Generate a Pharmacodynamic Model of Oxytocin for Peripheral Analgesic Effects

Osteoarthritis, Knee Clinical Trial

Official title:

Generate a Pharmacodynamic Model of Oxytocin for Peripheral Analgesic Effects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04431206
• Other study ID #: IRB00066136
• Status: Recruiting
• Phase: Phase 2
• Start date: November 4, 2020
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Wake Forest University Health Sciences
• Contact: Regina Curry, RN
• Phone: 336-716-4294
• Email: RECURRY[@]WAKEHEALTH.EDU
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: March 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis, Knee

Intervention

Drug:
• Oxytocin
Oxytocin administered by IV infusion

Locations

Country	Name	City	State
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamics of heat pain after oxytocin	3 Minutes prior to the 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 will be determined according to pain rating during screening visit.	3 minutes prior to Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	12 Minutes after the Oxytocin infusion is initiated 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 will be determined according to pain rating during screening visit.	12 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	27 Minutes after the Oxytocin infusion is initiated 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 will be determined according to pain rating during screening visit.	27 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	42 Minutes after the Oxytocin infusion is initiated 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 will be determined according to pain rating during screening visit.	42 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	57 Minutes after the Oxytocin infusion is initiated 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 will be determined according to pain rating during screening visit.	57 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	Simultaneously with the beginning of the 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 will be determined according to pain rating during screening visit.	Beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	15 minutes after the initiation of the 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 will be determined according to pain rating during screening visit.	15 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	30 minutes after the initiation of the 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 will be determined according to pain rating during screening visit.	30 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	45 minutes after the initiation of the 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 will be determined according to pain rating during screening visit.	45 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	60 minutes after the initiation of the 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 will be determined according to pain rating during screening visit.	60 minutes after the start of Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	2 minutes after initiation of Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. 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 will be determined according to pain rating during screening visit.	2 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	17 minutes after initiation of Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	17 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	32 minutes after initiation of Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	32 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	47 minutes after initiation of Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	47 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	62 minutes after initiation of Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	62 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	5 minutes after the beginning of the Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	5 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	20 minutes after the beginning of the Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	20 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	35 minutes after the beginning of the Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	35 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	50 minutes after the beginning of the Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	50 minutes after the beginning of the Oxytocin infusion
Primary	Pharmacodynamics of heat pain after oxytocin	65 minutes after the beginning of the Oxytocin infusion; Pain at the end of 5 minutes of heating the skin to 45 - 47 degrees C will be determined before, during and after infusions in order to create a PD model and validate the PK/PD model. Pain at the end of 5 minutes of heating the skin to 45 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 will be determined according to pain rating during screening visit.	65 minutes after the beginning of the Oxytocin infusion