Cold ExposurePhase 2NCT04738838
Oxytocin on Cold Water Task Performance and Recovery
A Phase 2 study testing Oxytocin nasal spray in people with Cold Exposure, run by Florida Institute for Human and Machine Cognition at 2 sites in United States.
Trial summary
Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure gases at depth, prolonged cold water immersion and inadequate recovery from sustained physical exertion negatively impact individual and team… Read more about this study
- Who is it for?
- Ages 18 to 39 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cold Exposure
- What is being tested?
- Oxytocin nasal spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 May 2022to 29 Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 39 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Recreationally skilled swimmers
Who cannot join
- Smoking/vaping, a history of psychiatric disorders, safety requirements related to the oxytocin administration [hypersensitivity to oxytocin or vasopressin, history of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, or psychogenic polydipsia, on vasoconstrictors such as desmopressin, pseudoephedrine, or antidiuretic medication, or anti-inflammatory drugs, or muscle relaxants, low sodium and high osmolality levels, excessive smoking, excessive drinking, and significant nasal pathology.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32611
Florida Institute for Human and Machine Cognition
Pensacola, Florida, 32502
About this study
Official title: Evaluating Potential Benefits of Intranasal Oxytocin on Undersea Operator Training and Performance: Cold Water Task Performance and Recovery
Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure gases at depth, prolonged cold water immersion and inadequate recovery from sustained physical exertion negatively impact individual and team performance. Biotechnologies that could mitigate the effects of cold as well as support physical recovery represent a significant unmet need for the NSW operational community.
Oxytocin (OT) has a wide range of actions both locally in the brain and peripherally in the body including skeletal muscle. These peripheral effects can be mediated by classic ligand-receptor activation given the abundant expression of the oxytocin receptor in peripheral tissues, along with local expression of OT in peripheral tissues where it is likely to act in an autocrine manner. Exogenous OT via intranasal administration is FDA Investigational New Drug (IND)-approved and has been demonstrated as an easy and safe method to increase circulating OT concentrations that may augment actions on peripheral tissues.
Read the detailed description
Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure gases at depth, prolonged cold water immersion and inadequate recovery from sustained physical exertion negatively impact individual and team performance. Biotechnologies that could mitigate the effects of cold as well as support physical recovery represent a significant unmet need for the NSW operational community.
Oxytocin (OT) has a wide range of actions both locally in the brain and peripherally in the body including skeletal muscle. These peripheral effects can be mediated by classic ligand-receptor activation given the abundant expression of the oxytocin receptor in peripheral tissues, along with local expression of OT in peripheral tissues where it is likely to act in an autocrine manner. Exogenous OT via intranasal administration is FDA Investigational New Drug (IND)-approved and has been demonstrated as an easy and safe method to increase circulating OT concentrations that may augment actions on peripheral tissues.
Cold water operators undergo an extensive and unique set of physical, physiological, and psychological stressors during a mission. In-water transit may exceed 6 hours submerged in cold water, on rebreathers, and in a confined space. During this lengthy transit, operators must maintain vigilance over navigation, vehicle, and life support controls while exposed to the risks of mixed gas or oxygen rebreather diving, alongside hypothermia, dehydration, undernutrition, and other factors that can significantly degrade operator performance. Once the team has reached target, they must be at peak cognitive and physical readiness as they carry out their mission objective. When the mission objective is complete, the operators undertake the lengthy return trip back to their deployed base. Optimized operator cognitive and physical performance is essential throughout all phases of a cold water mission, and safe and tolerable approach to optimizing warfighter performance and resilience will be key for future cold water operations.
Given the potential thermogenic and recovery effects or intranasal OT, we hypothesize that prophylactic OT administration, compared to placebo, will mitigate deficits in mission-relevant performance during and after cold water exposure. For this project we will utilize the ONR Cold Water Performance Task Battery, which was designed based on results from a task analysis combined with input from the cold water operator community. The task battery has been validated for its ability to induce changes in core and peripheral body temperature, manual dexterity, cognitive performance, and physical performance following cold water exposure. Our hypothesis will be tested via one specific aim enrolling N=24 18-39 y/o men by using a rigorous, double-blind, placebo- controlled, within-subjects randomized cross-over trial comparing 48 IU OT vs placebo (saline) in cold water performance and recovery.
Specific Aim 1. To investigate the impact of intranasal OT on cold water task performance and recovery using the ONR Cold Water Performance Task Battery, which includes cold water exposure; cognitive performance testing via oculometric assessment and the Defense Automated Neurobehavioral Assessment (DANA); and physical performance testing via a simulated ruck, ladder climb, and manual dexterity testing.
