A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-30

Study Completion Date

2021-05-31

Brief Summary

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

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Detailed Description

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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

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Opioid Sensitivity Individual Difference Abuse Opioids

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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 Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Neither participants nor staff were informed of the class of drugs under investigation. Strict blinding was maintained.

Study Groups

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Placebo (oral)

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

Group Type PLACEBO_COMPARATOR

Within-subject test of blinded study medication

Intervention Type 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

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

Group Type EXPERIMENTAL

Within-subject test of blinded study medication

Intervention Type 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) 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.

Group Type EXPERIMENTAL

Within-subject test of blinded study medication

Intervention Type 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) 8mg

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

Group Type EXPERIMENTAL

Within-subject test of blinded study medication

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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)

Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes