Ignite Creation Date:
2024-05-06 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 1:55 PM
Study NCT ID:
NCT04732247
Status:
COMPLETED
Last Update Posted:
2024-02-22
First Post:
2021-01-06
Brief Title:
Oxytocin for Oxidative Stress and Inflammation
Sponsor:
Florida Institute for Human and Machine Cognition
Organization:
Florida Institute for Human and Machine Cognition
Study Overview
Official Title:
Evaluating Potential Benefits of Intranasal Oxytocin on Undersea Operator Training and Performance Hyperoxic Swim-Induced Oxidative Stress and Inflammation
Status:
COMPLETED
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 eg 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
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 eg 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
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 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 eg 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 N40 18-39 yo 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 11 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
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 eg 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 N40 18-39 yo 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 11 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None