Study on the Efficacy and Mechanism of Cardiac Rehabilitation for Stem Cell Mobilization and Heart Failure Improvement

Myocardial Infarction Clinical Trial

Official title:

An Association Study Between Cardiac Rehabilitation and Stem Cell Mobilization in Patients With Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00154466
• Other study ID #: 9261701248
• Status: Completed
• Phase: N/A
• First received: September 9, 2005
• Last updated: May 25, 2014
• Start date: July 2004
• Est. completion date: December 2011

Study information

• Verified date: May 2014
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

One emerging concept is that some form of injury or inflammation is a prerequisite for the success of circulating-cell participation in differentiated tissue structure and function. Once reperfusion is achieved in acute myocardial infarction, an intense inflammatory cascade is unleashed.

The architecture of the left ventricle rearranges, leading to ventricular remodeling. The "homing process"involves stem cell migration to the sites of injury or ischemia, which provides an environment that is favorable to growth and function. This microenvironment is a stimulus for homing and differentiation of stem cells of the appropriate lineage. It increases vascular permeability and expression of adhesion proteins like integrin, along with homing receptors that facilitate the attachment, which is mediated by cell-to-cell contact and chemoattractant release from local tissue injury.The migratory capacity of stem cells might be dependent on natural growth factors such as vascular endothelial growth factor (VEGF) , stromal cell-derived factor-1 (SDF-1)and stem cell factor (SCF).The expression of VEGF ,SDF-1 and SCF is highly up-regulated in hypoxic tissue, supporting the hypothesis that these factors may represent homing signals crucial to the recruitment of circulating progenitor cells to assist the endogenous repair mechanisms in the infarcted tissue. This study will examine whether cardiac rehabilitation increases the concentration of stem cell factors released into the bloodstream and if these factors are correlated with the improvement of heart function.

Description:

Exercise training has beneficial hemodynamic effects in patients with congestive heart failure.A similar benefit may be seen after MI, with an improvement in functional capacity averaging 20 percent. More important, however, is the possible effect on survival. In a meta-analysis of 24 trials examining the effect of cardiac rehabilitation after MI, there was a significant reduction in mortality with rehabilitation (odds ratio 0.81).

Previous studies focused on the effect of rehabilitation comes from the improvement of oxygen utilization in skeletal muscle. The effects on cardiac morphology and perfusion status were rather little to be addressed.

In this study, we will collect the questionaires, blood sampling for assay of stem cell factors, maximal O2 consumption, and cardiac MRI before and after cardiac rehabilitation.SDF-1 (stromal cell derived factor-1), SCF(stem cell factor), and VEGF (vasculoendothelial growth factor) will be measured by ELISA. Cardiac MRI will provide the information about (1) LV function, (2) scar size, and (3) perfusion status (dipyridamole stress MRI).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: December 2011
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria: myocardial infarction with CK more than 3000, status post revascularization therapy, clinical stable with regular follow-up at OPD, NYHA II-III -

Exclusion Criteria:sustained ventricular arrhythmia, hypertrophy cardiomyopathy, intolerance to exercise program

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Behavioral:
• cardiac rehabilitation
Those in the training group participated in a 3-month rehabilitation training program at an exercise intensity of 55% to 70% of peak oxygen uptake (VO2); those in the nontraining group continued their usual lifestyle.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (1)

Lee BC, Hsu HC, Tseng WY, Su MY, Chen SY, Wu YW, Chien KL, Chen MF. Effect of cardiac rehabilitation on angiogenic cytokines in postinfarction patients. Heart. 2009 Jun;95(12):1012-8. doi: 10.1136/hrt.2008.153510. Epub 2009 Mar 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial Blood Flow at Baseline and 3-month Follow-up	First-pass, contrast-enhanced myocardial perfusion images acquired for 80 heart beats in the left ventricle. Short-axis views were obtained after intravenous administration of gadodiamide. Perfusion studies were performed at rest and during the stress induced by a 4 min infusion of dipyridamole at a concentration of 0.14 mg/kg of body weight per minute.To determine absolute MBF values at rest and stress status, we adopted a model-independent deconvolution method proposed by Jerosch-Herold et al, a method that was previously validated in experimental animal studies by comparison with blood-flow measurements with radiolabelled microspheres.	3 months	Yes
Secondary	Angiogenic Cytokines at Baseline and 3-month Follow-up	Angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal-derived factor-1 (SDF-1) and stem cell factor (SCF) are known to increase the formation of new vessels at ischaemic sites and thus enhance myocardial perfusion. To rule out any effect of short-term exercise on cytokines levels, blood samples were always taken after at least 72 h of physical inactivity and overnight fasting when the subject had rested in the sitting position for at least 10 min. The plasma samples were immediately frozen and stored at -70°C. High-sensitivity ELISA (Bender MedSystems, R&D) were used to measure plasma levels of SCF, SDF-1 and VEGF according to the manufacturer's protocols.	3 months	Yes