Clinical trial NCT04738838: Oxytocin on Cold Water Task Performance and Recovery
Official title: Evaluating Potential Benefits of Intranasal Oxytocin on Undersea Operator Training and Performance: Cold Water Task Performance and Recovery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cold Exposure
Lead sponsor: Florida Institute for Human and Machine Cognition
Sponsor class: OTHER
Collaborators: name: Office of Naval Research (ONR)
name: University of Florida
First posted: 2021-02-04
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, placebo-controlled, randomized crossover design
Primary purpose: PREVENTION

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* Recreationally skilled swimmers

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Cognitive performance assessment score change (code substitution)
timeFrame: Within 3 hours post-treatment
measure: Cognitive performance assessment score change (code substitution)
timeFrame: Within 3 hours post-treatment
measure: Cognitive performance assessment score change (reaction time)
timeFrame: Within 3 hours post-treatment
measure: Cognitive performance assessment score change (reaction time)
timeFrame: Within 3 hours post-treatment
measure: Oculometric assessment score change (saccades)
timeFrame: Within 3 hours post-treatment
measure: Oculometric assessment score change (blink rate)
timeFrame: Within 3 hours post-treatment
measure: Oculometric assessment score change (blink duration)
timeFrame: Within 3 hours post-treatment
Secondary outcomes:
measure: Reduced rating of perceived exertion (RPE) during physical assessment post-cold water exposure
timeFrame: Within 3 hours post-treatment
Other outcomes:
measure: Difference in grip strength in cold water
timeFrame: Within 3 hours post-treatment
measure: Difference in manual dexterity (underwater knot untying) in cold water
timeFrame: Within 3 hours post-treatment
measure: Difference in manual dexterity (underwater peg board assessment) in cold water
timeFrame: Within 3 hours post-treatment
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Pensacola
country: United States
facility: Florida Institute for Human and Machine Cognition
state: Florida
Study officials:
affiliation: Florida Institute for Human and Machine Cognition
name: Marcas Bamman, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: