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

Alcoholism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02120365
• Other study ID #: HM20014446
• Secondary ID: 1407014397R21AA0
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 1, 2019
• Est. completion date: February 16, 2022

Study information

• Verified date: August 2023
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 16, 2022
• Est. primary completion date: February 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcoholism

Intervention

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.
• Placebo
Placebo given in place of perampanel during the pre-treatment period and lab session days.

Locations

Country	Name	City	State
United States	University of Connecticut	Farmington	Connecticut
United States	Yale New Haven Hospital Research Unit	New Haven	Connecticut
United States	Albert Arias	Richmond	Virginia
United States	West Haven Veterans Affairs	West Haven	Connecticut

Sponsors (4)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Institute on Alcohol Abuse and Alcoholism (NIAAA), University of Connecticut, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	98 minutes
Primary	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).	98 minutes
Primary	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.	98 min
Secondary	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).	98 min
Secondary	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).	98 minutes
Secondary	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.	98 minutes