- Conditions
- Cold Exposure
- Being tested
- Oxytocin nasal spray, Placebo nasal spray
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxytocin nasal sprayDrug
Also called Oxytocin
Intranasal treatment with oxytocin via nasal spray (48 IU per dose)
Placebo nasal sprayDrug
Also called Placebo
Intranasal treatment with placebo via nasal spray
| Study group | Role | What they receive |
|---|---|---|
| Oxytocin Nasal Spray | Experimental | Single dose of intranasal oxytocin (48 IU) prior to testing protocol. Receives: Drug: Oxytocin nasal spray |
| Placebo Nasal Spray | Placebo comparator | Single dose of intranasal treatment with placebo (identical to oxytocin nose spray minus the oxytocin) Receives: Drug: Placebo nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive performance assessment score change (code substitution)
Changes in code substitution scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in milliseconds for response time.
Measured: Within 3 hours post-treatment
Cognitive performance assessment score change (code substitution)
Changes in code substitution scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in number of correct or incorrect responses.
Measured: Within 3 hours post-treatment
Cognitive performance assessment score change (reaction time)
Changes in choice reaction time scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in milliseconds for response time.
Measured: Within 3 hours post-treatment
Cognitive performance assessment score change (reaction time)
Changes in choice reaction time scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in number of correct or incorrect responses.
Measured: Within 3 hours post-treatment
Oculometric assessment score change (saccades)
Altered ocular response as measured by the I-Portal Portable Assessment System (i-PAS). Saccades will be monitored and counted throughout the duration of the assessment.
Measured: Within 3 hours post-treatment
Oculometric assessment score change (blink rate)
Altered ocular response as measured by the I-Portal Portable Assessment System (i-PAS). Number of blinks will be counted through the course of the assessment.
Measured: Within 3 hours post-treatment
Oculometric assessment score change (blink duration)
Altered ocular response in blink duration as measured by the I-Portal Portable Assessment System (i-PAS). Blink duration will be measured in milliseconds.
Measured: Within 3 hours post-treatment
Secondary outcomes (1)
Reduced rating of perceived exertion (RPE) during physical assessment post-cold water exposure
Participants will signal on the Borg (6-20) scale for whole body and lower body exertion following their exposure to cold water. Lower on the scale signal a lower level of perceived physical exertion.
Measured: Within 3 hours post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start20 May 2022
- Primary completion29 Jul 2022
- Study completion29 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cold ExposureStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, placebo-controlled, randomized crossover design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Florida Institute for Human and Machine Cognition
- Sponsor type
- University, hospital or other
- Collaborators
- Office of Naval Research (ONR), University of Florida
- Responsible party
- Sponsor
- Investigators
- Marcas Bamman, Ph.D., Principal investigator, Florida Institute for Human and Machine Cognition
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04738838
- Sponsor's protocol ID
- IRB-2020-0002
- Status last verified
- Mar 2026
- First submitted
- 6 Jan 2021
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Potential Benefits of Intranasal Oxytocin on Undersea Operator Training and Performance: Cold Water Task Performance and Recovery
- ClinicalTrials.gov ID
- NCT04738838
- Acronym / sponsor ID
- IRB-2020-0002
- Conditions
- Cold Exposure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Florida Institute for Human and Machine CognitionUniversity, hospital or other
- Collaborators
- Office of Naval Research (ONR), University of Florida
- Study start
- 20 May 2022 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 29 Jul 2022 (actual)
- First posted
- 4 Feb 2021 (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.
Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure gases at depth, prolonged cold water immersion and inadequate recovery from sustained physical exertion negatively impact individual and team performance. Biotechnologies that could mitigate the effects of cold as well as support physical recovery represent a significant unmet need for the NSW operational community.
Oxytocin (OT) has a wide range of actions both locally in the brain and peripherally in the body including skeletal muscle. These peripheral effects can be mediated by classic ligand-receptor activation given the abundant expression of the oxytocin receptor in peripheral tissues, along with local expression of OT in peripheral tissues where it is likely to act in an autocrine manner. Exogenous OT via intranasal administration is FDA Investigational New Drug (IND)-approved and has been demonstrated as an easy and safe method to increase circulating OT concentrations that may augment actions on peripheral tissues.
Detailed description
Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure gases at depth, prolonged cold water immersion and inadequate recovery from sustained physical exertion negatively impact individual and team performance. Biotechnologies that could mitigate the effects of cold as well as support physical recovery represent a significant unmet need for the NSW operational community.
Oxytocin (OT) has a wide range of actions both locally in the brain and peripherally in the body including skeletal muscle. These peripheral effects can be mediated by classic ligand-receptor activation given the abundant expression of the oxytocin receptor in peripheral tissues, along with local expression of OT in peripheral tissues where it is likely to act in an autocrine manner. Exogenous OT via intranasal administration is FDA Investigational New Drug (IND)-approved and has been demonstrated as an easy and safe method to increase circulating OT concentrations that may augment actions on peripheral tissues.
