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

Effects of Intramuscular Oxytocin on Pupil Diameter and Heart Rate Variability

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain Due to Injury
• Intervention / Treatment: Drug: Placebo; Drug: Oxytocin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 66 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oxytocin First, then Placebo; 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: Placebo; Placebo; Other Names: saline; Drug: Oxytocin; Oxytocin 10 IU; Other Names: Pitocin
EXPERIMENTAL: Placebo, Then Oxytocin; 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: Placebo; Placebo; Other Names: saline; Drug: Oxytocin; Oxytocin 10 IU; Other Names: Pitocin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Norman GJ, Cacioppo JT, Morris JS, Malarkey WB, Berntson GG, Devries AC. Oxytocin increases autonomic cardiac control: moderation by loneliness. Biol Psychol. 2011 Mar;86(3):174-80. doi: 10.1016/j.biopsycho.2010.11.006. Epub 2010 Nov 30.
• Turnbull PR, Irani N, Lim N, Phillips JR. Origins of Pupillary Hippus in the Autonomic Nervous System. Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):197-203. doi: 10.1167/iovs.16-20785.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 24, 2019
• Primary Completion (ACTUAL): November 1, 2021
• Study Completion (ACTUAL): November 1, 2021

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (ACTUAL): September 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Healthy Volunteer; Oxytocin; Pupillometry
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB00060838

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes