Ignite Creation Date:
2024-05-06 @ 3:16 PM
Last Modification Date:
2024-10-26 @ 1:46 PM
Study NCT ID:
NCT04570384
Status:
COMPLETED
Last Update Posted:
2023-02-22
First Post:
2020-09-17
Brief Title:
Intravenous L-Citrulline Influence on the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19
Sponsor:
Asklepion Pharmaceuticals LLC
Organization:
Asklepion Pharmaceuticals LLC
Study Overview
Official Title:
Prospective Randomized Double-Blind Placebo-Controlled Phase II Trial of Intravenous L-Citrulline Turnobi to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 SARS-CoV-2 Illness
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Prospective Randomized Double-Blind Placebo-Controlled Phase II Trial of Intravenous L-Citrulline Turnobi to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients with COVID-19 SARS-CoV2 Illness To evaluate safety and efficacy of a bolus loading dose and continuous intravenous infusion of L-Citrulline compared to placebo in patients hospitalized with COVID-19 infection SARS-CoV-2
Detailed Description:
Intravenous L-citrulline Turnobi administration will safely restore the homeostasis of nitric oxide synthase by increasing both plasma citrulline and arginine levels Investigators also reason that restoration of citrullinearginine balance through citrulline administration will safely re-establish homeostasis of NOS lower oxidative stress and reduce inflammation thereby delaying and potentially preventing the need for invasive mechanical ventilation in participants hospitalized with COVID-19 infection SARS-CoV-2 The body lives in a delicate balance of homeostasis The ureaNO cycle plays a critical role in maintaining redox homeostasis and as such also plays a role in regulating inflammation The biochemical relationships are complex and depend on inter-organ transfer membrane transport and intracellular compartmentation However data above demonstrate that citrulline arginine and NO are critical in maintaining this homeostasis through their regulation of NOS Inflammation especially from infection results in decreased activity of CPS1 and increased activity of arginase which decreases levels of both citrulline and arginine These decreased levels result in dysregulated and uncoupled NOS which drives both overexuberant NO production and formation of ROS Both the NO production and ROS further exacerbate the inflammatory cascade resulting in other organ dysfunctions including acute lung injury Both inflammation and oxidative stress have been shown to be driving forces for the development of ALI and regulated NOS function is vital to reducing both Both plasma citrulline and arginine are deficient in sepsis and levels are inversely associated with development of ALI Furthermore citrulline replacement safely increases plasma levels of both citrulline and arginine in healthy volunteers BMT patients adults with sepsis children with sickle cell disease and children after congenital heart surgery It seems highly likely that citrulline therapy in the setting of COVID-19 SARS-CoV2 induced acute hypoxemic respiratory illness will safely increase citrulline and arginine levels and help re-establish NOS homeostasis resulting in NO production in compartments that are more homeostatically appropriate so as to reduce pulmonary vascular resistance and enhance coupling of NOS to minimize superoxide production thus reducing free radical mediated ALI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None