Clinical trial NCT02360371: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid Sensitivity
Individual Difference
Abuse Opioids
Keywords: opioid
abuse
genetic
A118G
OPRM1
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2015-02-10
Enrollment: 100
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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)

Primary outcomes:
measure: Self-report Visual Analog Ratings of HIGH
timeFrame: 30 minutes after study drug administration
measure: Self-report Visual Analog Ratings of DRUG EFFECT
timeFrame: 30 minutes after study drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University Bayview Medical Campus
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kelly E Dunn, Ph.D., MBA
role: PRINCIPAL_INVESTIGATOR
References: