Rapid Determination Of The Clinical Utility Of Perampanel For The Treatment Of Alcohol Dependence

Virginia Commonwealth University (VCU)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Alcoholism

Treatments: Drug: Placebo; Drug: Perampanel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02120365

1407014397 (Other Identifier)

R21AA026681 (U.S. NIH Grant/Contract)

HM20014446

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 22 patients

Sex: All

Ages: 21 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• males and females
• between the ages of 21 and 55 years;
• Nontreatment-seeking Heavy Drinkers (NTSHDs)as defined above, and must have had at least 5 Standard Drinks (SD) in one day on at least some occasions in the past and been able to tolerate it without an adverse reaction
• generally medically and neurologically healthy on the basis of history, physical examination, Electrocardiogram, screening laboratory results (Complete Blood Count w/ differential, Thyroid Stimulating Hormone, Free-T4, Aspartate Transferase, Alanine Transferase, Gamma-Glutamyl Transferase, Blood Urea Nitrogen, creatinine, electrolytes, urinalysis, beta-Human Chorionic Gonadotropin). Individuals with Liver Function Tests (LFT) that are no more than 3 times above the normal levels will be included;
• women with a negative pregnancy test and not nursing, must be regularly using birth control
• negative breath alcohol at screening and on each test day;
• not taking any psychoactive medication or opioids (in past 30-days);
• are non-treatment seeking.

Exclusion criteria

• they need detoxification determined by a Clinical Institute Withdrawal Assessment (CIWA) score of >8 or have had a history of alcohol detoxification in the past;
• have been in treatment for an alcohol problem within the last 6 months, or if the severity of their alcohol problem based on the research physician's assessment warrants definitive treatment;
• meet criteria for Diagnostic Statistical Manual (DSM) -IV psychiatric and substance use disorder diagnosis (other than alcohol abuse/dependence, cannabis abuse/dependence and nicotine dependence; those diagnoses will be allowed; participants can be either smokers up to 1 pack per day or non-smokers) based on history and psychiatric evaluation that includes a structured diagnostic interview (Structured Clinical Interview for DSM-IV Axis I Disorders: SCID)
• unwillingness to remain alcohol-free 12 hours prior to test days;
• have a significant ongoing serious medical condition such as Diabetes Mellitus, liver disease (see above LFT guideline), renal disease (as evidenced by serum creatinine above our laboratory's reference limit of 1.7 mg/dL, or have a history of adverse reaction to IV placement/blood draw

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

22 participants in 3 patient groups, including a placebo group

Perampanel 6mg

Experimental group

Description:

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.

Treatment:

Drug: Perampanel

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Perampanel 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Perampanel