T-Cell Mitochondrial Respiration Response to Ketone Monoester Supplement in Healthy Volunteers and COVID-19

Sponsor

Duke University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05798260

Collaborator

(none)

Enrollment

Location

4.1

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

T-Cell Mitochondrial Respiration Response to Ketone monoester (Ketoneaid) in Healthy Volunteers and COVID-19

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Acute Respiratory Distress Syndrome	Diagnostic Test: Agilent Seahorse XF Cell Mito Stress Test

Study Design

Study Type:

Observational

Anticipated Enrollment :

15 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Intensive Care Unit (ICU) Biospecimen and Data Repository

Actual Study Start Date :

Mar 27, 2023

Anticipated Primary Completion Date :

Jul 31, 2023

Anticipated Study Completion Date :

Jul 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Healthy Volunteers Healthy Volunteers	Diagnostic Test: Agilent 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 Other Names: Ketoneaid (Ketone monoester)
COVID-19 positive admitted to the ICU and on the ventilator COVID-19 positive admitted to the ICU and on the ventilator	Diagnostic Test: Agilent 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 Other Names: Ketoneaid (Ketone monoester)

Arm

Intervention/Treatment

Healthy Volunteers

Diagnostic Test: Agilent 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

Other Names:

Ketoneaid (Ketone monoester)

COVID-19 positive admitted to the ICU and on the ventilator

Diagnostic Test: Agilent Seahorse XF Cell Mito Stress Test

Other Names:

Ketoneaid (Ketone monoester)

Outcome Measures

Primary Outcome Measures

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
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.
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.
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.

Secondary Outcome Measures

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
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