Clinical trial NCT04433741: Apply the PD Model of Peripheral Oxytocin Action to a Multimodal Stimulus
Official title: Apply the Pharmacodynamic Model of Peripheral Oxytocin Action to a Multimodal Stimulus That Increases (Heat) or Decreases (Vibration) Pain Perception
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Pain, Chronic
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Cross over model: each participant will be randomized to receive oxytocin and placebo in a random order
Primary purpose: BASIC_SCIENCE

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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Heat pain with vibration
timeFrame: Baseline before infusion
measure: Heat pain with vibration
timeFrame: 5 minutes post infusion initiation
measure: Heat pain with vibration
timeFrame: 15 minutes post infusion initiation
measure: Heat pain with vibration
timeFrame: 30 minutes post infusion initiation
Secondary outcomes:
measure: Heat pain without vibration
timeFrame: Baseline
measure: Heat pain without vibration
timeFrame: 5 minutes post infusion initiation
measure: Heat pain without vibration
timeFrame: 15 minutes post infusion initiation
measure: Heat pain without vibration
timeFrame: 30 minutes post infusion initiation
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: James C Eisenach, MD
role: PRINCIPAL_INVESTIGATOR
References: