Inflammatory Responses to Acute and Chronic Opioid Exposure in Humans

Study Overview
=================
Brief Summary
-----------------
We aim to examine the extent to which inflammation is affected by acute and chronic opioid exposure.

Detailed Description
-----------------
We are interested in learning how the immune system and the inflammation process is effected by acute and chronic opioid exposure. Preliminary evidence in animal models show that acute opioid exposure leads to decreased inflammatory responses, while chronic opioid exposure causes increased inflammatory responses, as measured by local cytokine release at the site of injury. Translating these findings to humans will lead to important new mechanistic knowledge that may ultimately improve our ability to treat pain.

Official Title
-----------------
Inflammatory Responses to Acute and Chronic Opioid Exposure in Humans

Conditions
-----------------
Inflammation

Intervention / Treatment
-----------------
* Drug: Morphine Sulfate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-60 years old Healthy volunteer Not allergic to remifentanil Exclusion Criteria: Patients younger than 18 or older than 70 Patients unwilling or unable to follow study instructions Patients who don't speak English Patients who are taking prescription opioid medications (e.g. vicodin, percocet) or are unwilling to refrain from taking anti-inflammatory medications such as Advil or Naproxen during 2 weeks prior to and during the 1 month study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic Opioid Exposure<br>15mg sustained release morphine sulfate, with a maximum dose of 120mg. Patients will be titrated up to a maximum dose of 8 pills a day for one month. | Drug: Morphine Sulfate<br>* 15mg sustained release morphine sulfate, with a maximum dose of 120mg. Patients will be titrated up to a maximum dose of 8 pills a day for one month.<br>* Other names: Kadian;|
| Experimental: Acute Opioid Exposure<br>15mg sustained release morphine sulfate, with a maximum dose of 120mg. Patients will be titrated up to a maximum dose of 8 pills a day for one month. | Drug: Morphine Sulfate<br>* 15mg sustained release morphine sulfate, with a maximum dose of 120mg. Patients will be titrated up to a maximum dose of 8 pills a day for one month.<br>* Other names: Kadian;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Cytokine Release | 5 CCs of blood are drawn on day 1 and day 30. | Changes in cytokine release are compared between blood samples drawn on Day 1 and Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laser Doppler Images | The laser doppler is a noninvasive, painless measurement of superficial perfusion that reflects inflammation. Laser doppler images will be taken once per study visit. | Changes in laser doppler images are measured between images taken on Day 1 and Day 30 | 
| Peltier Device-Heat Pain | A hand-held 0.6x0.6 inch metal probe will be brought into contact with the patient's skin. Starting at 95 F, the probe temperature will increase at a rate of 1.8 F per second. The patient will be asked to push a button of a hand-held device as soon as the patient feels pain. | Differences in heat pain are assessed between measurements taken on Day 1 and Day 30 | 
| Mechanical Pain Stimuli | Pain sensitivity will be tested with three different mechanical stimuli that can elicit mild pain: Stroking stimulus: skin will be tested with a brush that is moved three times across the lesion Punctuated stimulus: a metal rod (1/100 of an inch in diameter) mounted onto 10 different weights (0.03-2.9 ounces) will repetitively be placed onto the skin Blunt stimulus: a flat probe (0.4 inch in diameter) will be placed five times onto the patient's skin | Changes in mechanical pain stimuli will be assessed between measurements taken on Day 1 and Day 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inflammation, opioids, immune system