Clinical trial NCT02120365: Rapid Determination Of The Clinical Utility Of Perampanel For The Treatment Of Alcohol Dependence
Official title: Rapid Determination Of The Clinical Utility Of Perampanel For The Treatment Of Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alcoholism
Keywords: Alcoholism
Heavy Drinking
Perampanel
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: University of Connecticut
name: Yale University
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2014-04-22
Enrollment: 22
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Biphasic Alcohol Effects Scale (BAES): Stimulant Subscale
timeFrame: 98 minutes
measure: Biphasic Alcohol Effects Scale (BAES)- Sedative Subscale
timeFrame: 98 minutes
measure: Drug Effects Questionaire (DEQ)
timeFrame: 98 min
Secondary outcomes:
measure: Alcohol Urge Questionnaire (AUQ)
timeFrame: 98 min
measure: Side Effect Questionnaire (SEQ)
timeFrame: 98 minutes
measure: Profile of Mood States (POMS) 2 Short Version Total Score
timeFrame: 98 minutes
Other outcomes:
Locations:
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital Research Unit
state: Connecticut
city: West Haven
country: United States
facility: West Haven Veterans Affairs
state: Connecticut
city: Richmond
country: United States
facility: Albert Arias
state: Virginia
Study officials:
affiliation: Virginia CommonwealthUniversity
name: Albert Arias, MD
role: PRINCIPAL_INVESTIGATOR
References: