Oxytocin on Cold Water Task Performance and Recovery

NCT ID: NCT04738838

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-20
• Study Completion Date: 2022-07-29

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.

Conditions

Cold Exposure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Oxytocin Nasal Spray

Single dose of intranasal oxytocin (48 IU) prior to testing protocol.

Group Type: EXPERIMENTAL

Oxytocin nasal spray

Intervention Type: DRUG

Intranasal treatment with oxytocin via nasal spray (48 IU per dose)

Placebo Nasal Spray

Single dose of intranasal treatment with placebo (identical to oxytocin nose spray minus the oxytocin)

Group Type: PLACEBO_COMPARATOR

Placebo nasal spray

Intervention Type: DRUG

Intranasal treatment with placebo via nasal spray

Interventions

Oxytocin nasal spray

Intranasal treatment with oxytocin via nasal spray (48 IU per dose)

Intervention Type: DRUG

Placebo nasal spray

Intranasal treatment with placebo via nasal spray

Intervention Type: DRUG

Other Intervention Names

Oxytocin; Placebo

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Office of Naval Research (ONR)

FED

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

Florida Institute for Human and Machine Cognition

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcas Bamman, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Florida Institute for Human and Machine Cognition

Locations

University of Florida

Gainesville, Florida, United States

Florida Institute for Human and Machine Cognition

Pensacola, Florida, United States

Countries

United States

Other Identifiers

IRB-2020-0002

Identifier Type: -

Identifier Source: org_study_id