Pharmacologic Induction of Tolerance for Hypoxia & Hypothermia

NCT06129825 | Active Not Recruiting DMC

• 1 other identifier: HP-00108068
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypothermia; Hypoxia; Mountain Sickness

Outcome Measures

Primary Outcomes (1)

• Drug candidate effects on RBC energy metabolism

  The Investigator will specifically focus on relative glycolytic and pentose phosphate pathway flux, to determine robustness of RBC antioxidant capacity. Flux analysis will be performed by metabolomics (mass spectrometry).

  18-24months

Secondary Outcomes (1)

• Drug candidate effects on RBC resilience to oxidative stress.

  18-24months

Other Outcomes (3)

• Drug candidate effects on RBC deformability and aggregation.

  18-24months

• Drug candidate effects on RBC 02 affinity and Bohr effect.

  18-24months

• Drug candidate effects on RBC 02 vasoactivity.

  18-24months

Study Arms (1)

Healthy Adult Volunteers

Healthy Adults Volunteers \>/= 18yrs of age without acute or chronic illness.

Other: Prospective

Interventions

Prospective OTHER

Single arm, healthy adult volunteers for blood donation.

Healthy Adult Volunteers

Eligibility Criteria

• Age: 18 Years - 88 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Healthy Adults 18-88 years of age.

You may qualify if:

• Subject is \>/= 18years of age.
• Subject weighs a minimum of 110lbs
• Subject must be generally healthy individual

You may not qualify if:

• Suspected or diagnosed with ongoing (chronic) or acute infection
• Pregnant
• Non-English speaking
• Ages 89 and over

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• United States Department of Defense: collaborator

Study Sites (1)

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Fresh human blood.

MeSH Terms

Conditions

Hypothermia; Hypoxia; Altitude Sickness

Interventions

Longitudinal Studies

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cohort Studies; Epidemiologic Studies; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Allan Doctor, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: November 13, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (1)