NCT04500938

Brief Summary

Background: Treatment of heart failure has improved considerably in the past decades. Despite this improvement, the disease may progress into an end-stage ultimately leaving the physicians with no other treatment option than heart transplantation (HTx). There are multiple etiologies underlying heart failure. Cardiomyopathy is the leading cause for HTx in any age-group with coronary artery disease being the second most common cause in adult patients. Alterations in the mitochondrial function have been recognized as key factors in heart failure. During the transplant procedure the diseased heart is removed, providing a unique opportunity to collect samples eligible for thorough mitochondrial examination. Hopefully, the knowledge gained from this investigation will contribute with important insights in the diseased myocardial energy metabolism. Such knowledge may pave the way for development of treatments targeting both energy substrate supply for adenosine-triphosphate generation produced by the mitochondria as well as mitochondrial function in the failing heart. Hypothesis: The pathological myocardial function seen in heart failure is related to dysfunctional cardiac mitochondria Objective: To examine if cardiac mitochondrial function in end-stage heart failure of multiple etiologies is inferior to mitochondrial function in transplanted hearts with no signs of rejection or vasculopathy. Design: Myocardial mitochondrial function analyzed from 24 explanted hearts will be compared to endomyocardial biopsies from 20 HTx patients at scheduled biopsies (1 or 2 years after implantation).

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
24

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Aug 2020

Typical duration for all trials

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 22, 2020

Completed
15 days until next milestone

First Posted

Study publicly available on registry

August 6, 2020

Completed
24 days until next milestone

Study Start

First participant enrolled

August 30, 2020

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2024

Completed
Last Updated

August 6, 2020

Status Verified

August 1, 2020

Enrollment Period

3.5 years

First QC Date

July 22, 2020

Last Update Submit

August 3, 2020

Conditions

End-stage Heart Failure

Keywords

Mitochondrial functionHigh Resolution RespirometryHeart Transplantation

Outcome Measures

Primary Outcomes (5)

  • State 2 respiration (GM)

    Complex I-linked respiration, induced by Malate and Glutamate.

    Within 5 minutes.

  • State 3 respiration (GM3)

    Complex I-linked respiration with adenosine diphosphate (ADP), induced by Malate, Glutamate and ADP.

    Within 10 minutes.

  • State 3 respiration (GMS3)

    Complex I+II-linked respiration, induced by Malate, Glutamate, ADP and Succinate.

    Within 15 minutes.

  • State 4 respiration (4o)

    Complex I+II-linked respiration not linked to adenosine triphosphate production, induced by inhibition of complex V by Oligomycin.

    Within 30 minutes.

  • Residual Oxygen Consumption (ROX)

    Respiration not linked to the electron transport chain, induced by inhibition of complex I by Rotenone, complex III by Antimycin A and complex V by Oligomycin.

    Within 45 minutes.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

All heart transplanted patients, transplanted at Aarhus University Hospital, Denmark.

You may qualify if:

  • Informed consent from the recipient

You may not qualify if:

  • Myocardial biopsy from the explanted heart not feasible

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (6)

  • Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Goldfarb S, Levvey BJ, Meiser B, Rossano JW, Yusen RD, Stehlik J. The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant. 2015 Oct;34(10):1244-54. doi: 10.1016/j.healun.2015.08.003. Epub 2015 Aug 28. No abstract available.

    PMID: 26454738BACKGROUND

  • Murphy E, Ardehali H, Balaban RS, DiLisa F, Dorn GW 2nd, Kitsis RN, Otsu K, Ping P, Rizzuto R, Sack MN, Wallace D, Youle RJ; American Heart Association Council on Basic Cardiovascular Sciences, Council on Clinical Cardiology, and Council on Functional Genomics and Translational Biology. Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association. Circ Res. 2016 Jun 10;118(12):1960-91. doi: 10.1161/RES.0000000000000104. Epub 2016 Apr 28.

    PMID: 27126807BACKGROUND

  • Jespersen NR, Yokota T, Stottrup NB, Bergdahl A, Paelestik KB, Povlsen JA, Dela F, Botker HE. Pre-ischaemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischaemia-reperfusion. J Physiol. 2017 Jun 15;595(12):3765-3780. doi: 10.1113/JP273408. Epub 2017 Feb 27.

    PMID: 28093764BACKGROUND

  • Gormsen LC, Svart M, Thomsen HH, Sondergaard E, Vendelbo MH, Christensen N, Tolbod LP, Harms HJ, Nielsen R, Wiggers H, Jessen N, Hansen J, Botker HE, Moller N. Ketone Body Infusion With 3-Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study. J Am Heart Assoc. 2017 Feb 27;6(3):e005066. doi: 10.1161/JAHA.116.005066.

    PMID: 28242634BACKGROUND

  • Brown DA, Perry JB, Allen ME, Sabbah HN, Stauffer BL, Shaikh SR, Cleland JG, Colucci WS, Butler J, Voors AA, Anker SD, Pitt B, Pieske B, Filippatos G, Greene SJ, Gheorghiade M. Expert consensus document: Mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol. 2017 Apr;14(4):238-250. doi: 10.1038/nrcardio.2016.203. Epub 2016 Dec 22.

    PMID: 28004807BACKGROUND

  • Lund LH, Edwards LB, Kucheryavaya AY, Dipchand AI, Benden C, Christie JD, Dobbels F, Kirk R, Rahmel AO, Yusen RD, Stehlik J; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report--2013; focus theme: age. J Heart Lung Transplant. 2013 Oct;32(10):951-64. doi: 10.1016/j.healun.2013.08.006. No abstract available.

    PMID: 24054804BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Endomyocardial biopsies taken from the explanted heart after removal during heart transplantation.

Study Officials

  • Hans Eiskjær, MD, DMSc

    University of Aarhus

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Roni Nielsen, MD, PhD

CONTACT

51219363bent.niels@midt.rm.dk

Katrine Berg, PhD student

CONTACT

28897429katrbe@rm.dk

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 22, 2020

First Posted

August 6, 2020

Study Start

August 30, 2020

Primary Completion

February 28, 2024

Study Completion

February 28, 2024

Last Updated

August 6, 2020

Record last verified: 2020-08

Data Sharing

IPD Sharing
Will not share