Tight Glycemic Control Increases Cardiac Stem Cells During Acute Myocardial Infarction

NCT00863629 | Completed Phase 4 DMC

• 1 other identifier: I-4546789
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myocardial Infarction; Oxidative Stress; Glycemic Control

Keywords

myocardial infarction; oxidative stress; stem cells; glycemic control

Outcome Measures

Primary Outcomes (1)

• cardiac stem cells during acute myocardial infarction

  3 days of treatment

Secondary Outcomes (1)

• heart remodeling during acute myocardial infarction

  3 days of treatment

Study Arms (3)

1

NO INTERVENTION

25 normoglycemic patients as control group

2

ACTIVE COMPARATOR

20 hyperglycemic patients (glucose \>140 mg/dl) randomized to conventional glycemic control by insulin (CGC group; glucose goal 180-200 mg/dl)

Drug: Insulin

3

EXPERIMENTAL

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

Interventions

Insulin DRUG

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.

2; 3

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• previous AMI
• inflammatory disorders
• malignancy
• renal diseases infections

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

Second University of Naples

Naples, i-80131, Italy

Location

Related Publications (4)

• 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. doi: 10.1016/j.ahj.2006.02.001.

  PMID: 16824855 BACKGROUND

• Assmus B, Walter DH, Lehmann R, Honold J, Martin H, Dimmeler S, Zeiher AM, Schachinger 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. doi: 10.1093/eurheartj/ehl235. Epub 2006 Oct 19.

  PMID: 17053006 BACKGROUND

• Pal R. Embryonic stem (ES) cell-derived cardiomyocytes: a good candidate for cell therapy applications. Cell Biol Int. 2009 Mar;33(3):325-36. doi: 10.1016/j.cellbi.2008.12.001. Epub 2008 Dec 14.

  PMID: 19121644 BACKGROUND

• 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. doi: 10.1210/jc.2011-2037. Epub 2011 Dec 14.

  PMID: 22170713 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Insulin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Raffaele Marfella, MD, PhD

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 16, 2009
• First Posted: March 18, 2009
• Study Start: January 1, 2001
• Primary Completion: June 1, 2008
• Study Completion: January 1, 2009
• Last Updated: March 18, 2009

Record last verified: 2009-03

Locations

IT (1)