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Abstract
Introduction Cardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial.
Study design The AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days.
Ethics and dissemination The institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings.
Trial registration number ClinicalTrials.gov: NCT02798276, pre-results.
- cardiac regeneration
- adipose progenitor cells
- chronic myocardial infarction
- tissue engineering
- pericardial adipose graft
- clinical trials
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Footnotes
Contributors All authors have read and approved submission of this manuscript. All have contributed in different ways to the final version of the manuscript.
Funding The AGTP II trial is an investigator initiated study, sponsored by the Germans Trias i Pujol Research Institute. It is supported by grants from Ministerio de Educación y Ciencia (SAF2014-59892-R), Ministerio de Economía y Competitividad (Juan de la Cierva, JCI-2012-14025), Fundació La MARATÓ de TV3 (201502, 201516) and Generalitat de Catalunya (SGR 2014 , CERCA Programme and PERIS Programme, Departament de Salut SLT002/16/00234, SLT002_16_00209). Additional funds will be provided by Red de Terapia Celular-TerCel (RD16/0011/0006) and CIBER Cardiovascular (CB16/11/00403), as part of the Plan Nacional de I+D+I, and cofunded by ISCIII-Sudirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), and “La Caixa” Banking Foundation. This work is developed within the AdvanceCat project with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian European Regional Development Fund (ERDF) operational programme 2014-2020.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The study was approved by the Germans Trias i Pujol Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The article is a rationale and design manuscript. Patients are being enrolled at the moment. No further data is available yet. In addition to the paper and the protocol, the informed consent documents are available from us and from the Germans Trias i Pujol Hospital Ethics Committee. PG, JL, CGM and ABG will have access to the final trial dataset.