A Phase 1/2 interventional study of Perampanel and Placebo in Alcoholism, sponsored by Virginia Commonwealth University. Completed at 4 sites in United States. Open to participants aged 21 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-08-18.
Sponsored by Virginia Commonwealth University · Phase 1/2, Interventional, and Treatment
The purpose of this study is to determine whether perampanel alters the response to alcohol for heavy drinkers. It is hypothesized that perampanel will reduce the rewarding and reinforcing properties of alcohol in the laboratory setting.
The main goal of the proposed study is to determine whether the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPA-R) antagonist perampanel alters the response to ethanol (i.e., the rewarding and reinforcing effects) using a validated laboratory paradigm of intravenous (IV) ethanol infusion. Fifty non-treatment seeking heavy drinkers (NTSHDs), N=50, and twenty-five social drinkers (N=25) will undergo three test days each: once after receiving a placebo medication, once after receiving moderate dose perampanel, and once after receiving a higher dose of perampanel. This experiment is the first step in a series of expedient studies that will rapidly determine perampanel's potential as a treatment for alcohol dependence. If findings show perampanel reduces the rewarding and reinforcing properties of alcohol in the laboratory setting (in humans), it would provide a strong rationale for clinical treatment trials with this medication. This approach is innovative because it tests a highly novel AMPA-R antagonist for the treatment of alcoholism, and uses a state-of-the-art computer assisted IV alcohol pump infusion system (called CAIS) to reduce variability in blood alcohol concentrations, thus improving the data quality.
1,606 studies on the registry are indexed under Alcoholism; 328 are open to participants now.
This study's enrollment of 22 is below the median of 87 across 1,371 interventional studies indexed under Alcoholism.
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Exclusion Criteria:
Participants will have 3 test days each, 2 weeks apart, in a randomized order, following either pretreatment with daily perampanel 2mg days prior to each test day, and then observed dosing moderate 6mg dose perampanel in the lab 1 hour before a one-time alcohol infusion . Each lab session occurs exactly a week after starting the medication for that round. The wash out period between lab test session phases will be 7-10 days. Subjects will receive 2 days of 2mg perampanel after each lab to taper down (included in the washout period). The next appointment will be brief at the start of the next phase, at which point the next week of low dose perampanel or placebo will be started. With the washout period and the 7 day taper of the next phase, the actual lab sessions will occur 14-17 days apart. All test days will involve administration of alcohol with the same 3 target doses \[target Breath Alcohol Concentration (BrAc) =20mg%, 60mg%, and 100mg%\] in a step-wise fashion.
Drug: Perampanel
Participants will have 3 test days each, 2 weeks apart, in a randomized order, following either pretreatment with placebo 7 days prior to each test day, and then observed dosing of placebo in the lab 1 hour before a one-time alcohol infusion . Each lab session occurs exactly a week after starting the medication for that round. The wash out period between lab test session phases will be 7-10 days. Subjects will receive 2 days of 2mg perampanel after each lab to taper down (included in the washout period). The next appointment will be brief at the start of the next phase, at which point the next week of low dose perampanel or placebo will be started. With the washout period and the 7 day taper of the next phase, the actual lab sessions will occur 14-17 days apart. All test days will involve administration of alcohol with the same 3 target doses \[target Breath Alcohol Concentration (BrAc) =20mg%, 60mg%, and 100mg%\] in a step-wise fashion.
Drug: Placebo
Participants will have 3 test days each, 2 weeks apart, in a randomized order, following either pretreatment with daily perampanel 2mg 7 days prior to each test day, and then observed dosing of high dose perampanel (10mg) in the lab 1 hour before a one-time alcohol infusion . Each lab session occurs exactly a week after starting the medication for that round. The wash out period between lab test session phases will be 7-10 days. Subjects will receive 2 days of 2mg perampanel after each lab to taper down (included in the washout period). The next appointment will be brief at the start of the next phase, at which point the next week of low dose perampanel or placebo will be started. With the washout period and the 7 day taper of the next phase, the actual lab sessions will occur 14-17 days apart. All test days will involve administration of alcohol with the same 3 target doses \[target Breath Alcohol Concentration (BrAc) =20mg%, 60mg%, and 100mg%\] in a step-wise fashion.
Drug: Perampanel
Perampanel is a noncompetitive (allosteric) antagonist of the AMPA-R that is well-absorbed (100% bioavailability), has good blood-brain-barrier penetration, and rapidly reaches peak plasma concentrations (1 hour). To date, there have been no clinical trials of AMPA-R antagonists (e.g., perampanel) for the treatment of alcoholism.
Also known as: AMPA-R antagonist, anticonvulsant
Placebo given in place of perampanel during the pre-treatment period and lab session days.
