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T-Cell Mitochondrial Respiration Response to Ketone monoester (Ketoneaid) in Healthy Volunteers and COVID-19
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Volunteers | Healthy Volunteers |
| |
| COVID-19 positive admitted to the ICU and on the ventilator | COVID-19 positive admitted to the ICU and on the ventilator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Agilent Seahorse XF Cell Mito Stress Test | Diagnostic Test | The Agilent Seahorse XF Cell Mito Stress Test measures key parameters of mitochondrial function by directly measuring the oxygen consumption rate (OCR) of cells on the Seahorse XFe and XF Extracellular Flux Analyzers. It is a plate-based live cell assay that allows to monitor spare respiratory capacity (SRC), basal respiration, ATP production-coupled respiration, maximal respiration, and non-mitochondrial respiration in real time before and after ketone monoester |
| Measure | Description | Time Frame |
|---|---|---|
| Spare Respiratory Capacity (SRC) | This measurement indicates the capability of the cell to respond to an energetic demand as well as how closely the cell is to respiring to its theoretical maximum. The cell's ability to respond to demand can be an indicator of cell fitness or flexibility | through study completion, an average of 2 months |
| Basal Respiration | Oxygen consumption used to meet cellular ATP demand resulting from mitochondrial proton leak. Shows energetic demand of the cell under baseline conditions. | through study completion, an average of 2 months |
| ATP production-coupled Respiration | The decrease in oxygen consumption rate upon injection of the ATP synthase inhibitor oligomycin represents the portion of basal respiration that was being used to drive ATP production. Shows ATP produced by the mitochondria that contributes to meeting the energetic needs of the cell. | upon admission |
| Maximal Respiration | The maximal oxygen consumption rate attained by adding the uncoupler FCCP. FCCP mimics a physiological "energy demand" by stimulating the respiratory chain to operate at maximum capacity, which causes rapid oxidation of substrates (sugars, fats, and amino acids) to meet this metabolic challenge. Shows the maximum rate of respiration that the cell can achieve. | upon admission |
| Non-Mitochondrial Respiration | Oxygen consumption that persists due to a subset of cellular enzymes that continue to consume oxygen after the addition of rotenone and antimycin A. This is important to get an accurate measure of mitochondrial respiration. | through study completion, an average of 2 months |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygen Consumption Rate (OCR) | The oxygen consumption rate (OCR) of cells is an important indicator of normal cellular function. It is used as a parameter to study mitochondrial function as well as a marker of factors triggering the switch from healthy oxidative phosphorylation to aerobic glycolysis | through study completion, an average of 2 months |
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Inclusion Criteria:
COVID-19 with ARDS and on the ventilator
Exclusion Criteria:
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Patients admitted at Duke Hospital Medical and Surgical ICU with COVID-19 manifested with ARDS and on the ventilator
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| Name | Affiliation | Role |
|---|---|---|
| Christina Barkauskas, MD | Research Director Duke Medical ICU | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Christina Barkauskas | Durham | North Carolina | 27710 | United States |
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| extracellular acidification rate (ECAR) | Measuring the extracellular acidification rate (ECAR) provides a method for detection of glycolytic flux in T-cells in response to ketone mono ester | through study completion, an average of 2 months |