Viewing Study NCT06129825



Ignite Creation Date: 2024-05-06 @ 7:46 PM
Last Modification Date: 2024-10-26 @ 3:13 PM
Study NCT ID: NCT06129825
Status: NOT_YET_RECRUITING
Last Update Posted: 2024-01-19
First Post: 2023-10-18

Brief Title: Pharmacologic Induction of Tolerance for Hypoxia Hypothermia
Sponsor: University of Maryland Baltimore
Organization: University of Maryland Baltimore

Study Overview

Official Title: Pharmacologic Induction of Tolerance for Hypoxia Hypothermia
Status: NOT_YET_RECRUITING
Status Verified Date: 2024-01
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: PhITHy-Ho
Brief Summary: Warfighter Performance Optimization in Extreme Environments remains an area of important and intense investigation with the following goals 1 Optimize sustain and augment medical readiness and physiological psychological performance in extreme and hazardous military operational environments and 2 develop joint DoD countermeasures and guidance to sustain performance assess physiological status and reduce injury risk in extreme and hazardous operational environments Successful and safe outcomes in extreme and hazardous operational environments require that warfighters maintain optimum cognitive and exercise performance during physiologic stress Extreme environmental conditions encountered in such environments include warfighter exposure to hypoxia and hypothermia alone or in combination Both hypoxia and hypothermia undermine O2 delivery system homeostasis imposing dangerous constraints upon warfighter cognitive and exercise capacity

While red blood cells RBCs are commonly recognized as O2 transport agents their function as a key signaling and control node in O2 system delivery homeostasis is newly appreciated Through O2 content-responsive modulation of RBC energetics biomechanics O2 affinity and control of vasoactive effectors in plasma - RBCs coordinate stabilizing responses of the lung heart vascular tree and autonomic nervous system - in a fashion that maintains O2 delivery system homeostasis in the setting of either reduced O2 availability hypobaric hypoxia or increased O2 demand hypothermia Human RBCs demonstrate adaptive responses to exercise hypoxia and hypothermia - these changes are commonly appreciated as a key element enabling high altitude adaptation However under conditions of hypoxia and hypothermia without prior adaptation RBC performance is adversely impacted and limits the dynamic range of stress adaptation for O2 delivery homeostasis - therefore limiting warfighter exercise capacity and cognitive performance in extreme environments such as during acute mountain sickness
Detailed Description: The investigators strategy is to a repurpose approved drugs with potential for salutary effect upon RBC performance attributes that contribute to O2 delivery homeostasis during stress and b efficiently identify lead candidates through sequential evaluation in relevant and rigorous benchtop and in vivo models that include examination for gender-specific effects Our assay platforms are selected to characterize RBC physiology relevant to O2 delivery with focus upon RBC O2 affinity energetics biomechanics vascular interaction and control of regional blood flow The investigator will sample RBC suspensions serially 0 13h and quantify the RBC performance attributes across the range of modeled environmental extremes defining RBC performance constraint as 20 impairment in each attribute and determine pharmacologic rescue defined as 20 improvement in each attribute using mixed model RM-ANOVA as a function of gender The investigator will power analysis to 80 at a5 based on our published data with these assays and experience this requires 10-15 subjectsgroup Drug candidates with evidence of PhIT-HyHo potential will advance to in vivo screening prioritized by the number of RBC attributes rescued per drug Specific description of our approach to evaluate each RBC performance attribute follows

RBC performance attributes will be quantified under controlled conditions Temperature 28 - 37C pO2 50 - 100 Torr alone and in combination in our temperature-controlled thin film tonometer38 NB temperature simulates hypothermic body temperature a glycolytic flux b resilience to oxidative stress c deformability aggregation d O2 affinity and Bohr effect e vasoactivity

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
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