Clinical trial NCT05142267: Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms
Official title: Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Opioid Use Disorder
Back Pain
Stress
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2021-12-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study will be a mixed between/within-subjects design with double-blind counterbalanced placebo-controlled administration of both an opioid antagonist and an opioid agonist. Both drugs are being administered solely to probe mechanisms linking stress with individual differences in opioid analgesic responses (this is not an efficacy trial).
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to see how stress influences the effects of opioid pain medications often used to help relieve back pain. The study will help to learn more about how high stress levels could increase risk for pain medication misuse.

Detailed description: The purpose of this project is to advance mechanistic knowledge of how stress impacts differential opioid analgesic responses that enhance risk for opioid use disorder (OUD), potentially informing development of data-driven precision pain medicine algorithms to mitigate opioid related risks.

The study aims to determine whether subjective and physiological stress-related measures are associated with analgesic and misuse-relevant subjective responses to placebo-controlled oxycodone administration. The study also aims to evaluate associations between stress-related measures and both endogenous opioid (EO) function and endocannabinoid (EC) levels and to test whether EO and EC mechanisms contribute to associations between stress-related measures and oxycodone responses

Using a mixed between/within-subject design, the study will obtain baseline assessment of stress related markers followed by 3 laboratory sessions with assessment of endocannabinoids, back pain assessment, and exposure to standardized evoked pain stimuli after administration of placebo, naloxone, and oxycodone.

Eligibility criteria: Inclusion Criteria:

* Intact cognitive status and ability to provide informed consent
* Ability to read and write in English sufficiently to understand and complete study questionnaires (which are only validated in English)
* Age 18 or older And
* Presence of persistent daily low back pain of at least three months duration and of at least a 3/10 in average intensity

Exclusion Criteria:

* History of renal or hepatic dysfunction
* Reports of current or past alcohol or substance abuse or treatment for such condition
* A reported history of PTSD, psychotic, or bipolar disorders
* Chronic pain due to malignancy (e.g., cancer) or autoimmune disorders (e.g., rheumatoid arthritis, lupus)
* Reports of recent benzodiazepine use (confirmed via rapid urine screening prior to each lab session)
* Any medical conditions (e.g., significant cardiovascular disease) that the study physician feels would contraindicate participation in the lab stressors
* Reported daily opiate use within the past 6 months, or use of any opioid analgesic medications within 3 days of study participation (confirmed through rapid urine screening prior to each lab session)
* Pregnancy (females only, to avoid fetal drug exposure - pregnancy tests conducted prior to each lab session to confirm eligibility)
* Prior allergic reaction/intolerance to oxycodone or its analogs

Primary outcomes:
measure: Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean DELTA Drug Liking subscale scores in the oxycodone condition
timeFrame: One 1 laboratory assessment day
measure: Composite measure of changes in MPQ-2 ratings of low back pain from the placebo to naloxone condition (standardized) plus plasma levels of endocannabinoids (standardized)
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary outcomes:
measure: Mean changes in MPQ-2 ratings of ischemic task pain from the placebo to oxycodone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean changes in Visual Analog Scale (VAS) intensity ratings of ischemic task pain from the placebo to oxycodone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean changes in MPQ-2 ratings of heat task pain from the placebo to oxycodone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean changes in VAS intensity ratings of heat task pain from the placebo to oxycodone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: DELTA Take Again subscale scores in the oxycodone condition
timeFrame: 1 laboratory assessment day (an expected average of 15 day period)
measure: Mean Delta Effects subscale in the oxycodone condition
timeFrame: 1 laboratory assessment day (an expected average of 15 day period)
measure: Mean VAS Opioid Euphoria subscale in the oxycodone condition
timeFrame: 1 laboratory assessment day (an expected average of 15 day period)
measure: Mean VAS Opioid Unpleasantness subscale in the oxycodone condition
timeFrame: 1 laboratory assessment day (an expected average of 15 day period)
measure: Mean VAS Opioid Sedation subscale in the oxycodone condition
timeFrame: 1 laboratory assessment day (an expected average of 15 day period)
measure: Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to naloxone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of ischemic task pain from the placebo to naloxone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean changes in VAS intensity ratings of ischemic task pain from the placebo to naloxone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of heat task pain from the placebo to naloxone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean changes in VAS intensity ratings of heat task pain from the placebo to naloxone condition
timeFrame: Across 2 laboratory assessment days (an expected average of 15 day period)
measure: Mean plasma levels of endocannabinoids
timeFrame: Across 3 laboratory assessment days (an expected average of 15 day period)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Stephen Bruehl, PhD
role: PRINCIPAL_INVESTIGATOR
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