Alcohol Disorders
Conditions
Brief summary
The purpose of this research study is to test the safety, tolerability, and effectiveness of the drug Perampanel when used in persons who drink and wish to stop drinking. Perampanel has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures but has not yet been approved to treat alcohol use disorders. For this reason, it is considered an investigational drug. Some people in this study will receive Perampanel alone and some people will receive Perampanel and Disulfiram, this will be determined by the pharmacy.
Detailed description
Participants will be asked to take a medication (Perampanel or Perampanel + Disulfiram) every day for approximately 8 weeks and have weekly study visits. At these visits, participants will be asked questions about their medical history, drinking behavior and life events, have bloodwork checked routinely, have regular medication counseling, and perform some computer tasks. Throughout the study, there will be regular phone calls from staff. Participants will also be asked to use a device called Soberlink which is like an at-home breathalyzer test to help track progress throughout the study. Participants will be randomly assigned (like the flip of a coin) to receive either Perampanel alone or Peramanel and Disulfiram. Participation in this study will last up to 10 weeks. Approximately 20 individuals will participate in this study. This study will sequence all or part of participant's DNA. This is a necessary part of the study. Before starting the study, participants may be referred to an alcohol detoxification program (medical treatment of an alcoholic), if clinically indicated.
Interventions
Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups
DRUGDisulfiram
Disulfiram will be kept at 250mg daily
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
20 subjects with AUD will be randomized 1:1 to one of two groups; perampanel by itself, and perampanel combined with disulfiram.
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women ages 21-70 with DSM-5 AUD; 2. regular heavy drinkers as defined by averaging ≥ 2 heavy drinking days per week over the 60 days baseline pre-treatment TLFB, and recognize a need to completely stop drinking; 3. willingness to provide written, informed consent to participate in the study; 4. Individuals with LFTs that are no more than 2-3 times above the normal levels and with a Child-Pugh score of no greater than 5 will be included and 5. women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation or \<2 years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative serum pregnancy test prior to initiation of treatment.
Exclusion criteria
1. a current, clinically significant physical disease \[i.e., neurologic, renal, pulmonary, cardiovascular, hepatic\] on the basis of medical history, physical examination, or routine laboratory evaluation that, in the context of the study would represent a risk to the subject, or significant laboratory abnormalities related to hepatic function such as marked elevations of hepatic aminotransferase levels (i.e., AST and ALT) or direct bilirubin; 2. history of renal compromise or current renal disease (as evidenced by serum creatinine above our laboratory's reference limit of 1.7 mg/dL; 3. history of seizure disorder; 4. use of any of a number of medications that might prominently influence drinking patterns or cause risk of harm or injury (e.g., other anticonvulsants, medications to treat AUD, opioid pain medication), currently taking CNS depressants (e.g. benzodiazepines, barbiturates, sedating antihistamines; 5. schizophrenia, bipolar disorder, current major depressive episode, or substantial suicide or violence risk on the basis of history or psychiatric examination; 6. currently dependent on stimulants, opioids or sedatives; 7. subjects with any substantial alcohol withdrawal will be required to be detoxified by regular clinical services prior to study entry; 8. are currently taking any medication that is a moderate to strong CYP3A4 inhibitor or inducer if participants are required to initiate these medications by an outside provider during the course of this study, they will be tapered off the study regimen and we will have them terminate early) 9. are taking phenytoin or warfarin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Abstinent Days | End of treatment, up to 12 weeks | Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Alcohol Craving | Baseline to end of treatment, up to 12 weeks | Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving. |
| Percent Heavy Drinking Days | End of treatment, Up to 8 weeks | Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perampanel by Itself Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups | 2 |
| Perapanel With Disulfiram Perampanel Tablet: Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups
Disulfiram: Disulfiram will be kept at 250mg daily | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Perampanel by Itself | Perapanel With Disulfiram | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 | 0 / 2 |
Outcome results
Primary
Percent Abstinent Days
Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period.
Time frame: End of treatment, up to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Perampanel by Itself | Percent Abstinent Days | 3.13 Percentage of days |
| Perapanel With Disulfiram | Percent Abstinent Days | 100 Percentage of days |
Secondary
Change in Alcohol Craving
Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving.
Time frame: Baseline to end of treatment, up to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Perampanel by Itself | Change in Alcohol Craving | 4 score on a scale |
| Perapanel With Disulfiram | Change in Alcohol Craving | -1 score on a scale |
Secondary
Percent Heavy Drinking Days
Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period.
Time frame: End of treatment, Up to 8 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Perampanel by Itself | Percent Heavy Drinking Days | 73.60 percentage of days |
| Perapanel With Disulfiram | Percent Heavy Drinking Days | 0 percentage of days |