Active Ethanol and Active Iomazenil, Active Ethanol and Placebo Iomazenil, Placebo Ethanol and Active Iomazenil, Placebo Ethanol and Placebo Iomazenil, Alcohol Effect, Driving Under the Influence, Alcohol Impairment
Conditions
Brief summary
Alcohol is abused commonly, but there is no remedy for alcohol intoxication. This project is looking at the substance iomazenil and its effect on alcohol intoxication and alcohol's effects on driving using a driving simulator.
Detailed description
Alcohol is abused commonly, but there is no antidote for alcohol intoxication the way naltrexone or naloxone is an antidote for opioids. A medication that has the potential to block alcohol actions in the Central Nervous System could act as a unique medication in the treatment of alcohol intoxication and alcoholism. This project is evaluating the benzodiazepine partial inverse agonist, iomazenil, as an agent that could reverse alcohol's effects on subjective intoxication, alcohol's effects on driving using a driving simulator and on measures of electrophysiology in the laboratory in healthy subjects.
Interventions
DRUGActive Ethanol
Target BrAC of 0.1% reached over 30 minutes and then clamped to maintain this dose for an additional 60 minutes. This dose is equivalent to consuming approximately 5 drinks. Administered over a total of 90 minutes.
DRUGActive Iomazenil
Active iomazenil, administered intravenously at a dose of 3.7 ug/kg. Administered over 10 minutes, beginning 10 minutes after the start of the ethanol/placebo clamp.
DRUGPlacebo
Control: no alcohol, administered for a total of 90 minutes.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
21 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Males * 21-35 years old * Medically healthy
Exclusion criteria
* Under the age of 21 or greater than the age 35 * History of seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biphasic Ethanol Effects Scale (BAES) | Administered 160 mins and 10 mins prior to the target ethanol/placebo dose being reached, when the target ethanol dose (BrAC of 0.1%)/placebo has been reached, and 15, 70, 90, 150, and 240 minutes after the target ethanol/placebo dose has been reached. | A 14-item scale with 7 items designated to assess stimulant effects associated with the ascending limb of ethanol intoxication and 7 items developed to measure sedative effects associated with the descending limb of ethanol intoxication. The BAES full scale would be 0 to 140. However, the scale itself is analyzed by breaking up the full 14 item scale into 2 parts - sedation and stimulation. Therefore, the total score for sedation ranges from 0 to 70, with higher scores indicating more sedation, and the total score for stimulation also ranges from 0 to 70, with higher scores indicating more stimulation. Timepoints: Administered 160 mins (M160) and 10 mins (M10) prior to the target ethanol/placebo dose being reached, when the target ethanol dose (BrAC of 0.1%)/placebo has been reached (0), and 15 (P15), 70 (P70), 90 (P90), and 150 (P150) minutes after the target ethanol/placebo dose has been reached. |
Countries
United States
Participant flow
Recruitment details
33 participants initiated study procedures beyond screening. Of these 33 participants, 30 completed all four test days (thus receiving all four treatment conditions, one on each of the four test days), 2 participants withdrew from the study after 2 test days (receiving 2 out of the 4 treatment conditions), and 1 participant withdrew after 1 test day (receiving 1 out of the 4 treatment conditions..
Pre-assignment details
Each participant will receive in a randomized, double-blind, cross-over design, ethanol or placebo and iomazenil or placebo. Potential randomizations for each test day: a) active ethanol and placebo iomazenil, b) active ethanol and active iomazenil, c) placebo ethanol and active iomazenil, and d) placebo ethanol and placebo iomazenil
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Participants (N=33) Baseline demographics for all participants that initiated study procedures beyond screening.
Participants will receive in a randomized, double-blind, cross-over design, ethanol or placebo and iomazenil or placebo on each of 4 separate test days. Potential Randomizations for each test day are: a) active ethanol and placebo iomazenil, b) active ethanol and active iomazenil, c) placebo ethanol and active iomazenil, and d) placebo ethanol and placebo iomazenil. A participant who completes all four test days will receive each of the potential randomizations throughout their study participation. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Enrolled Participants (N=33) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants |
| Age, Continuous | 25.76 years STANDARD_DEVIATION 3.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 3 / 30 | 1 / 31 | 3 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 30 | 0 / 31 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Biphasic Ethanol Effects Scale (BAES)
A 14-item scale with 7 items designated to assess stimulant effects associated with the ascending limb of ethanol intoxication and 7 items developed to measure sedative effects associated with the descending limb of ethanol intoxication. The BAES full scale would be 0 to 140. However, the scale itself is analyzed by breaking up the full 14 item scale into 2 parts - sedation and stimulation. Therefore, the total score for sedation ranges from 0 to 70, with higher scores indicating more sedation, and the total score for stimulation also ranges from 0 to 70, with higher scores indicating more stimulation. Timepoints: Administered 160 mins (M160) and 10 mins (M10) prior to the target ethanol/placebo dose being reached, when the target ethanol dose (BrAC of 0.1%)/placebo has been reached (0), and 15 (P15), 70 (P70), 90 (P90), and 150 (P150) minutes after the target ethanol/placebo dose has been reached.
