Inflammatory Responses to Acute and Chronic Opioid Exposure in Humans

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01749826
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 42
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Inflammation	Drug: Morphine Sulfate	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Inflammatory Responses to Acute and Chronic Opioid Exposure in Humans
• Actual Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

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: MS Contin Morphine Sulfate ER Roxanol Kadian
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: MS Contin Morphine Sulfate ER Roxanol Kadian

Outcome Measures

Primary Outcome Measures

1. Changes in Cytokine Release [Changes in cytokine release are compared between blood samples drawn on Day 1 and Day 30]

   5 CCs of blood are drawn on day 1 and day 30.

Secondary Outcome Measures

1. Laser Doppler Images [Changes in laser doppler images are measured between images taken on Day 1 and Day 30]

   The laser doppler is a noninvasive, painless measurement of superficial perfusion that reflects inflammation. Laser doppler images will be taken once per study visit.

2. Peltier Device-Heat Pain [Differences in heat pain are assessed between measurements taken on Day 1 and Day 30]

   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.

3. Mechanical Pain Stimuli [Changes in mechanical pain stimuli will be assessed between measurements taken on Day 1 and Day 30]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Dr Larry Fu-nien Chu, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Larry Fu-nien Chu, Associate Professor of Anesthesia, Stanford University
• ClinicalTrials.gov Identifier: NCT01749826
• Other Study ID Numbers: SU-10212009-4201
• First Posted: Dec 17, 2012
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Larry Fu-nien Chu, Associate Professor of Anesthesia, Stanford University: Inflammation, opioids, immune system
• Additional relevant MeSH terms: Inflammation; Morphine

Study Results

Participant Flow

Arm/Group Title	Chronic Opioid Exposure	Acute Opioid Exposure
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	20	0
COMPLETED	0	0
NOT COMPLETED	20	0

Baseline Characteristics

Arm/Group Title	Chronic Opioid Exposure	Acute Opioid Exposure	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	20	0	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.9 (11.47)	40.9 (11.47)
Sex: Female, Male (Count of Participants)
Female	7 35%	7 Infinity
Male	13 65%	13 Infinity
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN
Asian	3 15%	3 Infinity
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN
Black or African American	3 15%	3 Infinity
White	14 70%	14 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 NaN
Region of Enrollment (participants) [Number]
United States	20 100%	20 Infinity

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Data can not be summarized or included in this table as no data on this measure was collected. 5 CCs of blood were not drawn from any participants at any point in time during the study as the study was terminated due to a lack of resources prior to collection of any study measure data.

Arm/Group Title	Chronic Opioid Exposure	Acute Opioid Exposure
Arm/Group Description	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.	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Laser Doppler Images
Description	The laser doppler is a noninvasive, painless measurement of superficial perfusion that reflects inflammation. Laser doppler images will be taken once per study visit.
Time Frame	Changes in laser doppler images are measured between images taken on Day 1 and Day 30

Outcome Measure Data

Analysis Population Description

Data can not be summarized or included in this table as no data on this measure was collected. Laser doppler image data was not collected from any participants at any point in time during the study as the study was terminated due to a lack of resources prior to collection of any study measure data.

Arm/Group Title	Chronic Opioid Exposure	Acute Opioid Exposure
Arm/Group Description	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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Peltier Device-Heat Pain
Description	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.
Time Frame	Differences in heat pain are assessed between measurements taken on Day 1 and Day 30

Outcome Measure Data

Analysis Population Description

Data can not be summarized or included in this table as no data on this measure was collected. Peltier device-heat pain data was not collected from any participants at any point in time during the study as the study was terminated due to a lack of resources prior to collection of any study measure data.

Arm/Group Title	Chronic Opioid Exposure	Acute Opioid Exposure
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Mechanical Pain Stimuli
Description	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
Time Frame	Changes in mechanical pain stimuli will be assessed between measurements taken on Day 1 and Day 30

Outcome Measure Data

Analysis Population Description

Data can not be summarized or included in this table as no data on this measure was collected. Mechanical pain stimuli data was not collected from any participants at any point in time during the study as the study was terminated due to a lack of resources prior to collection of any study measure data.

Arm/Group Title	Chronic Opioid Exposure	Acute Opioid Exposure
Arm/Group Description	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.	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.
Measure Participants	0	0

Adverse Events

Time Frame	As no data was collected for study measures, no adverse events data was collected.
Adverse Event Reporting Description	There is no difference in definition. As no data was collected for study measures, no adverse events data was collected.
Arm/Group Title	Chronic Opioid Exposure		Acute Opioid Exposure
Arm/Group Description	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.		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.
All Cause Mortality
	Chronic Opioid Exposure		Acute Opioid Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Chronic Opioid Exposure		Acute Opioid Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Chronic Opioid Exposure		Acute Opioid Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

We were unable to analyze any data.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.