Healthy, Osteoarthritis, Knee
Conditions
Brief summary
This is a study of participants that will receive an intravenous (IV) infusion of oxytocin (naturally occurring hormone that is made in the brain). In this study healthy volunteers and people with knee arthritis so severe that they may need joint replacement are recruited for a one day study. Each study participant will have an IV catheter placed. After placement of the IV catheter oxytocin will be given by IV infusion. Investigators will perform some tests to evaluate how oxytocin changes perceptions on the skin. Investigators will study a painful perception by placing a probe on the skin and heating it to 113 -117 degrees Fahrenheit (F) for 5 minutes. Each study participant will score any pain that is experienced on a 0 to 10 scale, and most people find that pain rises during the 5 minutes, but remains mild, usually around only 1 or 2 on the 0 to 10 scale. The 5 minute heating temperature will be determined according to the subjects pain rating during the screening visit. The main goal of the study is to determine the effect of oxytocin during and after a fixed rate intravenous infusion on reduction in pain to a sustained heat stimulus in order to generate a model for peripheral analgesia.
Detailed description
In this study healthy people or those with knee arthritis so severe that they may need joint replacement are recruited for a one day study. Study participants will come to the Clinical Research Unit (CRU) and one intravenous (IV) catheter will be inserted in the forearm for oxytocin infusion. Participants in this study will receive oxytocin at a steady rate for 30 minutes. This information will be analyzed by another group at Stanford University in the Pharmacokinetic/Pharmacodynamic (PK/PD) Core part of this application. Mathematics will be utilized to calculate how quickly oxytocin moves from the blood to where it reduces pain. Investigators will also do a pain test to determine how much oxytocin reduces pain. For this Investigators will place a probe on the skin and heat it to 113 - 117 degrees for 5 minutes. Study participants will score any pain they feel on a 0 to 10 scale, and most people find that pain rises during the 5 minutes, but remains mild, usually around only 1 or 2 on the 0 to 10 scale.
Interventions
DRUGOxytocin
Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
All arms receive the same IV oxytocin 30-minute infusion. Participants are randomly assigned for heat pain testing every 15 min for 60 min beginning at either 2, 5, 7, or 10 minutes from the beginning of the IV oxytocin 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 °C to the lower calf.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First Verbal Pain Score After Beginning IV Oxytocin Infusion | 2-10 minutes after starting oxytocin infusion, depending on Arm | Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit. |
| Second Verbal Pain Score After Beginning IV Oxytocin Infusion | 17-25 minutes after starting oxytocin infusion, depending on Arm | Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit. |
| Third Verbal Pain Score After Beginning IV Oxytocin Infusion | 32-40 minutes after starting oxytocin infusion, depending on Arm | Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit. |
| Fourth Verbal Pain Score After Beginning IV Oxytocin Infusion | 47-55 minutes after starting oxytocin infusion, depending on Arm | Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit. |
| Fifth Verbal Pain Score After Beginning IV Oxytocin Infusion | 62-70 minutes after starting oxytocin infusion, depending on Arm | Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit. |
Countries
United States
Participant flow
Recruitment details
Healthy participants were recruited from the community from October 15, 2020 through November 15, 2020 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 2 Minutes Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 2 minutes after starting the intervention, then every 15 minutes for 60 minutes
Oxytocin: Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0 | 2 |
| Verbal Pain Score at 5 Minutes Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 5 minutes after starting the intervention, then every 15 minutes for 60 minutes
Oxytocin: Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0 | 1 |
| Verbal Pain Score at 7 Minutes Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 7 minutes after starting the intervention, then every 15 minutes for 60 minutes
Oxytocin: Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0 | 2 |
| Verbal Pain Score at 10 Minutes Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 10 minutes after starting the intervention, then every 15 minutes for 60 minutes
Oxytocin: Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0 | 2 |
| Total | 7 |
Baseline characteristics
| Characteristic | Verbal Pain Score at 2 Minutes | Total | Verbal Pain Score at 10 Minutes | Verbal Pain Score at 7 Minutes | Verbal Pain Score at 5 Minutes |
|---|---|---|---|---|---|
| Age, Continuous | 36 years | 26 years | 25 years | 22.5 years | 34 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 2 participants | 7 participants | 2 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Verbal pain score at the end of 5 minute skin heating | 3.0 units on a scale | 3.1 units on a scale | 2.0 units on a scale | 3.5 units on a scale | 5.0 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Fifth Verbal Pain Score After Beginning IV Oxytocin Infusion
Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit.
