Cardiac Transplant Metabolomics With and Without Rejection

NCT05772442 | Not Yet Recruiting

• 1 other identifier: 122451
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Heart Transplant Rejection

Keywords

Transplant; Metabolomics; Rejection

Outcome Measures

Primary Outcomes (1)

• Metabolomics differences detected in the blood sample of patient with signs of transplant rejection vs. no rejection.

  25 blood samples in the no rejection group and 25 blood samples in the rejection group will be collected.

  1-2 year to obtain these samples.

Study Arms (2)

No pathological signs of rejection

Routine endomyocardial biopsy did no show pathological signs of rejection (0R) based on the International Society for Heart and Lung Transplantation (ISHLT) 2004 acute cellular rejection grading scheme.

Diagnostic Test: Extra blood samples (5-10 mL) drawn

With pathological signs of rejection

Routine endomyocardial biopsy showed pathological signs of rejection (1R, 2R, and 3R) based on the International Society for Heart and Lung Transplantation (ISHLT) 2004 acute cellular rejection grading scheme.

Diagnostic Test: Extra blood samples (5-10 mL) drawn

Interventions

Extra blood samples (5-10 mL) drawn DIAGNOSTIC_TEST

Extra blood samples will be sent for metabolomics analysis.

No pathological signs of rejection; With pathological signs of rejection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Western University, Canada: lead
• Canadian Cardiovascular Society: collaborator
• Bayer: collaborator
• University of Alberta: collaborator
• Queen's University: collaborator

Related Publications (10)

• Andrew J, Macdonald P. Latest developments in heart transplantation: a review. Clin Ther. 2015 Oct 1;37(10):2234-41. doi: 10.1016/j.clinthera.2015.08.019.

  PMID: 26497799 BACKGROUND

• Almenar L, Cardo ML, Martinez-Dolz L, Garcia-Palomar C, Rueda J, Zorio E, Arnau MA, Osa A, Palencia M. Risk factors affecting survival in heart transplant patients. Transplant Proc. 2005 Nov;37(9):4011-3. doi: 10.1016/j.transproceed.2005.09.160.

  PMID: 16386612 BACKGROUND

• Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R; American Heart Association; American College of Cardiology; European Society of Cardiology; Heart Failure Society of America; Heart Failure Association of the European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol. 2007 Nov 6;50(19):1914-31. doi: 10.1016/j.jacc.2007.09.008. No abstract available.

  PMID: 17980265 BACKGROUND

• Zwang NA, Turka LA. Transplantation immunology in 2013: New approaches to diagnosis of rejection. Nat Rev Nephrol. 2014 Feb;10(2):72-4. doi: 10.1038/nrneph.2013.262. Epub 2013 Dec 17.

  PMID: 24342957 BACKGROUND

• CHIBA C, WOLF PL, GUDBJARNASON S, CHRYSOHOU A, RAMOS H, PEARSON B, BING RJ. Studies on the transplanted heart. Its metabolism and histology. J Exp Med. 1962 Apr 1;115(4):853-66. doi: 10.1084/jem.115.4.853.

  PMID: 13878918 BACKGROUND

• Kolwicz SC Jr, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res. 2013 Aug 16;113(5):603-16. doi: 10.1161/CIRCRESAHA.113.302095.

  PMID: 23948585 BACKGROUND

• Akki A, Smith K, Seymour AM. Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation. Mol Cell Biochem. 2008 Apr;311(1-2):215-24. doi: 10.1007/s11010-008-9711-y. Epub 2008 Feb 16.

  PMID: 18278440 BACKGROUND

• Lin F, Ou Y, Huang CZ, Lin SZ, Ye YB. Metabolomics identifies metabolite biomarkers associated with acute rejection after heart transplantation in rats. Sci Rep. 2017 Nov 13;7(1):15422. doi: 10.1038/s41598-017-15761-3.

  PMID: 29133921 RESULT

• Xiong PY, Motamed M, Chen KH, Dasgupta A, Potus F, Tian L, Martin A, Mewburn J, Jones O, Thebaud A, Archer SL. Inhibiting pyruvate kinase muscle isoform 2 regresses group 2 pulmonary hypertension induced by supra-coronary aortic banding. Acta Physiol (Oxf). 2022 Feb;234(2):e13764. doi: 10.1111/apha.13764. Epub 2022 Jan 17.

  PMID: 34978755 RESULT

• Xiong PY, Tian L, Dunham-Snary KJ, Chen KH, Mewburn JD, Neuber-Hess M, Martin A, Dasgupta A, Potus F, Archer SL. Biventricular Increases in Mitochondrial Fission Mediator (MiD51) and Proglycolytic Pyruvate Kinase (PKM2) Isoform in Experimental Group 2 Pulmonary Hypertension-Novel Mitochondrial Abnormalities. Front Cardiovasc Med. 2019 Jan 25;5:195. doi: 10.3389/fcvm.2018.00195. eCollection 2018.

  PMID: 30740395 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Stuart Smith, MD

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ping Yu Xiong, MD, PhD

CONTACT

613-331-1718; PingYu.Xiong@lhsc.on.ca

Stuart Smith, MD

CONTACT

Stuart.Smith@lhsc.on.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2023
• First Posted: March 16, 2023
• Study Start: July 1, 2024
• Primary Completion: October 1, 2025
• Study Completion: April 1, 2026
• Last Updated: July 23, 2024

Record last verified: 2024-07