Effects of Intramuscular (IM) Oxytocin on Pupil Diameter and Heart Rate Variability (HRV)

Study Overview
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Brief Summary
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The goal of this study is to test the effects of oxytocin on heart rate variability and pupil diameter, both of which have subtle effects on the activity rate of the autonomic nervous system.

Detailed Description
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This protocol focuses on two measures of autonomic control to quantify central actions of oxytocin. First, the study team proposes to examine the influence of oxytocin on heart rate variability with focus on its effect on high frequency variability, most commonly ascribed to parasympathetic nervous system activity acting to brake sympathetic tone. Intranasal oxytocin has been demonstrated to have a large effect size on this measure which can be repeated at frequent intervals. As a secondary assessment of parasympathetic activity, the study team will measure low frequency fluctuation in pupil diameter, termed hippus, which also reflects parasympathetic nervous system activity. This outcome measure can be assessed in 3 seconds using equipment currently being used under Institutional Review Board (IRB) approved protocols.

Official Title
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Effects of Intramuscular Oxytocin on Pupil Diameter and Heart Rate Variability

Conditions
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Chronic Pain Due to Injury

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female > 18 and < 66 years of age, Body Mass Index (BMI) <40 Generally in good health as determined by the Principal Investigator based on prior medical history Normal blood pressure and resting heart rate without medication Exclusion Criteria: Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin® Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk Women who are pregnant (positive result for serum pregnancy test at screening visit), Women who are currently nursing or lactating, women that have been pregnant within 2 years. Neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis. Previous eye surgery, eye medications, cataracts

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 66 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double blinded crossover treatment with oxytocin and placebo (saline)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin First, then Placebo<br>Subjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®), 10 International Units (IU) at the first visit. Then at the next visit, they will receive Intramuscular injection of (1 milliliter) saline. | Drug: Oxytocin<br>* Oxytocin 10 IU<br>* Other names: Pitocin;Drug: Placebo<br>* Placebo<br>* Other names: saline;|
| Experimental: Placebo, Then Oxytocin<br>Subjects in this arm will receive intramuscular injection of (1 milliliter) saline at the first visit. Then at the next visit, they will receive Intramuscular injection of Oxytocin (Pitocin®), 10 International Units (IU). | Drug: Oxytocin<br>* Oxytocin 10 IU<br>* Other names: Pitocin;Drug: Placebo<br>* Placebo<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluctuation in Pupil Diameter (Hippus) -Pre Drug Administration | Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter in the .1-2 Hz range, termed hippus. Pupil measurements will be made for 20 seconds every 5 minutes for 20 minutes. The Fast Fourier Transform (FFT) essentially takes what looks like a random, noisy signal and distills it into a combination of many sine waves, each with different frequencies and different sizes (think ocean waves, which has the big wave we see and the small up and down wavelets on the top of the water). The primary outcome measure is the size of the largest wave in the frequency range above in this FFT analysis. Its dimensions are milliseconds^2. | From 20 minutes before until study drug injection | 
| Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter in the .1-2 Hz range, termed hippus. Pupil measurements will be made for 20 seconds every 5 minutes until 90 minutes after study drug administration. The Fast Fourier Transform (FFT) essentially takes what looks like a random, noisy signal and distills it into a combination of many sine waves, each with different frequencies and different sizes (think ocean waves, which has the big wave we see and the small up and down wavelets on the top of the water). The primary outcome measure is the size of the largest wave in the frequency range above in this FFT analysis. Its dimensions are milliseconds^2. | For 90 minutes after study drug administration | 
| Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter in the .1-2 Hz range, termed hippus. Pupil measurements will be made for 20 seconds every 5 minutes until 120 minutes after study drug administration. The Fast Fourier Transform (FFT) essentially takes what looks like a random, noisy signal and distills it into a combination of many sine waves, each with different frequencies and different sizes (think ocean waves, which has the big wave we see and the small up and down wavelets on the top of the water). The primary outcome measure is the size of the largest wave in the frequency range above in this FFT analysis. Its dimensions are milliseconds^2. | For 120 minutes after study drug administration | 
| Heart Rate Variability in the High Frequency Range | Magnitude of peak power in the 0.12-0.40 Hz frequency range of the Fast Fourier Transform of heart rate. The Fast Fourier Transform (FFT) essentially takes what looks like a random, noisy signal and distills it into a combination of many sine waves, each with different frequencies and different sizes (think ocean waves, which has the big wave we see and the small up and down wavelets on the top of the water). The primary outcome measure is the size of the largest wave in the frequency range above in this FFT analysis. Its dimensions are milliseconds^2. | From 20 minutes before until study drug injection | 
| Heart Rate Variability in the High Frequency Range | Magnitude of peak power in the 0.12-0.40 Hz frequency range of the Fast Fourier Transform of heart rate. The Fast Fourier Transform (FFT) essentially takes what looks like a random, noisy signal and distills it into a combination of many sine waves, each with different frequencies and different sizes (think ocean waves, which has the big wave we see and the small up and down wavelets on the top of the water). The primary outcome measure is the size of the largest wave in the frequency range above in this FFT analysis. Its dimensions are milliseconds^2. | For 90 minutes after study drug administration | 
| Heart Rate Variability in the High Frequency Range | Magnitude of peak power in the 0.12-0.40 Hz frequency range of the Fast Fourier Transform of heart rate. The Fast Fourier Transform (FFT) essentially takes what looks like a random, noisy signal and distills it into a combination of many sine waves, each with different frequencies and different sizes (think ocean waves, which has the big wave we see and the small up and down wavelets on the top of the water). The primary outcome measure is the size of the largest wave in the frequency range above in this FFT analysis. Its dimensions are milliseconds^2. | For 120 minutes after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteer, Oxytocin, Pupillometry