Clinical trial NCT00289822: Cell Therapy for Coronary Heart Disease
Official title: Cell Therapy for Coronary Heart Disease: Infusion of Autologous Ex Vivo Cultivated Endothelial Progenitor Cells (EPCs)" and Autologous Bone Marrow Progenitor Cells in Crossover Design for Improvement of Vascularization and Cardiac Function
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Coronary Artery Disease
Keywords: chronic heart failure
myocardial infarction
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2006-02-10
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Impaired contractile function after a heart attack and due to coronary heart disease is a major cause of "heart failure" limiting quality of life and prognosis, which cannot be prevented even with optimal standard therapy.

The aim of the current trial is to investigate whether infusion of progenitor cells into the coronary artery supplying the most dyskinetic left ventricular area may improve left ventricular contractile function, compared to no cell infusion in the control group, in patients with old (\>= 3 months) myocardial infarction.

Detailed description: * The study is an open-label, controlled, randomized single-center trial.
* Patients post myocardial infarction (\>= 3 months) with a patent infarct-related artery are included.
* Bone marrow-derived progenitor cells are aspirated under local anaesthesia, and after cell processing, are infused into the patent infarct-related artery during stop flow within the same day. Blood-derived progenitor cells are isolated out of 250ml peripheral venous blood, and after cell processing and 3 days culture, are infused into the patent infarct-related artery during stop flow. In addition, left ventricular angiography is performed. In the control group coronary angiography and left ventricular angiography without any intracoronary infusion are performed.
* After 3 months, left ventricular angiography is repeated, and patients of the control group cross-over to active treatment with progenitor cells, whereas patients initially treated with progenitor cells cross-over to the alternate cell type.
* The primary endpoint is the change in quantitative global left ventricular ejection fraction in LV angiography between the groups.

Eligibility criteria: Inclusion Criteria:

* Patients aged 18 to 80
* Patients post-myocardial infarction (\> 3 months old) or with diffuse ischemic CHD
* Signed informed consent

Exclusion Criteria:

- Existing neoplastic disease or signs of tumor recurrence within the last 5 years

* Active infection
* Active internal bleeding
* Stroke within the past 2 years
* Surgery or trauma within the past two months
* Uncontrolled hypertension over 160/100
* Arteriovenous malformations or aneurysms
* HIV infection
* Signs of significant kidney or liver failure (creatinine \> 2.0 mg/dL, GOT \> 2 x upper standard value)
* Thrombopenia (\< 100,000)
* Anemia (hemoglobin \< 8.5 g/dL)
* Mental retardation
* Participation in another clinical study
* Women of childbearing age
* Chronic inflammatory disease

Primary outcomes:
measure: Change in global left ventricular function (measured by quantitative left ventricular angiography)
Secondary outcomes:
measure: Quantitative parameters of regional left ventricular function of the target area
measure: changes in left ventricular volumes
measure: functional status as assessed by NYHA classification
measure: event-free survival after 4 months follow-up
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: J. W. Goethe University Hospitals
Study officials:
affiliation: J. W. Goethe University Hospitals
name: Andreas M Zeiher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J. W. Goethe University Hospitals
name: Volker Schaechinger, MD
role: STUDY_DIRECTOR
References:
citation: Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1222-32. doi: 10.1056/NEJMoa051779.
citation: De Rosa S, Seeger FH, Honold J, Fischer-Rasokat U, Lehmann R, Fichtlscherer S, Schachinger V, Dimmeler S, Zeiher AM, Assmus B. Procedural safety and predictors of acute outcome of intracoronary administration of progenitor cells in 775 consecutive procedures performed for acute myocardial infarction or chronic heart failure. Circ Cardiovasc Interv. 2013 Feb;6(1):44-51. doi: 10.1161/CIRCINTERVENTIONS.112.971705. Epub 2013 Jan 29.
citation: Leistner DM, Seeger FH, Fischer A, Roxe T, Klotsche J, Iekushi K, Seeger T, Assmus B, Honold J, Karakas M, Badenhoop K, Frantz S, Dimmeler S, Zeiher AM. Elevated levels of the mediator of catabolic bone remodeling RANKL in the bone marrow environment link chronic heart failure with osteoporosis. Circ Heart Fail. 2012 Nov;5(6):769-77. doi: 10.1161/CIRCHEARTFAILURE.111.966093. Epub 2012 Aug 30.