A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans

• ClinicalTrials.gov Identifier: NCT02360371
• Recruitment Status: Completed
• First Posted: February 10, 2015
• Results First Posted: October 5, 2021
• Last Update Posted: October 5, 2021
• Sponsor: Johns Hopkins University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Johns Hopkins University

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.

Condition or disease	Intervention/treatment	Phase
Opioid Sensitivity; Individual Difference; Abuse Opioids	Drug: Within-subject test of blinded study medication	Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Neither participants nor staff were informed of the class of drugs under investigation. Strict blinding was maintained.
• Primary Purpose: Basic Science
• Official Title: A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: May 2020
• Actual Study Completion Date: May 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo (oral); Within-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5.	Drug: Within-subject test of blinded study medication; 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.
Experimental: Hydromorphone (oral) 2mg; Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.	Drug: Within-subject test of blinded study medication; 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.
Experimental: Hydromorphone (oral) 4mg; 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.	Drug: Within-subject test of blinded study medication; 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.
Experimental: Hydromorphone (oral) 8mg; Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.	Drug: Within-subject test of blinded study medication; 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.

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criterion:

1. Provide a urine sample that tests negative for opioids, methadone, buprenorphine, oxycodone, amphetamine, cocaine, and benzodiazepines
2. Negative ethanol breath test (0.000)
3. Aged 21-50
4. Deemed medically eligible to take hydromorphone

Exclusion Criterion:

1. Answer "yes" to question 1 of the Brief Pain Inventory (89) to assess the presence of chronic pain.
2. Current use of opioids or other medications for pain
3. Meet DSM-5 criteria for current or lifetime alcohol or drug use disorder (excluding nicotine)
4. Self-report any illicit drug use in the past 7 days
5. Self-report opioid use >5 days in the past 30
6. Evidence of opioid physical dependence at screening or following 1st residential overnight (following confirmed opioid abstinence)
7. Allergy to hydromorphone or other opioid agonists
8. Experience an adverse event that warrants opioid antagonist treatment following 1st hydromorphone dose.
9. If female, not be pregnant or breastfeeding
10. 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.
11. BMI >30 (obese category)

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University Bayview Medical Campus

Baltimore, Maryland, United States, 21224

Sponsors and Collaborators

Johns Hopkins University

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Kelly E Dunn, Ph.D., MBA; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] October 16, 2019

Informed Consent Form  [PDF] October 29, 2019

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02360371
• Other Study ID Numbers: IRB00047423; R01DA035246-01A1 ( U.S. NIH Grant/Contract )
• First Posted: February 10, 2015
• Results First Posted: October 5, 2021
• Last Update Posted: October 5, 2021
• Last Verified: September 2021

Keywords provided by Johns Hopkins University:

opioid; abuse; genetic; A118G; OPRM1

Additional relevant MeSH terms:

Hypersensitivity; Immune System Diseases