Opioid SensitivityPhase 2NCT02360371
A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
A Phase 2 study testing Within-subject test of blinded study medication in people with Opioid Sensitivity and Individual Difference, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Opioid Sensitivity, Individual Difference, Abuse Opioids
- What is being tested?
- Within-subject test of blinded study medication
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University Bayview Medical Campus
Baltimore, Maryland, 21224
About this study
Within-subject, double-blind, placebo-controlled examination of opioid abuse potential in healthy individuals as a function of A118G SNP on the OPRM1 gene.
Read the 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.
- Conditions
- Opioid Sensitivity, Individual Difference, Abuse Opioids
- Being tested
- Within-subject test of blinded study medication
- Keywords
- opioid, abuse, genetic, A118G, OPRM1
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Within-subject test of blinded study medicationDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo (oral) | Placebo comparator | Within-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5. Receives: Drug: Within-subject test of blinded study medication |
| Hydromorphone (oral) 2mg | Experimental | Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5. Receives: Drug: Within-subject test of blinded study medication |
| Hydromorphone (oral) 4mg | Experimental | 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. Receives: Drug: Within-subject test of blinded study medication |
| Hydromorphone (oral) 8mg | Experimental | Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5. Receives: Drug: Within-subject test of blinded study medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 minutes after study drug administration
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.
Measured: 30 minutes after study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study startApr 2015
- Primary completionMay 2020
- Study completionMay 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid SensitivityStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Kelly E Dunn, Ph.D., MBA, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02360371
- Sponsor's protocol ID
- IRB00047423
- Other IDs
- R01DA035246-01A1
- Status last verified
- Feb 2025
- First submitted
- 29 Jan 2015
- Last updated
- 27 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dunn KE, Huhn AS, Finan PH, Mange A, Bergeria CL, Maher BS, Rabinowitz JA, Strain EC, Antoine D. Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment. Addict Biol. 2024 Jan;29(1):e13355. doi: 10.1111/adb.13355.
PubMed 38221808
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
- ClinicalTrials.gov ID
- NCT02360371
- Acronym / sponsor ID
- IRB00047423
- Conditions
- Opioid Sensitivity, Individual Difference, Abuse Opioids
- Keywords
- opioid, abuse, genetic, A118G, OPRM1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Apr 2015 (actual)
- Primary completion
- May 2020 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Posted 5 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo (oral) | Placebo comparator | Drug: Within-subject test of blinded study medicationWithin-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5. |
| Hydromorphone (oral) 2mg | Experimental | Drug: Within-subject test of blinded study medicationWithin-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5. |
| Hydromorphone (oral) 4mg | Experimental | Drug: Within-subject test of blinded study medicationHydromorphone 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. |
| Hydromorphone (oral) 8mg | Experimental | Drug: Within-subject test of blinded study medicationWithin-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Within-subject test of blinded study medicationWithin-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. | Drug | Hydromorphone (oral) 2mg, Hydromorphone (oral) 4mg, Hydromorphone (oral) 8mg, Placebo (oral) |
Primary outcome
Self-report Visual Analog Ratings of HIGH
Time frame: 30 minutes after study drug administration
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
Time frame: 30 minutes after study drug administration
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38221808Dunn KE, Huhn AS, Finan PH, Mange A, Bergeria CL, Maher BS, Rabinowitz JA, Strain EC, Antoine D. Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment. Addict Biol. 2024 Jan;29(1):e13355. doi: 10.1111/adb.13355.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kelly E Dunn, Ph.D., MBA principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Within-subject test of blinded study medication in people with Opioid Sensitivity and Individual Difference, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-report Visual Analog Ratings of HIGH (time frame: 30 minutes after study drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02360371, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.