Heart Transplant RejectionANTIPARTICLENCT05772442
Cardiac Transplant Metabolomics With and Without Rejection
An observational study of Heart Transplant Rejection, run by Western University, Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplant Rejection
- What is being tested?
- Extra blood samples (5-10 mL) drawn
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Jul 2024to Apr 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Patients or substitute decision makers declined to participate in this study.
Trial locations and contacts
No sites are listed yet.
Stuart Smith, MD contact
About this study
Official title: Investigating the Metabolomic Profile of Transplanted Heart With and Without Pathological Signs of Rejection
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.
Read the 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.
- Conditions
- Heart Transplant Rejection
- Being tested
- Extra blood samples (5-10 mL) drawn
- Keywords
- Transplant, Metabolomics, Rejection
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extra blood samples (5-10 mL) drawnDiagnostic test
Extra blood samples will be sent for metabolomics analysis.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Extra blood samples (5-10 mL) drawn |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1-2 year to obtain these samples.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2023
- Study startJul 2024 (estimated)
- Primary completionOct 2025 (estimated)
- Study completionApr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Heart Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Western University, CanadaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western University, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Cardiovascular Society, Bayer, University of Alberta, Queen's University
- Responsible party
- Sponsor
- Investigators
- Stuart Smith, MD, Principal investigator, Western University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05772442
- Sponsor's protocol ID
- 122451
- Acronym
- ANTIPARTICLE
- Status last verified
- Jul 2024
- First submitted
- 5 Mar 2023
- Last updated
- 23 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 26497799Almenar 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.
PubMed 16386612Cooper 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.
PubMed 17980265Zwang 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.
PubMed 24342957CHIBA 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.
PubMed 13878918Kolwicz 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.
PubMed 23948585Akki 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.
PubMed 18278440Lin 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.
PubMed 29133921Xiong 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.
PubMed 34978755Xiong 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.
PubMed 30740395
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Metabolomic Profile of Transplanted Heart With and Without Pathological Signs of Rejection
- ClinicalTrials.gov ID
- NCT05772442
- Acronym / sponsor ID
- ANTIPARTICLE / 122451
- Conditions
- Heart Transplant Rejection
- Keywords
- Transplant, Metabolomics, Rejection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Western University, CanadaUniversity, hospital or other
- Collaborators
- Canadian Cardiovascular Society, Bayer, University of Alberta, Queen's University
- Study start
- Jul 2024 (estimated)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Apr 2026 (estimated)
- First posted
- 16 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No pathological signs of rejection | – | Diagnostic Test: Extra blood samples (5-10 mL) drawnRoutine 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. |
| With pathological signs of rejection | – | Diagnostic Test: Extra blood samples (5-10 mL) drawnRoutine 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- Patients or substitute decision makers declined to participate in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extra blood samples (5-10 mL) drawnExtra blood samples will be sent for metabolomics analysis. | Diagnostic test | No pathological signs of rejection, With pathological signs of rejection |
Primary outcome
Metabolomics differences detected in the blood sample of patient with signs of transplant rejection vs. no rejection.
Time frame: 1-2 year to obtain these samples.
25 blood samples in the no rejection group and 25 blood samples in the rejection group will be collected.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Background: PubMed 26497799Andrew 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.
- Background: PubMed 16386612Almenar 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.
- Background: PubMed 17980265Cooper 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.
- Background: PubMed 24342957Zwang 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.
- Background: PubMed 13878918CHIBA 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.
- Background: PubMed 23948585Kolwicz 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.
- Background: PubMed 18278440Akki 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.
- Results publication: PubMed 29133921Lin 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.
- Results publication: PubMed 34978755Xiong 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.
- Results publication: PubMed 30740395Xiong 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.
- Individual participant dataSharing planned: Undecided
Related trials for Heart Transplant Rejection
Not yet recruiting
Molecular Evidence of Rejection Intervention Trial
Heart Transplant Rejection
Not yet recruiting
Superiority Assessment of Donor-derived Cell-FreE DNA ( Deoxyribonucleic Acid) for Cardiac Allograft REjection Monitoring
Heart Transplantation
Enrolling by invitationObservational study
Donor Derived Cell Free DNA (Dd-cfDNA) as a Biomarker for Allograft Rejection in Heart Transplant Recipients
Heart Transplantation
RecruitingObservational study
Magnetic Resonance Elastography as a Method to Estimate Stiffness of Soft Tissues
Heart Failure, Liver Fibrosis
RecruitingObservational study
Trifecta-Heart cfDNA-MMDx Study
Heart Transplant Rejection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart Smith, MD contact
Stuart Smith, MD principal investigator
Western University
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplant Rejection, run by Western University, Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ping Yu Xiong, MD, PhD (613-331-1718, PingYu.Xiong@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolomics differences detected in the blood sample of patient with signs of transplant rejection vs. no rejection. (time frame: 1-2 year to obtain these samples.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05772442, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2024.