Pain, Opioids and Pro-Inflammatory Immune Responses

Immunologic Activity Alteration Clinical Trial

Official title:

Pain, Opioids and Pro-Inflammatory Immune Responses

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01210066
• Other study ID #: 5R21DA027558
• Status: Terminated
• Phase: Phase 1
• First received: September 27, 2010
• Last updated: December 27, 2016
• Start date: July 2010
• Est. completion date: May 2012

Study information

• Verified date: December 2016
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Providing pain management to the patient who abuses prescription opioids presents a clinical challenge, not only due to concerns about "drug-seeking", but because they have increased sensitivity to pain, a phenomenon identified as opioid-induced hyperalgesia (OIH). In an effort to improve pain treatment, the aims of the proposed work are to evaluate the analgesic and hyperalgesic effects of opioids to acute pain in this vulnerable population, and to examine the role of opioid-induced proinflammatory changes in these responses.

Description:

Both acute pain and opioid administration have been shown to induce a systemic pro-inflammatory response. However, the presence of these inflammatory responses is unknown in situations where a co-occurrence of pain and opioid administration exists as is the common clinical case of a patient with acute pain and taking opioid analgesics. A patient population for whom the combined effects of pain and opioids on immune function are particularly complex are the estimated 5.2 million Americans aged 12 or older who abuse prescription opioids. Not only are these individuals at risk for poor pain management due to their status as an "addict", but there is good preclinical evidence to suggest that their chronic opioid use brings with it a general state of systemic inflammation, and thus setting the patient up for a unique or enhanced inflammatory response to the combination of acute opioids and pain. To better understand the health implications of treating acute pain with opioids in patients and in particular, those who abuse prescription opioids, inflammatory responses to the main and interaction effects of acute pain and opioid administration will be examined in well-characterized samples of each. Specifically, we will evaluate the inflammatory and cytokine responses to: (1) experimental pain; (2) an acute opioid challenge; and (3) the combination of opioid administration followed by cold-pressor pain, in healthy control subjects and age- and gender-matched prescription opioid abusers.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 40 Years

Eligibility

Inclusion criteria:

• male and non-pregnant female, non-smoking adults in good general health

• between the ages of 21-40 years old

• fluent in English with willingness to participate in the research study

Supplementary Inclusion Criteria: Prescription Opioid Abusers

• DSM-IVR diagnosis of prescription opioid abuse or dependence disorder

• compliance in treatment and on a stable dose of buprenorphine (6-24mg/day) x at least 10 days prior to screening

• Participation in an ISAP treatment program or a qualified community-based opioid treatment program or private clinic for the entire duration of their study participation

Exclusion criteria:

• regular use of any medication that influences immune status or immune system function

• regular use of a medication that influences pain perception, including opioids (* only for healthy subjects population*)

• Regular use of a medication that influences pain perception, except for buprenorphine (** only for POA population**)

• known hypersensitivity to opioids or no previous opioid exposure (*only healthy controls)

• presence of acute or chronic pain syndrome

• neuropsychiatric illness (i.e., peripheral neuropathy, schizophrenia) known to affect pain perception

• presence of chronic immune compromise (hepatitis C, HIV) or acute infection within the last four weeks

• current or past history of high blood pressure, heart disease, or stroke, or currently have a pacemaker.

• current DSM-IV diagnosis

• BMI less than 18.5 or greater than 29.9

• History of sleep apnea

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Immunologic Activity Alteration
• Pro-inflammatory Activity

Intervention

Drug:
• Fentanyl
IV fentanyl 1mcg/kg

Other:
• Cold pressor test
Non-dominant arm submerged in ice water (0 degrees Celsius) until it is no longer tolerable but less than 5 minutes
• Fentanyl plus cold pressor test
fentanyl IV 1mcg/kg fifteen minutes prior to cold pressor test (arm submerged in ice water until no longer tolerable but no longer than 5 minutes)

Locations

Country	Name	City	State
United States	UCLA School of Nursing	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (1)

Compton P, Griffis C, Breen EC, Torrington M, Sadakane R, Tefera E, Irwin MR. Opioid treatment of experimental pain activates nuclear factor-?B. J Opioid Manag. 2015 Mar-Apr;11(2):115-25. doi: 10.5055/jom.2015.0261. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma levels of pro-inflammatory cytokine IL-6	inflammatory cytokine activity will be evaluated with an in vivo approach over a three hour period of time to enable observation of the duration of opioid activity	15 minutes prior to fentanyl administration, 60 and 180 minutes post fentanyl administration,	No