Defining a PK and PD Model for Peripheral Analgesia After IV Oxytocin

Defining a Pharmacokinetic and Pharmacodynamic Model for Peripheral Analgesia After Intravenous Oxytocin

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Acute Pain; Healthy Volunteer
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 25
• 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: 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 °Celsius 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Verbal Pain Score at 10 Minutes; Two 30 minute infusions of oxytocin, 10 IU, will be administered. The second infusion will be given 30 minutes after the completion of the first infusion. 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 first oxytocin infusion.	Drug: Oxytocin; Intravenous oxytocin; Other Names: Pitocin
Other: Verbal Pain Score at 15 Minutes; Two 30 minute infusions of oxytocin, 10 IU, will be administered. The second infusion will be given 30 minutes after the completion of the first infusion. 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 first oxytocin infusion.	Drug: Oxytocin; Intravenous oxytocin; Other Names: Pitocin
Other: Verbal Pain Score at 20 Minutes; Two 30 minute infusions of oxytocin, 10 IU, will be administered. The second infusion will be given 30 minutes after the completion of the first infusion. 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 first oxytocin infusion.	Drug: Oxytocin; Intravenous oxytocin; Other Names: Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5-7 days

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: James C Eisenach, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Actual): October 2, 2024
• Study Completion (Actual): October 2, 2024

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: June 23, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Pain; Oxytocin; Acute pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Acute Pain; 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: IRB00097699; 1P01NS119159-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Statistical programs in the data analysis will be written in R. The software and anonymized data will be included both as digital supplements in the published papers and will be posted on GitHub under github.com/StevenLShafer. Interested investigators will be able to reproduce the published analyses from these files. Consistent with the posting of software and data to the OpenTCI initiative, the software and de-identified data will be made available with "no strings attached," enabling investigators to freely use the data to inform or supplement additional research without restriction. Data to be made available are oxytocin dose, times of pharmacodynamic measures (relative to the start of dosing), simulated plasma oxytocin concentrations at those times for each subject, and age, weight, and sex for each subject.
• IPD Sharing Time Frame: Data will become available upon publication or upon posting results in ClinicalTrials.gov, whichever comes first, with no expiration.
• IPD Sharing Access Criteria: These data are freely shared to all and will be posted at the URL below
• 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