Clinical trial NCT05772442: Cardiac Transplant Metabolomics With and Without Rejection
Official title: Investigating the Metabolomic Profile of Transplanted Heart With and Without Pathological Signs of Rejection
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Heart Transplant Rejection
Keywords: Transplant
Metabolomics
Rejection
Lead sponsor: Western University, Canada
Sponsor class: OTHER
Collaborators: name: Canadian Cardiovascular Society
name: Bayer
name: University of Alberta
name: Queen's University
First posted: 2023-03-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who had cardiac transplant undergoing routine blood work and endomyocardial biopsy in the catheterization lab at London Health Sciences Centre - University Hospital.

Brief summary: Patient who received a heart transplant may develop organ rejection. Currently, an invasive biopsy of the heart needs to be performed to diagnose rejection. The purpose of this research study is to identify novel metabolic biomarkers that can be developed into a blood test that can identify signs of rejection without doing a heart biopsy.

Detailed description: Background:

Cardiac transplantation remains the treatment of choice for end-stage heart failure. Rejection is a major risk factor affecting the outcome and survival in transplant recipients. Endomyocardial biopsy is the gold standard for diagnosis of post-transplantation rejection, but it is an invasive procedure with potential serious complications. Moreover, due to limited catheterization lab time and time required to process biopsied tissue, the transplanted organs could potentially receive irreversible damages upon diagnosis of acute rejection. Current available non-invasive test involving detecting donor DNA in recipient's blood is still costly and has many limitations. Hence, a better non-invasive and timely diagnostic approach with high sensitivity and specificity is needed to help improve the diagnosis of acute post-cardiac transplant rejection.

Methods At the London Health Science Centre, patient who had a cardiac transplant will undergo routine weekly blood sample collection and endomyocardial biopsy for the first 4 weeks to screen for acute rejection. After informed consent was obtained for routine endomyocardial biopsy and research study, endomyocardial tissue samples and blood will be collected from the patient. Two to three biopsy samples and the blood were processed according to the protocols provided by the Metabolomic Innovation Centre (Edmonton, Alberta, Canada). The sample will be analyzed using the high-performance chemical isotope labelling liquid chromatography mass spectrometry metabolomics platform.

Expected Results:

Using the non-targeted metabolomics, the primary objective is to identify promising novel candidate biomarkers from the blood samples that can help us identify patients who are in acute rejection post-cardiac transplant. The blood sample biomarkers can be validated with endomyocardial biopsy metabolomics data. In addition, characterizing the metabolic profile of transplanted heart can provide insights for the myocardial energetics in transplanted heart. These data can potentially help physicians predict the likelihood of patients developing rejection.

Conclusion:

Metabolomics is an emerging technology used for absolute quantification of metabolites in tissues, cells, and biological fluids based on mass spectrometry. Investigators are hoping to use this technology to identify novel candidate biomarkers that can be used to accurately predict the presence of acute rejection in post-cardiac transplant patients.

Eligibility criteria: Inclusion Criteria:

* All patients with heart transplant undergoing routine endomyocardial biopsy and blood work for transplant rejection screening and workup.
* Patients or substitute decision makers are able to provide informed consent to agree to participate in this study.

Exclusion Criteria:

* Patients or substitute decision makers declined to participate in this study.

Primary outcomes:
measure: Metabolomics differences detected in the blood sample of patient with signs of transplant rejection vs. no rejection.
timeFrame: 1-2 year to obtain these samples.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Western University
name: Stuart Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
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