Chronic Pain Due to Injury
Conditions
Keywords
Healthy Volunteer, Oxytocin, Pupillometry
Brief summary
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
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.
Interventions
DRUGOxytocin
Oxytocin 10 IU
DRUGPlacebo
Placebo
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participant, Investigator, and outcomes assessor will be blinded. The Research Pharmacist will prepare the study medication and hold the randomization.
Intervention model description
Double blinded crossover treatment with oxytocin and placebo (saline)
Eligibility
Sex/Gender
ALL
Age
18 Years to 66 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluctuation in Pupil Diameter (Hippus) -Pre Drug Administration | From 20 minutes before until study drug injection | 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. |
| Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | For 90 minutes after study 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. |
| Heart Rate Variability in the High Frequency Range | From 20 minutes before until study drug injection | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment was performed via advertising in the community and internally within the medical center. Subjects who met inclusion criteria were scheduled for a visit at the Pain Research Clinical Research Unit where the written informed consent was obtained. The enrollment period was 10/24/2019 to 11/01/2021
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin on Study Day 1 and Placebo Study Day 2 Participant received intravenous oxytocin, 10 International Units (IU) on study day 1 and intravenous placebo on study day 2 | 12 |
| Placebo on Study Day 1 and Placebo Participant received intravenous placebo on study day 1 and intravenous oxytocin, 10 International Units (IU) on study day 2 | 10 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Study Day | Altered frequency and times of measurements on both study days | 2 | 0 |
Baseline characteristics
| Characteristic | Oxytocin on Study Day 1 and Placebo Study Day 2 | Total | Placebo on Study Day 1 and Placebo |
|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 12 | 35 years STANDARD_DEVIATION 13 | 35 years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 22 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 21 Participants | 9 Participants |
| Region of Enrollment United States | 12 participants | 22 participants | 10 participants |
| Sex: Female, Male Female | 7 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
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.
Time frame: For 90 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | 1.34 milliseconds^2 | Standard Deviation 0.56 |
| Placebo | Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | 1.52 milliseconds^2 | Standard Deviation 0.68 |
Comparison: Exploratory analysis without power calculationp-value: 0.19t-test, 2 sided
Primary
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.
Time frame: For 120 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | 0.98 milliseconds^2 | Standard Deviation 0.54 |
| Placebo | Fluctuation in Pupil Diameter (Hippus) -Post Drug Administration | 1.49 milliseconds^2 | Standard Deviation 1.39 |
Comparison: Exploratory analysis without power calculationp-value: 0.067t-test, 2 sided
Primary
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.
Time frame: From 20 minutes before until study drug injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Fluctuation in Pupil Diameter (Hippus) -Pre Drug Administration | 1.61 milliseconds^2 | Standard Deviation 1.2 |
| Placebo | Fluctuation in Pupil Diameter (Hippus) -Pre Drug Administration | 1.71 milliseconds^2 | Standard Deviation 1.26 |
Comparison: Exploratory analysis without power calculationp-value: 0.64t-test, 2 sided
Primary
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.
Time frame: From 20 minutes before until study drug injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Heart Rate Variability in the High Frequency Range | 182 milliseconds^2 | Standard Deviation 151 |
| Placebo | Heart Rate Variability in the High Frequency Range | 253 milliseconds^2 | Standard Deviation 296 |
Comparison: Exploratory analysis without power calculationp-value: 0.25t-test, 2 sided
Primary
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.
Time frame: For 90 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Heart Rate Variability in the High Frequency Range | 183 milliseconds^2 | Standard Deviation 158 |
| Placebo | Heart Rate Variability in the High Frequency Range | 300 milliseconds^2 | Standard Deviation 296 |
Comparison: Exploratory analysis without power calculationp-value: 0.058t-test, 2 sided
Primary
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.
Time frame: For 120 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Heart Rate Variability in the High Frequency Range | 247 milliseconds^2 | Standard Deviation 216 |
| Placebo | Heart Rate Variability in the High Frequency Range | 381 milliseconds^2 | Standard Deviation 273 |
Comparison: Exploratory analysis without power calculationp-value: 0.111t-test, 2 sided