Abuse Opioids, Analgesia, Pain
Conditions
Brief summary
The goal of this study is to compare the abuse potential of low-dose equianalgesic buccal buprenorphine to a commonly used full mu opioid receptor (MOR) agonist in a highly controlled experimental setting. This is a translational study in which healthy participants are phenotyped for psychosocial and Opioid-Use-Disorder-risk-related metrics. In a within-subjects crossover design, 60 participants will receive a standard postoperative oral oxycodone dose (10 mg), placebo, and 3 different doses of buccal buprenorphine across 5 separate sessions. Quantitative Sensory Testing (QST) will be used to evaluate alterations in pain responsiveness relative to placebo across buprenorphine doses and oxycodone, and will compare abuse potential (indexed by the standard FDA drug liking metric) following equianalgesic doses of the two drugs.
Interventions
DRUGBuccal Buprenorphine 300 mcg
buprenorphine for 300mcg buccal administration
DRUGBuccal Buprenorphine 600 mcg
buprenorphine for 600mcg buccal administration
DRUGBuccal Buprenorphine 900 mcg
buprenorphine for 900mcg buccal administration. Note: This arm has been discontinued as of 06/25/2024 and has been replaced with the 450mcg buprenorphine buccal administration arm.
DRUGBuccal Placebo
Placebo for buccal administration
DRUGOral Placebo
Placebo for oral administration
DRUGOral immediate-release oxycodone 10mg
Immediate-release oxycodone for 10 mg oral administration
DRUGBuccal Buprenorphine 450mcg
buprenorphine for 450mcg buccal administration. Note: This arm has been added to replace the 900mcg buprenorphine buccal administration arm.
Sponsors
National Institute on Drug Abuse (NIDA)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Intervention model description
randomized, double blind, double-dummy, placebo-controlled, crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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 * Age 18-65 * Opioid-naive status (defined as no use of full mu-opioid receptor (MOR) agonist, partial MOR agonist, or mixed agonist/antagonist medications for the prior 3 months by patient report
Exclusion criteria
* Liver/kidney disease * Chronic pain * Current/prior substance use disorder * Pregnancy (to avoid fetal drug exposure, with pregnancy tests conducted to confirm eligibility) * Seizure disorder * Certain psychiatric conditions (severe depression, bipolar disorder, psychotic disorders) * Recent use of medications that may interfere with study drug metabolism * Recent benzodiazepine or opioid use (confirmed via rapid urine screening prior to each lab session) * The presence of any medical conditions felt by the study physician to render participant unsafe * Prior allergic reaction or intolerance to oxycodone, buprenorphine, or their analogs (explicitly including moderate-to-severe nausea or vomiting with prior opioids) * Recent use of marijuana, delta-8 THC, CBD, and similar products * Recent use of kratom * Severe asthma * Long QT syndrome * Parkinson disease * Weight \<60 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in mean maximum effect score (Emax) of the drug liking visual analog scale (VAS) between oxycodone 10 mg and an equianalgesic dose of buprenorphine | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the drug liking VAS between oxycodone 10 mg and an equianalgesic dose of buprenorphine conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking). |
| Quantitative sensory testing (QST) thermal pain tolerance in seconds | Baseline through 3.5 hours after study drug administration on each medication condition | Mean time in seconds elapsed from onset of the heat pain stimulus to participants withdrawal from the stimulus. Heat pain tolerance is an indicator of pain sensitivity. This will determine the equianalgesic dose of buccal buprenorphine compared to oxycodone 10 mg. Equivalence to oxycodone will be defined as the buprenorphine does that produces a mean thermal pain tolerance increase within 0.5 standard deviation of the oxycodone. response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QST heat pain threshold | Baseline through 3.5 hours after study drug administration on each medication condition | Mean time in seconds elapsed from onset of the thermal stimulus to the point at which heat stimulus is first experienced as painful. Thermal pain threshold is an indicator of pain sensitivity. |
| Visual Analog Scale (VAS) pain intensity | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the pain intensity VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain intensity is a measure of experienced pain intensity on 0 to 100 scale when 0 is no pain and 100 is worst pain imaginable. |
| VAS pain unpleasantness | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the pain unpleasantness VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain unpleasantness is a measure of experienced pain unpleasantness on 0 to 100 scale, when 0 is no unpleasantness and 100 is most unpleasant imaginable. |
| McGill Pain Questionnaire - Short Form | Baseline through 3.5 hours after study drug administration on each medication condition | Mean of maximum McGill Pain Questionnaire - Short Form score between oxycodone 10mg, equianalgesic dose of buprenorphine and placebo. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness. |
| VAS alertness/drowsiness | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS alertness/drowsiness between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS alertness/drowsiness assesses alertness and drowsiness following drug administration on 0 to 100 sale, when 0 is extreme drowsiness, 50 is neutral, and 100 is extreme alertness. |
| VAS any drug effects | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS any drug effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS any drug effects assesses presence of any drug effects felt by participant on 0 to 100 scale, when 0 is no drug effects and 100 is extreme drug effects. |
| Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking). |
| VAS feeling high | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS feeling high between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS feeling high assesses presence of feeling high by participant on 0 to 100 scale when o is not feeling high at all and 100 is feeling extremely high. |
| VAS bad effects | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS bad effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS bad effects assesses presence of drug effects characterized as bad felt by participant on 0 to 100 scale when 0 is no bad drug effects and 100 is extreme bad drug effects. |
| VAS desire to use opioids | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS desire to use opioids between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS desire to use opioids assesses participant's desire to use opioids on a 0-100 scale when 0 is no desire to use opioids and 100 is extreme desire to use opioids. |
| Opioid Adjective Rating Scale | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS Opioid Adjective Rating Scale between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS Opioid Adjective Rating Scale is a 12 item questionnaire which evaluates common sensory and somatic effects of opioid (e.g., itching, vomiting, sweating, nausea, dry mouth). Each effect is rated on 0 to 4 scale when 0 is not at all and 4 is extremely. |
| Temporal summation of pain (TSP) | Baseline through 3.5 hours after study drug administration on each medication condition | Change in pain intensity between first and most painful TSP stimuli (mean of two TSP trials) compared between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo conditions. Pain intensity will be measured on a 0-10 Numeric Rating Scale when when 0 is no pain and 100 is worst pain imaginable. |
| VAS good effects | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean Emax of the VAS good effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS good effects assesses presence of drug effects characterized as good felt by participant on scale 0 to 100 when 0 is no good drug effects and 100 is extreme good drug effects. |
| Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions | Baseline through 3.5 hours after study drug administration on each medication condition | Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking). |
Countries
United States
Contacts
Primary ContactDaniel Larach, MD, MSTR, MA
Backup ContactGail Mayo
Outcome results
None listed