Generate a Pharmacodynamic Model of Oxytocin for Peripheral Analgesic Effects

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.

Study Overview

• Status: Terminated
• Conditions: Healthy; Osteoarthritis, Knee
• Intervention / Treatment: Drug: Oxytocin

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

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 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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	Drug: Oxytocin; Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0; Other Names: Pitocin
Other: 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	Drug: Oxytocin; Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0; Other Names: Pitocin
Other: 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	Drug: Oxytocin; Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0; Other Names: Pitocin
Other: 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	Drug: Oxytocin; Oxytocin, 8.2 IU, administered by 30minute IV infusion starting at time 0; Other Names: Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2-10 minutes after starting oxytocin infusion, depending on Arm
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.	17-25 minutes after starting oxytocin infusion, depending on Arm
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.	32-40 minutes after starting oxytocin infusion, depending on Arm
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.	47-55 minutes after starting oxytocin infusion, depending on Arm
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.	62-70 minutes after starting oxytocin infusion, depending on Arm

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: James C Eisenach, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): November 25, 2020
• Study Completion (Actual): November 25, 2020

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pituitary Hormones, Posterior; Pituitary Hormones; Oxytocin
• Other Study ID Numbers: IRB00066136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be provided upon request.
• IPD Sharing Time Frame: Data will be available upon posting results to a preprint server, anticipated to occur by the end of the first quarter of 2026
• IPD Sharing Access Criteria: For the purpose of pharmacokinetic / pharmacodynamic modeling or meta-analyses / review publications.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

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