A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans

NCT02360371 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00047423R01DA035246-01A1
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Sensitivity; Individual Difference; Abuse Opioids

Keywords

opioid; abuse; genetic; A118G; OPRM1

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  30 minutes after study drug administration

Study Arms (4)

Placebo (oral)

PLACEBO COMPARATOR

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

Hydromorphone (oral) 2mg

EXPERIMENTAL

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

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.

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.

Drug: Within-subject test of blinded study medication

Interventions

Within-subject test of blinded study medication DRUG

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.

Hydromorphone (oral) 2mg; Hydromorphone (oral) 4mg; Hydromorphone (oral) 8mg; Placebo (oral)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Johns Hopkins University Bayview Medical Campus

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• 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.

  PMID: 38221808 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Kelly Dunn, Ph.D., MBA
• Organization: Johns Hopkins University School of Medicine

kdunn9@jhmi.edu

410-550-2254

Study Officials

• Kelly E Dunn, Ph.D., MBA

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Neither participants nor staff were informed of the class of drugs under investigation. Strict blinding was maintained.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 10, 2015
• Study Start: April 1, 2015
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2021
• Last Updated: February 27, 2025
• Results First Posted: October 5, 2021

Record last verified: 2025-02

Locations

US (1)