Acute Pain, Chronic Pain, Healthy Volunteer
Conditions
Keywords
Acute pain, Chronic Pain, Oxytocin
Brief summary
The goal of this clinical trial is to learn about oxytocin ( a naturally occurring hormone made in the brain that transmits messages) and the effects it may have on thermal heat pain after intravenous administration. The main question it aims to define is the time course of change in pain score after a 5 minute heating of the skin administered at intervals during and following infusion of intravenous oxytocin in order to create a Pharmacokinetic and a Pharmacodynamic model for oxytocin-induced analgesia. Participants will be asked to rate thermal heat temperatures before, during and after the intravenous infusion of oxytocin.
Detailed description
The primary objective is to define the time course of change in pain score after a 5 minute heating of the skin applied at intervals during and following infusion of intravenous oxytocin in order to create a Pharmacokinetic and Pharmacodynamic model for oxytocin-induced analgesia.
Interventions
DRUGOxytocin
Intravenous oxytocin
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
All subjects will receive two 30-minute infusions of oxytocin, 10 IU. The second infusion will be given 30 minutes after the completion of the first infusion. The first 8 subjects report pain at the end of 5 minutes of skin heating at intervals beginning 15 minutes after starting the first infusion. The remaining subjects will be randomized to report pain at the end of 5 minutes of skin heating at intervals beginning at either 10 or 20 minutes after starting the first infusion.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female \> 18 and \< 75 years of age, Body Mass Index (BMI) \<40. 2. Generally in good health as determined by the Principal Investigator based on prior medical history, American Society of Anesthesiologists physical status 1, 2, or 3. 3. For healthy volunteers, normal blood pressure (systolic 90-140 mmHg; diastolic 50-90 mmHg) resting heart rate 45-100 beats per minute) without medication. For knee arthritis subjects, normal blood pressure or, for those with hypertension, pressure controlled with anti-hypertensives and with a resting heart rate 45-100 beats per minute. 4. Female subjects of child-bearing potential and those \< 1 year post-menopausal, must be practicing highly effective methods of birth control such as hormonal methods (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal jellies or cream), or total abstinence from heterosexual intercourse for a minimum of 1 full cycle before study drug administration.
Exclusion criteria
1. Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin® 2. Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk (active gynecologic disease in which increased tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the subject's compliance with study procedures, or compromise the quality of the data 3. 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 4. Subjects with neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis. 5. Subjects with current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval. 6. Subjects with past or current history of hyponatremia or at risk for hyponatremia; anyone taking thiazide diuretics, loop diuretics, combination diuretics, lithium, carbamazepine, enalapril, Ramipril, celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, glipizide, omeprazole, pantoprazole, desmopressin, SSRI's, MAOI, or the recreational drug ecstasy. 7. Subjects with a known latex allergy. 8. Subjects with a pain score rating of 1 or less during the initial training session to a 5 minute heating of 45°C- 47 °Celsius to the lower calf.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Pain Score at the End of 5 Minutes of Skin Heating | 5-7 days | Verbal pain score measured at one minute intervals during the 5 minute heating of the skin at intervals up to180 minutes after the initiation of the oxytocin infusions, then at 24 hours and 5-7 days after oxytocin infusions. The verbal pain score at the 5 minute measurement is the primary pharmacodynamic outcome for the purpose of modeling the pharmacokinetic-pharmacodynamic relationship. Note that the timing of the primary outcome differs among arms. Pain intensity report will be recorded each minute during the heating of the skin to 45 - 47 degrees Celsius . Pain will be determined using a Verbal Pain scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to THE WORST PAIN IMAGINABLE. Heating temperature will be determined according to pain rating during screening visit. |
Countries
United States
Participant flow
Recruitment details
Healthy participants were recruited from the community from Aug 17, 2023 through October 2, 2024 via IRB-approved advertisements and IRB-approved lists of previous participants who agreed to be contacted for future studies. They were recruited by phone and provided written informed consent at the day of the training visit.
Participants by arm
| Arm | Count |
|---|---|
| Verbal Pain Score at 10 Minutes In this arm the first primary outcome measure (verbal pain report at the end of 5 minutes of skin heating) is obtained at 10 minutes after starting the intervention, then every 15 minutes until 115 minutes and at 180 minutes after starting the intervention. The primary outcome is also measured on separate study visits 24 hours and between 5-7 days after starting the intervention. | 8 |
| Verbal Pain Score at 15 Minutes In this arm the first primary outcome measure (verbal pain report at the end of 5 minutes of skin heating) is obtained at 15 minutes after starting the intervention, then every 15 minutes until 120 minutes and at 180 minutes after starting the intervention. The primary outcome is also measured on separate study visits 24 hours and between 5-7 days after starting the intervention. | 8 |
| Verbal Pain Score at 20 Minutes In this arm the first primary outcome measure (verbal pain report at the end of 5 minutes of skin heating) is obtained at 20 minutes after starting the intervention, then every 15 minutes until 125 minutes and at 180 minutes after starting the intervention. The primary outcome is also measured on separate study visits 24 hours and between 5-7 days after starting the intervention. | 9 |
| Total | 25 |
Baseline characteristics
| Characteristic | Verbal Pain Score at 10 Minutes | Total | Verbal Pain Score at 20 Minutes | Verbal Pain Score at 15 Minutes |
|---|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 19 | 38 years STANDARD_DEVIATION 19 | 42 years STANDARD_DEVIATION 21 | 24 years STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 25 Participants | 9 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 22 Participants | 8 Participants | 6 Participants |
| Region of Enrollment United States | 8 participants | 25 participants | 9 participants | 8 participants |
| Sex: Female, Male Female | 4 Participants | 13 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 12 Participants | 4 Participants | 4 Participants |
| Verbal pain score at the end of 5 minute skin heating | 3.9 units on a scale STANDARD_DEVIATION 0.8 | 4.0 units on a scale STANDARD_DEVIATION 1.2 | 4.1 units on a scale STANDARD_DEVIATION 1.8 | 3.9 units on a scale STANDARD_DEVIATION 0.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 2 / 8 | 4 / 8 | 5 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 9 |
Outcome results
Primary
Verbal Pain Score at the End of 5 Minutes of Skin Heating
Verbal pain score measured at one minute intervals during the 5 minute heating of the skin at intervals up to180 minutes after the initiation of the oxytocin infusions, then at 24 hours and 5-7 days after oxytocin infusions. The verbal pain score at the 5 minute measurement is the primary pharmacodynamic outcome for the purpose of modeling the pharmacokinetic-pharmacodynamic relationship. Note that the timing of the primary outcome differs among arms. Pain intensity report will be recorded each minute during the heating of the skin to 45 - 47 degrees Celsius . Pain will be determined using a Verbal Pain scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to THE WORST PAIN IMAGINABLE. Heating temperature will be determined according to pain rating during screening visit.
