Back to resultsA118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
Primary Purpose
Opioid Sensitivity, Individual Difference, Abuse Opioids
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Within-subject test of blinded study medication
Sponsored by
About this trial
This is an interventional basic science trial for Opioid Sensitivity focused on measuring opioid, abuse, genetic, A118G, OPRM1
Eligibility Criteria
Inclusion Criterion:
- Provide a urine sample that tests negative for opioids, methadone, buprenorphine, oxycodone, amphetamine, cocaine, and benzodiazepines
- Negative ethanol breath test (0.000)
- Aged 21-50
- Deemed medically eligible to take hydromorphone
Exclusion Criterion:
- Answer "yes" to question 1 of the Brief Pain Inventory (89) to assess the presence of chronic pain.
- Current use of opioids or other medications for pain
- Meet DSM-5 criteria for current or lifetime alcohol or drug use disorder (excluding nicotine)
- Self-report any illicit drug use in the past 7 days
- Self-report opioid use >5 days in the past 30
- Evidence of opioid physical dependence at screening or following 1st residential overnight (following confirmed opioid abstinence)
- Allergy to hydromorphone or other opioid agonists
- Experience an adverse event that warrants opioid antagonist treatment following 1st hydromorphone dose.
- If female, not be pregnant or breastfeeding
- Presence of any clinically significant medical (e.g., chronic renal insufficiency, history of myocardial infarction, seizure disorder) and/or psychiatric illness (e.g., schizophrenia, bipolar disorder) that may interfere with study participation.
- BMI >30 (obese category)
Sites / Locations
- Johns Hopkins University Bayview Medical Campus
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo (oral)
Hydromorphone (oral) 2mg
Hydromorphone (oral) 4mg
Hydromorphone (oral) 8mg
Arm Description
Within-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5.
Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.
Hydromorphone oral capsule administered in double-blind manner on Day 2 as first study drug administration. Hydromorphone 4mg dosing day was set for safety purposes and non-randomized.
Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.
Outcomes
Primary Outcome Measures
Self-report Visual Analog Ratings of HIGH
Peak visual analog rating scale values of HIGH (rated on 0-100 scale with higher scores indicating higher feeling of being HIGH) collected at 30 minute intervals post-drug administration for 6 hours.
Self-report Visual Analog Ratings of DRUG EFFECT
Peak visual analog rating scale values of DRUG EFFECT (rated on 0-100 scale with higher scores indicating higher drug effect) collected at 30 minute intervals post-drug administration for 6 hours.
Secondary Outcome Measures
Full Information
NCT ID
NCT02360371
First Posted
January 29, 2015
Last Updated
September 8, 2021
Sponsor
Johns Hopkins University
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT02360371
Brief Title
A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
Official Title
A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
April 2015 (Actual)
Primary Completion Date
May 2020 (Actual)
Study Completion Date
May 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Within-subject, double-blind, placebo-controlled examination of opioid abuse potential in healthy individuals as a function of A118G SNP on the OPRM1 gene.
Detailed Description
Participants completed a 5-day, within-subject, double-blind, placebo-controlled, randomized, human laboratory abuse potential trial. Healthy individuals were admitted to a residential research unit for 5 consecutive days. Blood samples were drawn for genome wide analyses using the Global Screening Array on day 1. Participants were administered an oral dose of the opioid hydromorphone (4mg) on day 2 of the study. Persons who did not evidence strong agonist effects then proceeded into the randomized period wherein they received 0mg, 2mg, and 8mg of oral hydromorphone on the remaining three study days. The order of dosing was randomized, with only 1 dose administered per day and all participants receiving 1 exposure to each dose. Outcomes were standard human abuse potential metrics, including self-reported drug effects and feeling high. Data were analyzed as a function of the A118SNP on the OPRM1 gene that codes for the mu opioid receptor. The overall aim was to determine whether signal for abuse potential among persons with no history of opioid misuse was associated with genotype.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Sensitivity, Individual Difference, Abuse Opioids
Keywords
opioid, abuse, genetic, A118G, OPRM1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Within-subject, double-blind, randomized, placebo-controlled, human laboratory design wherein each participant completed each of the study conditions (outlined below as four arms). Participants were genotyped for rs-1799971and data were analyzed using between-group designs based upon rs-1799971 status.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Neither participants nor staff were informed of the class of drugs under investigation. Strict blinding was maintained.
Allocation
N/A
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo (oral)
Arm Type
Placebo Comparator
Arm Description
Within-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5.
Arm Title
Hydromorphone (oral) 2mg
Arm Type
Experimental
Arm Description
Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.
Arm Title
Hydromorphone (oral) 4mg
Arm Type
Experimental
Arm Description
Hydromorphone oral capsule administered in double-blind manner on Day 2 as first study drug administration. Hydromorphone 4mg dosing day was set for safety purposes and non-randomized.
Arm Title
Hydromorphone (oral) 8mg
Arm Type
Experimental
Arm Description
Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.
Intervention Type
Drug
Intervention Name(s)
Within-subject test of blinded study medication
Intervention Description
Within-subject double-blind, randomized, placebo-controlled, residential human abuse potential study. All participants received 4mg oral hydromorphone on study day 2 and a subset continued into the randomized portion for study days 3-5 wherein they received placebo, 2mg hydromorphone, and 8mg hydromorphone in randomized order. Only one dose was administered per day and following randomized all participants received each dose in random order. Outcomes were collected during 8-hour residential-based sessions and included metrics of FDA human abuse potential testing as well as secondary outcomes of laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition. Participants were genotyped for rs-1799971 status and results were analyzed as between-group comparisons based upon genotype.
Primary Outcome Measure Information:
Title
Self-report Visual Analog Ratings of HIGH
Description
Peak visual analog rating scale values of HIGH (rated on 0-100 scale with higher scores indicating higher feeling of being HIGH) collected at 30 minute intervals post-drug administration for 6 hours.
Time Frame
30 minutes after study drug administration
Title
Self-report Visual Analog Ratings of DRUG EFFECT
Description
Peak visual analog rating scale values of DRUG EFFECT (rated on 0-100 scale with higher scores indicating higher drug effect) collected at 30 minute intervals post-drug administration for 6 hours.
Time Frame
30 minutes after study drug administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criterion:
Provide a urine sample that tests negative for opioids, methadone, buprenorphine, oxycodone, amphetamine, cocaine, and benzodiazepines
Negative ethanol breath test (0.000)
Aged 21-50
Deemed medically eligible to take hydromorphone
Exclusion Criterion:
Answer "yes" to question 1 of the Brief Pain Inventory (89) to assess the presence of chronic pain.
Current use of opioids or other medications for pain
Meet DSM-5 criteria for current or lifetime alcohol or drug use disorder (excluding nicotine)
Self-report any illicit drug use in the past 7 days
Self-report opioid use >5 days in the past 30
Evidence of opioid physical dependence at screening or following 1st residential overnight (following confirmed opioid abstinence)
Allergy to hydromorphone or other opioid agonists
Experience an adverse event that warrants opioid antagonist treatment following 1st hydromorphone dose.
If female, not be pregnant or breastfeeding
Presence of any clinically significant medical (e.g., chronic renal insufficiency, history of myocardial infarction, seizure disorder) and/or psychiatric illness (e.g., schizophrenia, bipolar disorder) that may interfere with study participation.
BMI >30 (obese category)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly E Dunn, Ph.D., MBA
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University Bayview Medical Campus
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
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