Time frame: Administered 160 mins and 10 mins prior to the target ethanol/placebo dose being reached, when the target ethanol dose (BrAC of 0.1%)/placebo has been reached, and 15, 70, 90, 150, and 240 minutes after the target ethanol/placebo dose has been reached.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P90) | 8.833 score on a scale | Standard Deviation 10.449 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M10) | 12.567 score on a scale | Standard Deviation 12.297 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P70) | 7.2 score on a scale | Standard Deviation 11.075 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M160) | 3.767 score on a scale | Standard Deviation 6.826 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P150) | 8.793 score on a scale | Standard Deviation 11.004 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P90) | 4.9 score on a scale | Standard Deviation 6.088 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P15) | 7 score on a scale | Standard Deviation 7.409 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M10) | 4.767 score on a scale | Standard Deviation 5.74 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint 0) | 13.767 score on a scale | Standard Deviation 12.813 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M160) | 11.2 score on a scale | Standard Deviation 11.152 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P15) | 12.8 score on a scale | Standard Deviation 13.697 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P70) | 9.233 score on a scale | Standard Deviation 11.193 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint 0) | 5.267 score on a scale | Standard Deviation 5.271 |
| Active Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P150) | 2.586 score on a scale | Standard Deviation 4.594 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M160) | 13 score on a scale | Standard Deviation 13.844 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P15) | 5.677 score on a scale | Standard Deviation 7.368 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P150) | 4.567 score on a scale | Standard Deviation 7.257 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P150) | 9.867 score on a scale | Standard Deviation 13.32 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint 0) | 14.484 score on a scale | Standard Deviation 13.466 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P70) | 6.806 score on a scale | Standard Deviation 9.393 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M10) | 4.484 score on a scale | Standard Deviation 6.623 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P70) | 9.839 score on a scale | Standard Deviation 11.827 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint 0) | 5.258 score on a scale | Standard Deviation 6.153 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P90) | 5.677 score on a scale | Standard Deviation 8.89 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P90) | 9.742 score on a scale | Standard Deviation 12.762 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M10) | 12.903 score on a scale | Standard Deviation 11.47 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P15) | 13.968 score on a scale | Standard Deviation 12.875 |
| Active Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M160) | 3.935 score on a scale | Standard Deviation 7.771 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M160) | 3.813 score on a scale | Standard Deviation 7.368 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint 0) | 2.875 score on a scale | Standard Deviation 5.74 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M10) | 3.438 score on a scale | Standard Deviation 5.853 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M10) | 12.188 score on a scale | Standard Deviation 12.678 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint 0) | 10.406 score on a scale | Standard Deviation 12.018 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P15) | 9.625 score on a scale | Standard Deviation 11.187 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P150) | 10.406 score on a scale | Standard Deviation 11.67 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P70) | 10.125 score on a scale | Standard Deviation 11.853 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P15) | 6.75 score on a scale | Standard Deviation 8.74 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P70) | 3.469 score on a scale | Standard Deviation 6.17 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P90) | 2.875 score on a scale | Standard Deviation 6.384 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P90) | 10.094 score on a scale | Standard Deviation 11.217 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P150) | 2.813 score on a scale | Standard Deviation 5.688 |
| Placebo Ethanol and Active Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M160) | 13.281 score on a scale | Standard Deviation 12.606 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P70) | 2.516 score on a scale | Standard Deviation 5.092 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P15) | 3.387 score on a scale | Standard Deviation 6.249 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P70) | 9.903 score on a scale | Standard Deviation 11.324 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P150) | 9.484 score on a scale | Standard Deviation 9.743 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M10) | 3.968 score on a scale | Standard Deviation 7.092 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P150) | 1.548 score on a scale | Standard Deviation 3.897 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint 0) | 8.065 score on a scale | Standard Deviation 9.352 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M10) | 9.129 score on a scale | Standard Deviation 9.57 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P15) | 8.452 score on a scale | Standard Deviation 9.305 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint M160) | 12.387 score on a scale | Standard Deviation 11.292 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint M160) | 3.194 score on a scale | Standard Deviation 5.431 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint P90) | 1.452 score on a scale | Standard Deviation 3.491 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Sedation Effects (Timepoint 0) | 3.452 score on a scale | Standard Deviation 6.35 |
| Placebo Ethanol and Placebo Iomazenil | Biphasic Ethanol Effects Scale (BAES) | Stimulation Effects (Timepoint P90) | 9.71 score on a scale | Standard Deviation 11.261 |