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Generate and Test the Reliability of a PD Model of OXT on Pupillary Hippus as a Measure of CNS Activity

Phase 2
Recruiting
Conditions
Chronic Pain
Osteoarthritis, Knee
Interventions
Drug: Placebo
Registration Number
NCT04427709
Lead Sponsor
Wake Forest University Health Sciences
Brief Summary

The purpose of this research is to evaluate the effects of oxytocin (naturally occurring hormone) given by an intramuscular (IM; into the muscle) injection, has on your parasympathetic nervous system. The parasympathetic nervous system is the part of the involuntary nervous system that is sometimes called the "rest and digest" system; the parasympathetic system conserves energy as it slightly slows the heart rate, increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.

Detailed Description

This is a single site study at Wake Forest School of Medicine. Healthy volunteers and patients with advanced knee arthritis being seen in the Orthopedic Clinic in consultation for potential total knee arthroplasty will be recruited after their doctor visit if the decision is made not to perform surgery at this time.

Study participants will come to the Pain Clinical Research Unit on 2 occasions. On these visits, they will receive an intramuscular (i.m.) injection of placebo or oxytocin, 25 micrograms (μg) (Pitocin®), obtained from the research pharmacy. The order in this cross-over study will be randomized and double blind, and the studies separated by at least 48 hours. Every 2.5 minutes beginning 20 minutes before injection and until 180 minutes after injection oscillation in pupil diameter at low frequency (hippus) will be obtained using an infrared pupilometer, in which they focus on a central point of gaze for 20 seconds. Hippus, a measure of parasympathetic output to the pupil and affected by central actions of oxytocin as described in preliminary data, will be calculated as the magnitude of power in the 0-0.25 Hertz (Hz) bin of the spectral analysis of pupil diameter, after removing blink and saccade artifacts. After 180 minutes the study participant will be discharged from the Pain Clinical Research Unit.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
38
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 eye pathology, eye surgery, or taking topical eye medications, or any disease process that would cause motor tremors or excessive eye movements.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Oxytocin First, then PlaceboPlaceboSubjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®) first then placebo injection.
Placebo, Then OxytocinPlaceboSubjects in this arm will receive Intramuscular placebo injection first then oxytocin injection
Oxytocin First, then PlaceboOxytocinSubjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®) first then placebo injection.
Placebo, Then OxytocinOxytocinSubjects in this arm will receive Intramuscular placebo injection first then oxytocin injection
Primary Outcome Measures
NameTimeMethod
Fluctuation in Pupil Diameter (Hippus) -Pre drug administrationBaseline before study drug administration

Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter.

One measure of coefficient of variation at each time period. It is calculated by the amount of variability in a window of time.

Every 2.5 minutes beginning 20 minutes before the intramuscular injection of placebo or oxytocin, 25 micrograms.

Fluctuation in Pupil Diameter (Hippus) -Post drug administrationup to 180 minutes after study drug administration

Magnitude of power at the dominant frequency in the Fourier transform of pupil diameter.

One measure of coefficient of variation at each time period. It is calculated by the amount of variability in a window of time.

Every 2.5 minutes for 180 after intramuscular injection of placebo or oxytocin, 25 micrograms.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Wake Forest Baptist Health

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Winston-Salem, North Carolina, United States

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