Apply the PD Model of Peripheral Oxytocin Action to a Multimodal Stimulus

Apply the Pharmacodynamic Model of Peripheral Oxytocin Action to a Multimodal Stimulus That Increases (Heat) or Decreases (Vibration) Pain Perception

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 are recruited. Each study participant will have an IV catheter placed. After placement of the IV catheter oxytocin will be given by IV infusion of oxytocin or placebo (inactive solution). The investigators will perform some tests to evaluate how oxytocin changes perceptions on the skin. The investigators will study a painful perception by placing a probe on the skin and heating it to 116.6 degrees Fahrenheit for 30 seconds and a vibratory stimulus will be applied to the forearm with vibration begun at a 1 kHz frequency and decreased at a rate of 25 Hz/sec until the subject first perceives the vibration. Each study participant will score any pain that is experienced on a 0 to 10 scale and will report when the vibration is detected. Each participant will receive oxytocin and placebo in a random order and will be blinded to group they are receiving.

Study Overview

• Status: Withdrawn
• Conditions: Pain, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Oxytocin

Detailed Description

The investigators aim to create pharmacokinetic/pharmacodynamic (PK/PD) models for oxytocin action at peripheral sites and at central sites as they relate to sensory transmission and pain. This is the last of 4 studies to accomplish generation, validation, and application of a PK/PD model for oxytocin in the periphery. Its goal is to apply the PK/PD model generated in previous protocols and Validate a pharmacodynamic model of oxytocin for peripheral analgesic effects to a more complex sensory stimulus that stimulates nerve fibers which result in pain from a heat stimulus and those which reduce pain from vibration, similar to brushing or rubbing an area of pain. The investigators do this because oxytocin in animals affects these nerve fibers in the periphery in different ways - it increases the activity of the vibration/rubbing sensitive fibers and decreases the activity of the pain fibers. As such, The investigators expect that the effect of oxytocin on pain from this mixed stimulus of heat and vibration will be much more pronounced than that seen with the purely painful stimulus used in previous studies in this series.

This is a double-blind, crossover study in which oxytocin or placebo is infused. In this study healthy people are recruited for a 2 day double-blind, crossover study. They will come to the Clinical Research Unit and one intravenous catheter (IV) inserted in the forearm for oxytocin or placebo infusion. Participants will be given a steady rate intravenous infusion of oxytocin at a targeted dose or placebo for 30 minutes. At 5, 15, and 30 minutes after starting the infusion, pain report to the 47°Celsius, 30-second stimulus alone or with ½ VT vibration (randomized order) will be obtained. Participants will return at least 24 hours later and receive the opposite infusion and testing.

• Study Type: Interventional
• 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 or 2.
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.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Oxytocin First, then Placebo; Oxytocin administered intravenously for the first half of the study and then will receive intravenous placebo for the second half.	Drug: Placebo; Placebo administered intravenously; Drug: Oxytocin; Oxytocin administered intravenously; Other Names: Pitocin
Other: Placebo, Then Oxytocin; Placebo administered intravenously for the first half of the study and then will receive intravenous oxytocin for the second half.	Drug: Placebo; Placebo administered intravenously; Drug: Oxytocin; Oxytocin administered intravenously; Other Names: Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heat pain with vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	Baseline before infusion
Heat pain with vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	5 minutes post infusion initiation
Heat pain with vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	15 minutes post infusion initiation
Heat pain with vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C with simultaneous vibration will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	30 minutes post infusion initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heat pain without vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	Baseline
Heat pain without vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	5 minutes post infusion initiation
Heat pain without vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	15 minutes post infusion initiation
Heat pain without vibration	Pain at the end of 30 sec of heating the skin to 47 degrees C will be determined. Pain will be measured using a verbal Pain Scale 0-10. 0 is equivalent to NO PAIN and 10 is equivalent to WORST PAIN IMAGINABLE.	30 minutes post infusion initiation

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 (Estimated): January 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB00066443

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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