Co-transplantation of Mesenchymal Stem Cell Derived Exosomes and Autologous Mitochondria for Patients Candidate for CABG Surgery With EF< 25% (Clinical Trial Phase ])
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- ejection fraction
Study Overview
Brief Summary
Heart failure (HF) and acute myocardial infarction that often follows are among the main causes of disability and death worldwide. As such, new treatments and biological drugs are needed to protect the heart against the harmful effects of ischemia and also reperfusion injury (IRI), preserve cardiac function, reduce the zone of myocardial infarction (MI), and improve patient outcomes. In this regard, it has been shown that mitochondrial dysfunction has a key role in the pathogenesis of heart ischemia, cardiomyopathy, and reperfusion injury. in this study which includes 4 groups of intervention, we try to minimize the damage by transplantation of mitochondria and administration of MSC-derived exosomes. MSC-derived exosomes limit inflammatory damage while fresh autologous exosomes limit oxidative stress.
Detailed Description
This research will be performed as a retrospective cohort study at Tehran Heart Center. Patients will be selected from CABG candidates with severely low Ejection fraction determined by speckle echocardiography. Patients with severe co-morbidities or cerebral damage will be excluded from the study. Detailed informed consent will be taken from the patients. Patients who refuse to provide consent will receive standard treatment.
Criteria
Inclusion Criteria:
- Patients who are a candidate for CABG due to CAD±MR
- History of Q-wave MI, less than one month
- Age: 35-80
- LVEF <=25% (by any imaging modality: echocardiography/SPECT/LV angiography and Cardiac MRI)
- Viability study as evidenced by low-dose dobutamine stress echocardiogram and/or thallium redistribution nuclear study (at least four viable segments).
Exclusion Criteria:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 35 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •• Patients who are candidate for CABG due to CAD±MR
- •History of Q-wave MI, less than one month
- •Age: 35-80
- •LVEF <=25% (by any imaging modality: echocardiography/SPECT/LV angiography and Cardiac MRI)
- •Viability study as evidenced by low-dose dobutamine stress echocardiogram and/or or thallium redistribution nuclear study (at least four viable segments).
Exclusion Criteria
- •Severe co-morbidities (e.g., renal failure, liver failure, etc.)
- •Inability to provide informed consent
- •Cerebral Damage
Arms & Interventions
exosome therapy
a) Intracoronary and intra-myocardial injection of exosomes (5 patients)
1 mL of exosomes containing 100 micrograms of exosomes
Intervention: mitochondria and MSC-derived exosomes (Biological)
mitochondria therapy
b) Intracoronary and intra-myocardial injection of mitochondria (5 patients)
1 mL of exosomes containing 10 million mitochondria
Intervention: mitochondria and MSC-derived exosomes (Biological)
co-transplantation of mitochondria and exosome therapy
c) co-transplantation Intracoronary and intra-myocardial injection of exosomes and mitochondria (5 patients)
1 mL of exosomes containing 100 micrograms of exosomes
1 mL of exosomes containing 10 million mitochondria
Intervention: mitochondria and MSC-derived exosomes (Biological)
placebo
1 mL of placebo solution
Intervention: mitochondria and MSC-derived exosomes (Biological)
Outcomes
Primary Outcomes
ejection fraction
Time Frame: 3 months
left ventricle ejection fraction
allergic reactions
Time Frame: 3 months
reactions including angioedema, hypotention, acute allergic reaction
Secondary Outcomes
- ECMO duration(duration after surgery if needed)
- NYHA(1 and 3 months post surgery)
- CMR(1 and 3 months post surgery)
- CK-MB(2 week)
- on pump duration(during the surgery)
- cTnT(2 week)
- SPECT(1 and 3 months post surgery)
Investigators
Ahmadi tafti
professor
Tehran University of Medical Sciences