Time frame: 62-70 minutes after starting oxytocin infusion, depending on Arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verbal Pain Score at 2 Minutes | Fifth Verbal Pain Score After Beginning IV Oxytocin Infusion | 3.0 units on a scale |
| Verbal Pain Score at 5 Minutes | Fifth Verbal Pain Score After Beginning IV Oxytocin Infusion | 2.0 units on a scale |
| Verbal Pain Score at 7 Minutes | Fifth Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.5 units on a scale |
| Verbal Pain Score at 10 Minutes | Fifth Verbal Pain Score After Beginning IV Oxytocin Infusion | 0.5 units on a scale |
Primary
First Verbal Pain Score After Beginning IV Oxytocin Infusion
Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit.
Time frame: 2-10 minutes after starting oxytocin infusion, depending on Arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verbal Pain Score at 2 Minutes | First Verbal Pain Score After Beginning IV Oxytocin Infusion | 3.5 units on a scale |
| Verbal Pain Score at 5 Minutes | First Verbal Pain Score After Beginning IV Oxytocin Infusion | 4.0 units on a scale |
| Verbal Pain Score at 7 Minutes | First Verbal Pain Score After Beginning IV Oxytocin Infusion | 3.5 units on a scale |
| Verbal Pain Score at 10 Minutes | First Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.5 units on a scale |
Primary
Fourth Verbal Pain Score After Beginning IV Oxytocin Infusion
Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit.
Time frame: 47-55 minutes after starting oxytocin infusion, depending on Arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verbal Pain Score at 2 Minutes | Fourth Verbal Pain Score After Beginning IV Oxytocin Infusion | 2.0 units on a scale |
| Verbal Pain Score at 5 Minutes | Fourth Verbal Pain Score After Beginning IV Oxytocin Infusion | 3.0 units on a scale |
| Verbal Pain Score at 7 Minutes | Fourth Verbal Pain Score After Beginning IV Oxytocin Infusion | 2.0 units on a scale |
| Verbal Pain Score at 10 Minutes | Fourth Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.0 units on a scale |
Primary
Second Verbal Pain Score After Beginning IV Oxytocin Infusion
Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit.
Time frame: 17-25 minutes after starting oxytocin infusion, depending on Arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verbal Pain Score at 2 Minutes | Second Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.5 units on a scale |
| Verbal Pain Score at 5 Minutes | Second Verbal Pain Score After Beginning IV Oxytocin Infusion | 3.0 units on a scale |
| Verbal Pain Score at 7 Minutes | Second Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.5 units on a scale |
| Verbal Pain Score at 10 Minutes | Second Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.0 units on a scale |
Primary
Third Verbal Pain Score After Beginning IV Oxytocin Infusion
Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C 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 is determined by pain rating during screening visit.
Time frame: 32-40 minutes after starting oxytocin infusion, depending on Arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verbal Pain Score at 2 Minutes | Third Verbal Pain Score After Beginning IV Oxytocin Infusion | 3.0 units on a scale |
| Verbal Pain Score at 5 Minutes | Third Verbal Pain Score After Beginning IV Oxytocin Infusion | 4.0 units on a scale |
| Verbal Pain Score at 7 Minutes | Third Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.0 units on a scale |
| Verbal Pain Score at 10 Minutes | Third Verbal Pain Score After Beginning IV Oxytocin Infusion | 1.0 units on a scale |