A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Individual Difference; Abuse Opioids; Opioid Sensitivity

Treatments: Drug: Within-subject test of blinded study medication

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02360371

R01DA035246-01A1 (U.S. NIH Grant/Contract)

IRB00047423

Details and patient eligibility

About

Within-subject, double-blind, placebo-controlled examination of opioid abuse potential in healthy individuals as a function of A118G SNP on the OPRM1 gene.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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100 participants in 4 patient groups, including a placebo group

Placebo (oral)

Placebo Comparator group

Description:

Within-subject double-blind, administration of placebo oral capsule. Order of dose randomized session days 3-5.

Treatment:

Drug: Within-subject test of blinded study medication

Hydromorphone (oral) 2mg

Experimental group

Description:

Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.

Treatment:

Drug: Within-subject test of blinded study medication

Hydromorphone (oral) 4mg

Experimental group

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.

Treatment:

Drug: Within-subject test of blinded study medication

Hydromorphone (oral) 8mg

Experimental group

Description:

Within-subject double-blind, administration of hydromorphone via oral capsule. Order of dose randomized session days 3-5.

Treatment:

Drug: Within-subject test of blinded study medication