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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00154466
First received: September 9, 2005
Last updated: May 25, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Myocardial Infarction
Behavioral: cardiac rehabilitation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Association Study Between Cardiac Rehabilitation and Stem Cell Mobilization in Patients With Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Myocardial Blood Flow at Baseline and 3-month Follow-up [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Angiogenic Cytokines at Baseline and 3-month Follow-up [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 58
Study Start Date: July 2004
Study Completion Date: December 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.
Other Name: exercise training
No Intervention: postinfarction patients
those in the nontraining group continued their usual lifestyle
Placebo Comparator: healthy controls
Age-, weight-, and height-matched subjects without cardiovascular risk factors were selected as healthy controls.

Detailed 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).

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

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  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00154466

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Bai-Chin Lee, MD National Taiwan University Hospital
Principal Investigator: Ssu-Yuan Chen, MD National Taiwan University Hospital
Principal Investigator: Wen-Yih Tseng, MD, PhD National Taiwan University Hospital
Study Director: Ming-Fong Chen, MD, PhD National Taiwan University Hospital
  More Information

Publications:
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00154466     History of Changes
Other Study ID Numbers: 9261701248
Study First Received: September 9, 2005
Results First Received: December 6, 2012
Last Updated: May 25, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Myocardial infarction, stem cell, cardiac rehabilitation

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 22, 2014