Oxytocin for Oxidative Stress and Inflammation

NCT04732247 | Completed Phase 2 FDA Drug

• 1 other identifier: IRB-2020-0000
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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 (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.

Conditions

Oxidative Stress; Inflammation

Outcome Measures

Primary Outcomes (2)

• Change in muscle oxidative stress via glutathione reductase activity

  Change in muscle glutathione reductase enzyme activity assessed by measuring muscle tissue levels of the reduced product, glutathione (GSH)

  Change in muscle glutathione reductase activity from before to 3 hours after the resistance swim + hyperoxia

• Change in blood oxidative stress via glutathione reductase activity

  Change in blood glutathione reductase enzyme activity assessed by measuring blood levels of the reduced product, glutathione (GSH)

  Change in blood glutathione reductase activity from before to 3 hours after the resistance swim + hyperoxia

Secondary Outcomes (1)

• Change in systemic inflammation via serum concentration of interleukin-6 (IL-6)

  Change in serum IL-6 concentration from before to 3 hours after the resistance swim + hyperoxia

Other Outcomes (4)

• Change in muscle inflammation via muscle IL-6 pathway activity

  Change in muscle STAT3 phosphorylation from before to 24 hours after the resistance swim + hyperoxia

• Change in maximum aerobic power (VO2max)

  Change in VO2max from before to 24 hours after the resistance swim + hyperoxia

• Change in pulmonary function via spirometry

  Before and 1 hour after the resistance swim + hyperoxia

Study Arms (2)

Oxytocin nasal spray

EXPERIMENTAL

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

Drug: Oxytocin nasal spray

Placebo nasal spray

PLACEBO COMPARATOR

4x per day (QID) intranasal treatment with placebo (identical to oxytocin nose spray minus the oxytocin)

Drug: Placebo nasal spray

Interventions

Oxytocin nasal spray DRUG

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

Also known as: Oxytocin

Oxytocin nasal spray

Placebo nasal spray DRUG

Intranasal treatment with placebo via nasal spray

Also known as: Placebo

Placebo nasal spray

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

Sponsors & Collaborators

• Florida Institute for Human and Machine Cognition: lead
• Office of Naval Research (ONR): collaborator
• University of Florida: collaborator
• University of Alabama at Birmingham: collaborator
• Translational Genomics Research Institute: collaborator

Study Sites (3)

Translational Genomics Research Institute

Phoenix, Arizona, 85004, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Florida Institute for Human and Machine Cognition

Pensacola, Florida, 32502, United States

Location

MeSH Terms

Conditions

Inflammation

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Marcas M Bamman, PhD

  Florida Institute for Human & Machine Cognition

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All will remain blinded until completion of human subjects data collection except the research pharmacist providing intranasal oxytocin or placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: February 1, 2021
• Study Start: February 1, 2022
• Primary Completion: September 15, 2023
• Study Completion: September 15, 2023
• Last Updated: February 22, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)