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| ID | Type | Description | Link |
|---|---|---|---|
| R01DA050334 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adults with chronic non-cancer low back pain | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | In randomized order (crossover) across 3 laboratory sessions, participants will undergo laboratory evoked thermal pain response testing with: 1) 0.13 mg/kg of oral oxycodone (in 1mg/ml syrup) plus 20ml i.v. saline placebo, 2) 8mg of i.v. naloxone (in 20ml saline vehicle) plus oral placebo syrup (quantity matching oxycodone syrup volume), or 3) 20ml i.v. saline placebo plus oral placebo syrup (quantity matching oxycodone syrup volume). Thermal pain testing utilizes a Medoc TSAII NeuroSensory Analyzer. This equipment is used to assess heat pain threshold and tolerance using an ascending method of limits protocol. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition | Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition (across 2 testing days). The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive change values indicate decreased pain responsiveness post intervention. | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean DELTA Drug Liking subscale scores in the oxycodone condition | Mean DELTA Drug Liking subscale scores in the oxycodone condition. The DELTA Drug Liking subscale consists of a single item asking about overall perceived drug liking. The 1-5 scale is anchored with 1 representing dislike a lot and 5 representing like a lot. | One 1 laboratory assessment day |
| 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) | 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). More negative standardized values will indicate low levels of endogenous pain inhibition and more positive levels will indicate high levels of endogenous pain inhibition. | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean changes in MPQ-2 ratings of ischemic task pain from the placebo to oxycodone condition | Mean within participant changes in MPQ-2 ratings of ischemic task pain from the placebo to oxycodone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive change values indicate decreased pain responsiveness. | Across 2 laboratory assessment days (an expected average of 15 day period) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stephen Bruehl, PhD | Contact | 615-936-1821 | stephen.bruehl@vumc.org | |
| Gail Mayo | Contact | 615-936-1705 | gail.mayo@vumc.org |
| Name | Affiliation | Role |
|---|---|---|
| Stephen Bruehl, PhD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37212 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16554396 | Background | al'Absi M, France C, Harju A, France J, Wittmers L. Adrenocortical and nociceptive responses to opioid blockade in hypertension-prone men and women. Psychosom Med. 2006 Mar-Apr;68(2):292-8. doi: 10.1097/01.psy.0000203240.64965.bd. | |
| 26374993 | Background | Altun A, Ozdemir E, Yildirim K, Gursoy S, Durmus N, Bagcivan I. The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. Gen Physiol Biophys. 2015 Oct;34(4):433-40. doi: 10.4149/gpb_2015017. |
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No plan to make individual participant data (IPD) available to other researchers.
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| D001416 | Back Pain |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D010098 | Oxycodone |
| D009270 | Naloxone |
| ID | Term |
|---|---|
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
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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).
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The participant and investigator will be blinded to the drug order across the 3 laboratory drug administration sessions.
