every hour in order to obtain three consecutive values that were within the goal range. Plasma glucose levels were checked every two hours in both CGC and IGT patients throughout the study period. The infusion lasted until stable glycemic goal (ICG group: 80-140 mg/dl; CGC group: 180-200 mg/dl) at least for 24 h. Subcutaneous insulin was initiated at the cessation of the infusion. Insulin was given as short-acting insulin before meals and intermediate long-acting insulin in the evening, in both group.
Experimental: 3 20 hyperglycemic patients (glucose >140 mg/dl) were randomized to intensive glycemic control by insunin (IGC group; glucose goal 80-140 mg/dl)	Drug: Insulin In the CGC group, continuous insulin infusion was started only when blood glucose levels exceeded 200 mg/dl and adjusted to keep blood glucose between 180 and 200 mg/dl. When blood glucose fell <180 mg/dl, insulin infusion was tapered slowed down and eventually stopped. In the IGC group, insulin infusion was started when blood glucose levels exceeded 140 mg/dl and adjusted to maintain glycemia at 80-140 mg/dl. After the start of insulin infusion protocol a glycemic control was provided every hour in order to obtain three consecutive values that were within the goal range. Plasma glucose levels were checked every two hours in both CGC and IGT patients throughout the study period. The infusion lasted until stable glycemic goal (ICG group: 80-140 mg/dl; CGC group: 180-200 mg/dl) at least for 24 h. Subcutaneous insulin was initiated at the cessation of the infusion. Insulin was given as short-acting insulin before meals and intermediate long-acting insulin in the evening, in both group.

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Eligibility

Ages Eligible for Study:	40 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

evidence of AMI within the last 8 h (troponin-I >2.50 µg/l together with either typical symptoms of angina or electrographic criteria of ST-segment modification)
first uncomplicated AMI
the need for CABG

Exclusion Criteria:

previous AMI
inflammatory disorders
malignancy
renal diseases infections

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00863629

Locations

Italy
Second University of Naples
Naples, Italy, i-80131

Sponsors and Collaborators

Second University of Naples

Investigators

Principal Investigator:

Raffaele Marfella, MD, PhD

Second University of Naples

More Information

Publications:

Kunz GA, Liang G, Cuculi F, Gregg D, Vata KC, Shaw LK, Goldschmidt-Clermont PJ, Dong C, Taylor DA, Peterson ED. Circulating endothelial progenitor cells predict coronary artery disease severity. Am Heart J. 2006 Jul;152(1):190-5. Erratum in: Am Heart J. 2006 Oct;152(4):776. Cuculoski, Florim [corrected to Cuculi, Florim].

Assmus B, Walter DH, Lehmann R, Honold J, Martin H, Dimmeler S, Zeiher AM, Schächinger V. Intracoronary infusion of progenitor cells is not associated with aggravated restenosis development or atherosclerotic disease progression in patients with acute myocardial infarction. Eur Heart J. 2006 Dec;27(24):2989-95. Epub 2006 Oct 19.

Pal R. Embryonic stem (ES) cell-derived cardiomyocytes: A good candidate for cell therapy applications. Cell Biol Int. 2009 Mar;33(3):325-36. Epub 2008 Dec 14.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Marfella R, Sasso FC, Cacciapuoti F, Portoghese M, Rizzo MR, Siniscalchi M, Carbonara O, Ferraraccio F, Torella M, Petrella A, Balestrieri ML, Stiuso P, Nappi G, Paolisso G. Tight glycemic control may increase regenerative potential of myocardium during acute infarction. J Clin Endocrinol Metab. 2012 Mar;97(3):933-42. Epub 2011 Dec 14.

Responsible Party:	Raffaele Marfella, MD, PhD, Second University of Naples, Italy
ClinicalTrials.gov Identifier:	NCT00863629 History of Changes
Other Study ID Numbers:	I-4546789
Study First Received:	March 16, 2009
Last Updated:	March 17, 2009
Health Authority:	Italy: Ethics Committee

Keywords provided by Second University of Naples:

myocardial infarction
oxidative stress
stem cells
glycemic control

Additional relevant MeSH terms:

Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases

Cardiovascular Diseases
Vascular Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013