Biphasic Alcohol Effects Scale (BAES): Stimulant Subscale
A 14-item scale with 7 items designed to assess stimulant effects from alcohol intoxication and 7 items developed to measure the sedative effects of alcohol. This scale was selected as a primary outcome measure because it is sensitive to the effect of alcohol. This outcome item reports the Stimulant Subscale results analyzed with mixed models. Each item can be scored a minimum of zero (0) or up to 10 with the 10 representing feeling more or the most intoxicated in that item's description (e.g., "excited"). The minimum score is 0 and the maximum score is 70. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
Time frame: 98 minutes
Biphasic Alcohol Effects Scale (BAES)- Sedative Subscale
A 14-item scale with 7 items designed to assess stimulant effects from alcohol intoxication and 7 items developed to measure the sedative effects of alcohol. This scale was selected as a primary outcome measure because it is sensitive to the effect of alcohol. This entry item show the results for the sedative subscale evaluated in mixed models. Each item can be scored a minimum of zero (0) or up to 10 with the 10 representing feeling more or the most intoxicated in that item's description (e.g., "sedated"). The minimum score is 0 and the maximum score is 70. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
Time frame: 98 minutes
Drug Effects Questionaire (DEQ)
consists of four items that measure current alcohol effects: 'feel alcohol', 'feel high', 'like alcohol', and 'want more alcohol'. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes). There are five items on the scale with scores of 0 to 100, and the total score is used by averaging all five items, thus, the minimum total score on the scale is 0 and the maximum is 100. The lowest score 0 represents "not at all" or not experiencing any drug effects from alcohol, and 100 represents "extremely" experiencing alcohol effects.
Time frame: 98 min
Alcohol Urge Questionnaire (AUQ)
A valid eight-item Likert-type scale designed to assess acute alcohol craving. Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. A total score is computed by averaging the item scores. Higher scores reflect greater craving. The minimum score is 7, and the maximum is 49. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
Time frame: 98 min
Side Effect Questionnaire (SEQ)
This consists of a list of side effects associated with perampanel (e.g., fatigue, dizziness), rated from 0="none" to 4="severe". The mean for each subject across all items is included in each group/arm mean. The lowest score on the scale would be 0 and the maximum 4, as the mean across items is taken and not a sum. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
Time frame: 98 minutes
Profile of Mood States (POMS) 2 Short Version Total Score
The Profile of Mood States (POMS) 2 short version contains a subset of 35 items from the full-length versions. This subset comprises those five items on full version POMS scale that exhibited good item-total correlations and best predicted their respective scale scores, this is a TOTAL score Representing total mood disturbance. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes). The minimum is 0 and the maximum is 100 with higher numbers indicating greater mood disturbance.
Time frame: 98 minutes
| Milestone | Placebo, Then Perampanel 6mg, Then Perampanel 10mg | Placebo, Then Perampanel 10mg, Then Perampanel 6mg | Perampanel 6mg, Then Placebo, Then Perampanel 10mg | Perampanel 6mg, Then Perampanel 10mg, Then Placebo | Perampanel 10mg, Then Perampanel 6mg, Then Placebo | Perampanel 10mg, Then Placebo, Then Perampanel 6mg |
|---|---|---|---|---|---|---|
| Started | 4 | 4 | 5 | 4 | 3 | 2 |
| Completed | 4 | 4 | 3 | 0 | 3 | 0 |
| Not completed | 0 | 0 | 2 | 4 | 0 | 2 |
| Withdrew: Withdrawal by subject | 0 | 0 | 2 | 4 | 0 | 2 |
A 14-item scale with 7 items designed to assess stimulant effects from alcohol intoxication and 7 items developed to measure the sedative effects of alcohol. This scale was selected as a primary outcome measure because it is sensitive to the effect of alcohol. This outcome item reports the Stimulant Subscale results analyzed with mixed models. Each item can be scored a minimum of zero (0) or up to 10 with the 10 representing feeling more or the most intoxicated in that item's description (e.g., "excited"). The minimum score is 0 and the maximum score is 70. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
| score on a scale | Placebo Medication Dose | Perampanel 6mg Dose | Perampanel 10mg Dose |
|---|---|---|---|
| Biphasic Alcohol Effects Scale (BAES): Stimulant Subscale | 13.756 ± 2.747 | 14.053 ± 2.658 | 13.026 ± 2.816 |
A 14-item scale with 7 items designed to assess stimulant effects from alcohol intoxication and 7 items developed to measure the sedative effects of alcohol. This scale was selected as a primary outcome measure because it is sensitive to the effect of alcohol. This entry item show the results for the sedative subscale evaluated in mixed models. Each item can be scored a minimum of zero (0) or up to 10 with the 10 representing feeling more or the most intoxicated in that item's description (e.g., "sedated"). The minimum score is 0 and the maximum score is 70. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
| score on a scale | Placebo | Perampanel 6mg | Perampanel 10 mg |
|---|---|---|---|
| Biphasic Alcohol Effects Scale (BAES)- Sedative Subscale | 4.624 ± 1.784 | 7.159 ± 1.649 | 10.263 ± 1.797 |
consists of four items that measure current alcohol effects: 'feel alcohol', 'feel high', 'like alcohol', and 'want more alcohol'. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes). There are five items on the scale with scores of 0 to 100, and the total score is used by averaging all five items, thus, the minimum total score on the scale is 0 and the maximum is 100. The lowest score 0 represents "not at all" or not experiencing any drug effects from alcohol, and 100 represents "extremely" experiencing alcohol effects.