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|
|
| Oxycodone | Drug | In randomized order (crossover) across 3 laboratory sessions, participants will undergo laboratory evoked thermal pain response testing with: 1) 0.13 mg/kg of oral oxycodone (in 1mg/ml syrup) plus 20ml i.v. saline placebo, 2) 8mg of i.v. naloxone (in 20ml saline vehicle) plus oral placebo syrup (quantity matching oxycodone syrup volume), or 3) 20ml i.v. saline placebo plus oral placebo syrup (quantity matching oxycodone syrup volume). Thermal pain testing utilizes a Medoc TSAII NeuroSensory Analyzer. This equipment is used to assess heat pain threshold and tolerance using an ascending method of limits protocol. |
|
| Naloxone | Drug | In randomized order (crossover) across 3 laboratory sessions, participants will undergo laboratory evoked thermal pain response testing with: 1) 0.13 mg/kg of oral oxycodone (in 1mg/ml syrup) plus 20ml i.v. saline placebo, 2) 8mg of i.v. naloxone (in 20ml saline vehicle) plus oral placebo syrup (quantity matching oxycodone syrup volume), or 3) 20ml i.v. saline placebo plus oral placebo syrup (quantity matching oxycodone syrup volume). Thermal pain testing utilizes a Medoc TSAII NeuroSensory Analyzer. This equipment is used to assess heat pain threshold and tolerance using an ascending method of limits protocol. |
|
|
| Mean changes in Visual Analog Scale (VAS) intensity ratings of ischemic task pain from the placebo to oxycodone condition | Mean within participant changes in VAS intensity ratings of ischemic task pain from the placebo to oxycodone condition. The score is a rating of current acute pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain") | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean changes in MPQ-2 ratings of heat task pain from the placebo to oxycodone condition | Mean within participant changes in MPQ-2 ratings of heat task pain from the placebo to oxycodone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive change values indicate decreased pain responsiveness. | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean changes in VAS intensity ratings of heat task pain from the placebo to oxycodone condition | Mean within participant changes in VAS intensity ratings of heat task pain from the placebo to oxycodone condition. The score is a rating of current acute pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain") | Across 2 laboratory assessment days (an expected average of 15 day period) |
| DELTA Take Again subscale scores in the oxycodone condition | Mean oxycodone condition Take Again (DELTA subscale) score. The score ranges from 1-5 where 1 represents definitely would not and 5 represents definitely would. Positive values indicate decreased overall drug effects post intervention. | 1 laboratory assessment day (an expected average of 15 day period) |
| Mean Delta Effects subscale in the oxycodone condition | Mean oxycodone condition Effects (DELTA) -Drug Effect subscale ratings. The score ranges from 1-5 where 1 represents no effect and 5 represents very strong effect. Positive values indicate decreased overall drug effects post intervention. | 1 laboratory assessment day (an expected average of 15 day period) |
| Mean VAS Opioid Euphoria subscale in the oxycodone condition | Mean oxycodone condition VAS Opioid Effects-Euphoria subscale ratings. The score ranges from 0-300 where 0 means no euphoria and 300 means most euphoria possible. Positive values indicate greater euphoria. | 1 laboratory assessment day (an expected average of 15 day period) |
| Mean VAS Opioid Unpleasantness subscale in the oxycodone condition | Mean oxycodone condition VAS Opioid Effects-Unpleasantness subscale ratings. The score ranges from 0-300 where 0 means no unpleasantness and 300 means the most unpleasantness possible. Positive values indicate greater perceived unpleasantness. | 1 laboratory assessment day (an expected average of 15 day period) |
| Mean VAS Opioid Sedation subscale in the oxycodone condition | Mean oxycodone condition VAS Opioid Effects-Sedation subscale ratings. The score ranges from 0-300 where 0 means no sedation and 300 means the most sedation possible. Positive values indicate greater sedation. | 1 laboratory assessment day (an expected average of 15 day period) |
| Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to naloxone condition | Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to naloxone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents the most intense pain. Positive change values indicate greater endogenous opioid pain inhibition . | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of ischemic task pain from the placebo to naloxone condition | Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of ischemic task pain from the placebo to naloxone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents the most intense pain. Positive change values indicate greater endogenous opioid pain inhibition. | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean changes in VAS intensity ratings of ischemic task pain from the placebo to naloxone condition | Mean within participant changes in VAS intensity ratings of ischemic task pain from the placebo to naloxone condition. The VAS score is a rating of ischemic task pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain"). Positive change values indicate greater endogenous opioid pain inhibition. | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of heat task pain from the placebo to naloxone condition | Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of heat task pain from the placebo to naloxone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents the most intense pain. Positive change values indicate greater endogenous opioid pain inhibition | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean changes in VAS intensity ratings of heat task pain from the placebo to naloxone condition | Mean within participant changes in VAS intensity ratings of thermal task pain from the placebo to naloxone condition. The VAS score is a rating of ischemic task pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain"). Positive change values indicate greater endogenous opioid pain inhibition. | Across 2 laboratory assessment days (an expected average of 15 day period) |
| Mean plasma levels of endocannabinoids | Mean plasma levels of endocannabinoids | Across 3 laboratory assessment days (an expected average of 15 day period) |
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| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |