Oxytocin for Oxidative Stress and Inflammation

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-01

Study Completion Date

2023-09-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Due to the pleiotropic effects of OT on whole body metabolism, thermogenesis, stress responses, pain, mood, inflammation, appetite, glycemic control, skeletal homeostasis, and skeletal muscle repair and regeneration, there is increasing interest in the administration of exogenous OT for benefits to human health, performance and resilience. However, the biological mechanisms by which OT exerts tissue-specific effects (e.g., skeletal muscle) remain poorly understood, particularly in humans. This project is designed to significantly advance this understanding while testing the central hypothesis that intranasally administered OT attenuates systemic and skeletal muscle oxidative stress and inflammation induced by the combined stressor of resistance swim exercise and hyperoxia.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Training Strategies to Maintain Performance

NCT07128511

Shortness of Breath Shortness of Breath/Dyspnea Respiratory Distress

NOT_YET_RECRUITING NA

Strategy to Avoid Excessive Oxygen for Critically Ill Trauma Patients

NCT04534959

Critical Illness Wounds and Injury Disease Attributes +1 more

ACTIVE_NOT_RECRUITING PHASE3

Flow veRsus OxygeNaTion In acutE ReSpiratory Failure

NCT03223948

Respiratory Failure

UNKNOWN NA

Physiology Regarding Apnoeic Oxygenation During Nasal Cannula Therapy at Different Flow Rates

NCT03478774

Apnoeic Oxygenation

COMPLETED NA

Incidence of Opioid-Induced Respiratory Depression in Medical and Trauma Patients

NCT03647696

Respiratory Depression Sedation

WITHDRAWN

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Naval Special Warfare (NSW) operators are exposed to a variety of extreme environmental conditions and intense physical demands. In addition to breathing high pressure and hyperoxic 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 these extreme conditions 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 including skeletal muscle and a number of peripheral targets. OT may attenuate acute cardiovascular stress responses, while chronic OT exposure may reduce risk of CVD and other chronic diseases via anti-inflammatory effects and attenuation of mitochondrial oxidative stress. These 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.

Due to the pleiotropic effects of OT on whole body metabolism, thermogenesis, stress responses, pain, mood, inflammation, appetite, glycemic control, skeletal homeostasis, and skeletal muscle repair and regeneration, there is increasing interest in the administration of exogenous OT for benefits to human health, performance and resilience. However, the biological mechanisms by which OT exerts tissue-specific effects (e.g., skeletal muscle) remain poorly understood, particularly in humans.

This project is designed to significantly advance this understanding while testing the central hypothesis that intranasally administered OT attenuates systemic and skeletal muscle oxidative stress and inflammation induced by the combined stressor of resistance swim exercise and hyperoxia. If efficacy is demonstrated, the ultimate deliverable would be an easily administered, adjunctive biological therapy expected to improve performance and resilience of undersea warfighters. The planned project will extend current IHMC research focused on developing biotechnologies to enhance human performance and resilience. The central hypothesis will be tested via two specific aims - using a rigorous, double-blind, placebo-controlled, randomized trial leveraging a wash-in design, enrolling N=40 18-39 y/o men.

Specific Aim 1. To investigate the efficacy of intranasal OT on attenuating systemic and skeletal muscle oxidative stress and inflammation induced by the combined stressor of intensive, resistance swim exercise and hyperoxia. Participants will be randomly assigned with a 1:1 distribution to 48 IU intranasal OT vs. placebo (saline). Investigators will test the effects of 4x per day (QID) intranasal treatment on performance and the acute inflammatory and oxidative stress responses to resistance swimming under hyperoxia, along with the timecourse of recovery over 48 h. To assess blood and muscle oxidative stress investigators will measure antioxidant enzymes, along with markers of oxidative stress-induced DNA damage, protein carbonylation, and lipid peroxidation. Systemic inflammation will be assessed via a 7-plex serum cytokine array, and muscle inflammation will be assessed via the TNF-a and IL-6 signaling pathways.

Specific Aim 2. To leverage proven molecular mapping strategies to identify key molecular transducers likely driving any effects of intranasal OT on systemic and muscle oxidative stress and inflammation throughout 48 h of recovery. Given the paucity of data on mechanisms by which exogenous OT exerts its effects, the investigators will take a discovery approach to identify novel molecular networks and pathways that are differentially regulated by OT vs. placebo during recovery from an intensive, resistance swim exercise under hyperoxia. To accomplish this the investigators will perform multi-level modeling that integrates data from metabolomics, transcriptomics (both long and small RNA sequencing from blood plasma and muscle), and miRNA sequencing of circulating extracellular vesicles (EVs).

If intranasal OT demonstrates efficacy, the deliverable would be an adjunctive biological therapy that mitigates oxidative stress as well as enhances performance during and recovery from resistance swimming under hyperoxia.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Oxidative Stress Inflammation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-blind, placebo-controlled, randomized trial leveraging a wash-in design

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

All will remain blinded until completion of human subjects data collection except the research pharmacist providing intranasal oxytocin or placebo.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Oxytocin nasal spray

4x per day (QID) intranasal treatment with oxytocin (48 IU per dose)

Group Type EXPERIMENTAL

Oxytocin nasal spray

Intervention Type DRUG

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

Placebo nasal spray

4x per day (QID) 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

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Oxytocin Placebo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Apparently healthy (assessed via health, activity, and medical history)
* BMI \< 30
* No chronic conditions that would preclude participation
* Recreationally skilled swimmer capable of a continuous 30 min kickboard swim

Exclusion Criteria

\- Regular smoking. The smoking exclusion includes all forms (cigarettes, vaping, etc) due to well-established effects on lung function and systemic oxidative stress and inflammation

Minimum Eligible Age

18 Years

Maximum Eligible Age

39 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes