HypothermiaPhITHy-HoNCT06129825
Pharmacologic Induction of Tolerance for Hypoxia & Hypothermia
An observational study of Hypothermia and Hypoxia, run by University of Maryland, Baltimore at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 88 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypothermia, Hypoxia, Mountain Sickness
- What is being tested?
- Prospective
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2023to 30 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 88 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy Adults 18-88 years of age.
Who may be able to join
- Subject is >/= 18years of age.
- Subject weighs a minimum of 110lbs
- Subject must be generally healthy individual
Who cannot join
- Suspected or diagnosed with ongoing (chronic) or acute infection
- Pregnant
- Non-English speaking
- Ages 89 and over
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Baltimore
Baltimore, Maryland, 21201
About this study
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.
Read the detailed description
The investigator's 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, 1,3h) 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 a<5%; based on our published data with these assays and experience, this requires 10-15 subjects/group. 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 - 37°C; 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.
- Conditions
- Hypothermia, Hypoxia, Mountain Sickness
- Being tested
- Prospective
- Medical subject headings
- Hypothermia, Hypoxia, Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProspectiveOther
Single arm, healthy adult volunteers for blood donation.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Adult Volunteers | Healthy Adults Volunteers >/= 18yrs of age without acute or chronic illness. Receives: Other: Prospective |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 18-24months
Secondary outcomes (1)
Drug candidate effects on RBC resilience to oxidative stress.
The Investigator will assess robustness of RBC antioxidant systems following in vitro incubation in an oxidative environment. Outcome measures will include the ability of RBC's to scavenge oxidants including superoxide and hydrogen peroxide, RBC lysis and oxidative changes in RBC membrane proteins.
Measured: 18-24months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start11 Dec 2023
- Primary completion1 Dec 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypothermiaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Allan Doctor, MD, University of Maryland, Baltimore
- Investigators
- Allan Doctor, PhD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06129825
- Sponsor's protocol ID
- HP-00108068
- Acronym
- PhITHy-Ho
- Status last verified
- Feb 2026
- First submitted
- 18 Oct 2023
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacologic Induction of Tolerance for Hypoxia & Hypothermia
- ClinicalTrials.gov ID
- NCT06129825
- Acronym / sponsor ID
- PhITHy-Ho / HP-00108068
- Conditions
- Hypothermia, Hypoxia, Mountain Sickness
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 11 Dec 2023 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 13 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 investigator's 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, 1,3h) 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 a<5%; based on our published data with these assays and experience, this requires 10-15 subjects/group. 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 - 37°C; 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy Adult Volunteers | – | Other: ProspectiveHealthy Adults Volunteers >/= 18yrs of age without acute or chronic illness. |
Who may qualify
- Ages
- 18 to 88 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy Adults 18-88 years of age.
Key inclusion criteria (3 listed)
- Subject is >/= 18years of age.
- Subject weighs a minimum of 110lbs
- Subject must be generally healthy individual
Key exclusion criteria (4 listed)
- Suspected or diagnosed with ongoing (chronic) or acute infection
- Pregnant
- Non-English speaking
- Ages 89 and over
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProspectiveSingle arm, healthy adult volunteers for blood donation. | Other | Healthy Adult Volunteers |
Primary outcome
Drug candidate effects on RBC energy metabolism
Time frame: 18-24months
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).
1 secondary outcome
Drug candidate effects on RBC resilience to oxidative stress.
Time frame: 18-24months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Hypothermia
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
Not yet recruiting
Hypothermic Oxygenated Machine PErfusion During Ex-vivo SPLITting in Liver Pediatric Transplantation (HOPESPLIT)
Pediatric Liver Transplantation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan Doctor, PhD principal investigator
University of Maryland, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypothermia and Hypoxia, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug candidate effects on RBC energy metabolism (time frame: 18-24months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.