| score on a scale | Placebo Medication Dose | Perampanel 6mg Dose | Perampanel 10mg Dose |
|---|---|---|---|
| Drug Effects Questionaire (DEQ) | 42.538 ± 3.379 | 40.619 ± 3.269 | 43.267 ± 3.442 |
A valid eight-item Likert-type scale designed to assess acute alcohol craving. Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. A total score is computed by averaging the item scores. Higher scores reflect greater craving. The minimum score is 7, and the maximum is 49. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
| score on a scale | Placebo Medication Dose | Perampanel 6mg Dose | Perampanel 10mg Dose |
|---|---|---|---|
| Alcohol Urge Questionnaire (AUQ) | 16.481 ± 1.266 | 17.314 ± 1.177 | 18.723 ± 1.289 |
This consists of a list of side effects associated with perampanel (e.g., fatigue, dizziness), rated from 0="none" to 4="severe". The mean for each subject across all items is included in each group/arm mean. The lowest score on the scale would be 0 and the maximum 4, as the mean across items is taken and not a sum. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).
| score on a scale | Placebo Medication Dose | Perampanel 6mg Dose | Perampanel 10mg Dose |
|---|---|---|---|
| Side Effect Questionnaire (SEQ) | 0.895 ± .294 | .992 ± .261 | 1.13 ± .280 |
The Profile of Mood States (POMS) 2 short version contains a subset of 35 items from the full-length versions. This subset comprises those five items on full version POMS scale that exhibited good item-total correlations and best predicted their respective scale scores, this is a TOTAL score Representing total mood disturbance. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes). The minimum is 0 and the maximum is 100 with higher numbers indicating greater mood disturbance.
| score on a scale | Placebo Medication Dose | Perampanel 6mg Dose | Perampanel 10mg Dose |
|---|---|---|---|
| Profile of Mood States (POMS) 2 Short Version Total Score | 20.25 ± 1.490 | 21.75 ± 1.335 | 20.619 ± 1.533 |
Collected over 40 days of participation. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/22 (0%) | 0/22 (0%) | 4/22 (18.2%) |
| Perampanel 6mg | 0/22 (0%) | 0/22 (0%) | 1/22 (4.5%) |
| Perampanel 10 mg | 0/22 (0%) | 0/22 (0%) | 4/22 (18.2%) |
| Event | Placebo | Perampanel 6mg | Perampanel 10 mg |
|---|---|---|---|
| nausea/vomitingGastrointestinal disorders | 1/22 | 0/22 | 2/22 |
| IV site bruising/thrombosisSkin and subcutaneous tissue disorders | 1/22 | 1/22 | 0/22 |
| Viral cold symptomsInfections and infestations | 1/22 | 0/22 | 0/22 |
| dysuriaRenal and urinary disorders | 1/22 | 0/22 | 0/22 |
| Dry MouthGastrointestinal disorders | 0/22 | 0/22 | 1/22 |
| FatiguePsychiatric disorders | 0/22 | 0/22 | 1/22 |
Non-treatment seeking heavy drinkers- This is a crossover design. Subjects each completed at least one of the three dosages for a lab day.
| Age, Categorical(Participants) | Combined Group Crossover Study - Placebo/6mg/10mg |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 22 |
| >=65 years | 0 |
| Age, Continuous(years) | Combined Group Crossover Study - Placebo/6mg/10mg |
|---|---|
| Mean | 28.1 ± 8.1 |
| Sex: Female, Male(Participants) | Combined Group Crossover Study - Placebo/6mg/10mg |
|---|---|
| Female | 14 |
| Male | 8 |
| Race (NIH/OMB)(Participants) | Combined Group Crossover Study - Placebo/6mg/10mg |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 3 |
| White | 15 |
| More than one race | 2 |
| Unknown or Not Reported | 1 |
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Virginia Commonwealth University