Cold water operators undergo an extensive and unique set of physical, physiological, and psychological stressors during a mission. In-water transit may exceed 6 hours submerged in cold water, on rebreathers, and in a confined space. During this lengthy transit, operators must maintain vigilance over navigation, vehicle, and life support controls while exposed to the risks of mixed gas or oxygen rebreather diving, alongside hypothermia, dehydration, undernutrition, and other factors that can significantly degrade operator performance. Once the team has reached target, they must be at peak cognitive and physical readiness as they carry out their mission objective. When the mission objective is complete, the operators undertake the lengthy return trip back to their deployed base. Optimized operator cognitive and physical performance is essential throughout all phases of a cold water mission, and safe and tolerable approach to optimizing warfighter performance and resilience will be key for future cold water operations.
Given the potential thermogenic and recovery effects or intranasal OT, we hypothesize that prophylactic OT administration, compared to placebo, will mitigate deficits in mission-relevant performance during and after cold water exposure. For this project we will utilize the ONR Cold Water Performance Task Battery, which was designed based on results from a task analysis combined with input from the cold water operator community. The task battery has been validated for its ability to induce changes in core and peripheral body temperature, manual dexterity, cognitive performance, and physical performance following cold water exposure. Our hypothesis will be tested via one specific aim enrolling N=24 18-39 y/o men by using a rigorous, double-blind, placebo- controlled, within-subjects randomized cross-over trial comparing 48 IU OT vs placebo (saline) in cold water performance and recovery.
Specific Aim 1. To investigate the impact of intranasal OT on cold water task performance and recovery using the ONR Cold Water Performance Task Battery, which includes cold water exposure; cognitive performance testing via oculometric assessment and the Defense Automated Neurobehavioral Assessment (DANA); and physical performance testing via a simulated ruck, ladder climb, and manual dexterity testing.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, placebo-controlled, randomized crossover design
| Arm | Type | Receives |
|---|---|---|
| Oxytocin Nasal Spray | Experimental | Drug: Oxytocin nasal spraySingle dose of intranasal oxytocin (48 IU) prior to testing protocol. |
| Placebo Nasal Spray | Placebo comparator | Drug: Placebo nasal spraySingle dose of intranasal treatment with placebo (identical to oxytocin nose spray minus the oxytocin) |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Recreationally skilled swimmers
Key exclusion criteria (1 listed)
- Smoking/vaping, a history of psychiatric disorders, safety requirements related to the oxytocin administration [hypersensitivity to oxytocin or vasopressin, history of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, or psychogenic polydipsia, on vasoconstrictors such as desmopressin, pseudoephedrine, or antidiuretic medication, or anti-inflammatory drugs, or muscle relaxants, low sodium and high osmolality levels, excessive smoking, excessive drinking, and significant nasal pathology.
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 |
|---|---|---|
| Oxytocin nasal sprayAlso: OxytocinIntranasal treatment with oxytocin via nasal spray (48 IU per dose) | Drug | Oxytocin Nasal Spray |
| Placebo nasal sprayAlso: PlaceboIntranasal treatment with placebo via nasal spray | Drug | Placebo Nasal Spray |
Primary outcome
Cognitive performance assessment score change (code substitution)
Time frame: Within 3 hours post-treatment
Changes in code substitution scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in milliseconds for response time.
Cognitive performance assessment score change (code substitution)
Time frame: Within 3 hours post-treatment
Changes in code substitution scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in number of correct or incorrect responses.
Cognitive performance assessment score change (reaction time)
Time frame: Within 3 hours post-treatment
Changes in choice reaction time scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in milliseconds for response time.
Cognitive performance assessment score change (reaction time)
Time frame: Within 3 hours post-treatment
Changes in choice reaction time scores as measured by the Defense Automated Neurobehavioral Assessment (DANA). Data will be measured in number of correct or incorrect responses.
Oculometric assessment score change (saccades)
Time frame: Within 3 hours post-treatment
Altered ocular response as measured by the I-Portal Portable Assessment System (i-PAS). Saccades will be monitored and counted throughout the duration of the assessment.
Oculometric assessment score change (blink rate)
Time frame: Within 3 hours post-treatment
Altered ocular response as measured by the I-Portal Portable Assessment System (i-PAS). Number of blinks will be counted through the course of the assessment.
Oculometric assessment score change (blink duration)
Time frame: Within 3 hours post-treatment
Altered ocular response in blink duration as measured by the I-Portal Portable Assessment System (i-PAS). Blink duration will be measured in milliseconds.
1 secondary outcome
Reduced rating of perceived exertion (RPE) during physical assessment post-cold water exposure
Time frame: Within 3 hours post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Marcas Bamman, Ph.D. principal investigator
Florida Institute for Human and Machine Cognition
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxytocin nasal spray in people with Cold Exposure, run by Florida Institute for Human and Machine Cognition at 2 sites 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 1 inclusion and 1 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: finished, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cognitive performance assessment score change (code substitution) (time frame: Within 3 hours post-treatment). The study lists 7 primary outcomes in all. 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 3 Apr 2026.