- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04899635
POWER Myocardial Fatigue Study: a Biomechanical Assessment of Contractility of Human Myocardium (POWER)
Profiling Biomechanical Responses and Workload of the Human Myocardium to Explore the Concept of Myocardial Fatigue and Reversibility
Study Overview
Status
Intervention / Treatment
Detailed Description
A continuum of pathological states from fatigue, injury to damage of the myocardium has been proposed which complements the continuous spectrum of HF and reconciles the seemingly disparate plethora of mechanisms behind the pathophysiology of HF. Unlike skeletal muscle where mechanical stress can be readily removed upon fatigue, an impaired left ventricle continues to receive preload from the right ventricle and cannot rest, maintaining cardiac output only at the expense of increasing filling pressures (as in HF with preserved ejection fraction). If concurrently faced with high afterload from vascular stiffness, ventricular-arterial decoupling occurs, driving mechanical inefficiency and diminishing cardiac output (as in HF with reduced ejection fraction). Chances of recovery is linked to the degree of fatigue, cardiomyocyte loss and replacement with non-contractile fibrosis. Assuming that the myocardium is in a state of chronic fatigue before reaching advanced stages of fibrosis, cases such as aortic stenosis or hypertensive heart disease may potentially be reversible if the pathological load is promptly removed.
This study will be re-synthesizing existing knowledge of the biomechanical behaviour of healthy and diseased cardiac myocytes and muscle in a new light of the theoretical constructs of myocardial fatigue, aligned with the existing energy-starvation theory. It will be a proof-of-concept study. Just as Frank-Starling's relationship between preload and cardiac output emerged from pre-clinical studies on muscle behaviour with subsequently major clinical implications, this study represents a necessary stepping stone to adding a new layer of insight into the pathophysiology of heart failure (HF).
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Patrick Tran
- Email: patricktranphd@gmail.com
Study Contact Backup
- Name: Patrick Tran
- Phone Number: +442476965689
- Email: patrick.tran2@uhcw.nhs.uk
Study Locations
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Coventry, United Kingdom, CV22DX
- Recruiting
- University Hospitals Coventry and Warwickshire
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Contact:
- Ceri Jones
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Sub-Investigator:
- Patrick Tran
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Principal Investigator:
- Prithwish Banerjee
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Principal Investigator:
- Helen Maddock
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- All adult patients between 18 to 85-years old undergoing open-heart surgery who can undergo the consent process for the study
- Healthy donor hearts that are deemed non-transplantable and consent received from a legal representative
Exclusion Criteria:
This criterion is kept to a minimum since the availability of human myocardial samples is finite and dependent on the limited number of patients undergoing cardiac surgery annually within the local hospital.
- Patients who do not have the mental capacity to undergo the consent process
- For the safety of researchers, patients with evidence of ongoing blood-borne infections such as HIV, or a recent positive test for COVID-19 (within 10 days of last PCR test).
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Diseased cardiac tissue
Heart muscle or cells (cardiomyocytes) will be obtained from patients undergoing cardiac surgery, namely coronary artery bypass grafting or for severe valvular heart disease.
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Using contractility assays for muscle slices or the work-loop assay for isolated heart cells, the tissue preparation will undergo a series of contraction and relaxation under varying levels of preload, afterload, stimulation frequency and under other experimental conditions such as drug-induced inotropism.
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Healthy cardiac tissue
Healthy donor hearts from deceased individuals that are not transplantable due to technical reasons
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Using contractility assays for muscle slices or the work-loop assay for isolated heart cells, the tissue preparation will undergo a series of contraction and relaxation under varying levels of preload, afterload, stimulation frequency and under other experimental conditions such as drug-induced inotropism.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in the force generated by the muscle cell and/or muscle slice
Time Frame: Within a day for each experiment
|
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects
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Within a day for each experiment
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Changes in the velocity of shortening by the muscle cell and/or muscle slice
Time Frame: Within a day for each experiment
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This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects
|
Within a day for each experiment
|
Changes in the end-systolic force-length relationship of the muscle cell and/or muscle slice
Time Frame: Within a day for each experiment
|
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects, and calculated by integrating the above force and length changes.
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Within a day for each experiment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in the phosphorylation potential
Time Frame: Within a day for each experiment
|
This will be calculated by determining the above concentration of adenosine triphosphate and its metabolic by-product including inorganic phosphate, at different times of the contraction fatigue protocol (e.g.
before, during, and after).
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Within a day for each experiment
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Changes in the phosphocreatine/ATP ratio
Time Frame: Within a day for each experiment
|
This will be calculated by determining the above concentration of phosphocreatine and ATP at different times of the contraction fatigue protocol (e.g.
before, during and after).
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Within a day for each experiment
|
Collaborators and Investigators
Collaborators
Publications and helpful links
General Publications
- Tran P, Joshi M, Banerjee P. Concept of myocardial fatigue in reversible severe left ventricular systolic dysfunction from afterload mismatch: a case series. Eur Heart J Case Rep. 2021 Mar 7;5(3):ytab089. doi: 10.1093/ehjcr/ytab089. eCollection 2021 Mar.
- Banerjee P. Heart failure: a story of damage, fatigue and injury? Open Heart. 2017 Oct 15;4(2):e000684. doi: 10.1136/openhrt-2017-000684. eCollection 2017.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PB528721
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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