COVID-19 Acute Respiratory Distress Syndrome
Conditions
Keywords
mitochondria, ketone monoester, seahorse, ketoneaid, SRC, FCCP, ECAR
Brief summary
T-Cell Mitochondrial Respiration Response to Ketone monoester (Ketoneaid) in Healthy Volunteers and COVID-19
Interventions
DIAGNOSTIC_TESTAgilent Seahorse XF Cell Mito Stress 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
Sponsors
Duke University
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
COVID-19 with ARDS and on the ventilator
Exclusion criteria
* Pregnant * \<18 years * Steroid use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Basal Respiration | through study completion, an average of 2 months | Oxygen consumption used to meet cellular ATP demand resulting from mitochondrial proton leak. Shows energetic demand of the cell under baseline conditions. |
| Maximal Respiration | upon admission | 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. |
| Non-Mitochondrial Respiration | through study completion, an average of 2 months | 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. |
| Spare Respiratory Capacity (SRC) | through study completion, an average of 2 months | 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 |
| ATP production-coupled Respiration | upon admission | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| extracellular acidification rate (ECAR) | through study completion, an average of 2 months | Measuring the extracellular acidification rate (ECAR) provides a method for detection of glycolytic flux in T-cells in response to ketone mono ester |
| Oxygen Consumption Rate (OCR) | through study completion, an average of 2 months | 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 |
Countries
United States
Outcome results
None listed