Inflammatory Responses to Acute and Chronic Opioid Exposure in Humans

We aim to examine the extent to which inflammation is affected by acute and chronic opioid exposure.

Study Overview

• Status: Terminated
• Conditions: Inflammation
• Intervention / Treatment: Drug: Morphine Sulfate

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronic Opioid Exposure; 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; 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.; Other Names: Kadian; MS Contin; Morphine Sulfate ER; Roxanol
Experimental: Acute Opioid Exposure; 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; 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.; Other Names: Kadian; MS Contin; Morphine Sulfate ER; Roxanol

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

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: November 9, 2009
• First Submitted That Met QC Criteria: December 12, 2012
• First Posted (Estimate): December 17, 2012

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 6, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation, opioids, immune system
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: SU-10212009-4201

Plan for Individual participant data (IPD)

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