Time frame: 5-7 days
Population: There was one outlier in the Verbal Pain Score at 20 Minutes group, whose data was not included in the primary analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 115 minutes after starting oxytocin infusion (first arm only) | 2.6 score on a scale | Standard Deviation 0.5 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 70 minutes after starting oxytocin infusion (first arm only) | 2.3 score on a scale | Standard Deviation 1.3 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 24 hours after starting oxytocin infusion (all arms) | 3.0 score on a scale | Standard Deviation 1.1 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 100 minutes after starting oxytocin infusion (first arm only) | 2.5 score on a scale | Standard Deviation 1.2 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 85 minutes after starting oxytocin infusion (first arm only) | 2.3 score on a scale | Standard Deviation 0.9 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 10 minutes after starting oxytocin infusion (first arm only) | 3.3 score on a scale | Standard Deviation 0.9 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 40 minutes after starting oxytocin infusion (first arm only) | 2.8 score on a scale | Standard Deviation 1 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 25 minutes after starting oxytocin infusion (first arm only) | 3.1 score on a scale | Standard Deviation 1.3 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 180 minutes after starting oxytocin infusion (all arms) | 2.8 score on a scale | Standard Deviation 1.3 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 55 minutes after starting oxytocin infusion (first arm only) | 3.0 score on a scale | Standard Deviation 0.9 |
| Verbal Pain Score at 10 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 5-7 days after starting oxytocin infusion (all arms) | 3.5 score on a scale | Standard Deviation 1.4 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 90 minutes after starting oxytocin infusion (second arm only) | 2.1 score on a scale | Standard Deviation 0.9 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 15 minutes after starting oxytocin infusion (second arm only) | 3.1 score on a scale | Standard Deviation 0.9 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 30 minutes after starting oxytocin infusion (second arm only) | 3.6 score on a scale | Standard Deviation 1.3 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 45 minutes after starting oxytocin infusion (second arm only) | 2.4 score on a scale | Standard Deviation 1.3 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 60 minutes after starting oxytocin infusion (second arm only) | 2.6 score on a scale | Standard Deviation 1 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 75 minutes after starting oxytocin infusion (second arm only) | 2.6 score on a scale | Standard Deviation 1.1 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 105 minutes after starting oxytocin infusion (second arm only) | 2.0 score on a scale | Standard Deviation 0.8 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 120 minutes after starting oxytocin infusion (second arm only) | 2.1 score on a scale | Standard Deviation 1.1 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 180 minutes after starting oxytocin infusion (all arms) | 1.7 score on a scale | Standard Deviation 1.7 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 24 hours after starting oxytocin infusion (all arms) | 2.6 score on a scale | Standard Deviation 1.4 |
| Verbal Pain Score at 15 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 5-7 days after starting oxytocin infusion (all arms) | 2.9 score on a scale | Standard Deviation 1.1 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 24 hours after starting oxytocin infusion (all arms) | 3.7 score on a scale | Standard Deviation 2 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 125 minutes after starting oxytocin infusion (third arm only) | 3.3 score on a scale | Standard Deviation 2.5 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 50 minutes after starting oxytocin infusion (third arm only) | 3.1 score on a scale | Standard Deviation 2.2 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 20 minutes after starting oxytocin infusion (third arm only) | 3.4 score on a scale | Standard Deviation 1.9 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 180 minutes after starting oxytocin infusion (all arms) | 3.5 score on a scale | Standard Deviation 2.2 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 35 minutes after starting oxytocin infusion (third arm only) | 3.4 score on a scale | Standard Deviation 2.2 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 95 minutes after starting oxytocin infusion (third arm only) | 3.2 score on a scale | Standard Deviation 2.1 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 80 minutes after starting oxytocin infusion (third arm only) | 3.1 score on a scale | Standard Deviation 2.2 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 5-7 days after starting oxytocin infusion (all arms) | 3.7 score on a scale | Standard Deviation 1.9 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 110 minutes after starting oxytocin infusion (third arm only) | 2.9 score on a scale | Standard Deviation 2.3 |
| Verbal Pain Score at 20 Minutes | Verbal Pain Score at the End of 5 Minutes of Skin Heating | 65 minutes after starting oxytocin infusion (third arm only) | 3.2 score on a scale | Standard Deviation 2.1 |