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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02120365
Recruitment Status : Recruiting
First Posted : April 22, 2014
Last Update Posted : October 19, 2020
Sponsor:
Collaborators:
University of Connecticut
Yale University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Virginia Commonwealth University

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.

Condition or disease Intervention/treatment Phase
Alcoholism Drug: Perampanel Drug: Placebo Phase 1 Phase 2

Detailed Description:
The main goal of the proposed study is to determine whether the 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), 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Rapid Determination Of The Clinical Utility Of Perampanel For The Treatment Of Alcohol Dependence
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Perampanel

Arm Intervention/treatment
Experimental: Parampanel 6mg
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 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.
Other Names:
  • AMPA-R antagonist
  • anticonvulsant

Placebo Comparator: Placebo
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 BrAc=20mg%, 60mg%, and 100mg%) in a step-wise fashion.
Drug: Placebo
Placebo given in place of perampanel during the pre-treatment period and lab session days.

Experimental: Parampanel 10 mg
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 parempanel (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 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.
Other Names:
  • AMPA-R antagonist
  • anticonvulsant




Primary Outcome Measures :
  1. Biphasic Alcohol Effects Scale (BAES) [ Time Frame: Day 8 ]
    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.

  2. Biphasic Alcohol Effects Scale (BAES) [ Time Frame: Day 24 ]
    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.

  3. Biphasic Alcohol Effects Scale (BAES) [ Time Frame: Day 40 ]
    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.

  4. Drug Effects Questionaire (DEQ) [ Time Frame: Day 8 ]
    consists of four items that measure current alcohol effects: 'feel alcohol', 'feel high', 'like alcohol', and 'want more alcohol'.

  5. Drug Effects Questionaire (DEQ) [ Time Frame: Day 24 ]
    consists of four items that measure current alcohol effects: 'feel alcohol', 'feel high', 'like alcohol', and 'want more alcohol'.

  6. Drug Effects Questionaire (DEQ) [ Time Frame: Day 40 ]
    consists of four items that measure current alcohol effects: 'feel alcohol', 'feel high', 'like alcohol', and 'want more alcohol'.


Secondary Outcome Measures :
  1. Visual Analog Scales of Mood States (VAS) [ Time Frame: Day 8, 24, and 0 ]
    A 5-item scale designed to assess subjective alcohol effects: high, anxious, drowsy, irritable, and nauseous. It has been used in previous studies by our group and has good sensitivity to drug effect.

  2. Alcohol Urge Questionnaire (AUQ) [ Time Frame: Day 8, 24, and 40 ]
    A valid eight-item Likert-type scale designed to assess acute alcohol craving

  3. Subjective High Assessment Scale (SHAS) [ Time Frame: Day 8, 24, 40 ]
    We will use the SHAS7, a reliable and valid 7-item scale assessing the amount (ranging from 0-36) of each experiential item (e.g., feeling "drunk" or "high") related to alcohol exposure

  4. Side Effect Questionnaire (SEQ) [ Time Frame: Day 8, 24, 40 ]
    This consists of a list of side effects associated with perampanel (e.g., fatigue, dizziness), rated from 0="none" to 4="severe".

  5. Profile of Mood States (POMS) 2 Short Versions [ Time Frame: Day 8, 24, 40 ]
    The 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

  6. Stop Signal Test (SST, also know as Go/No-Go) [ Time Frame: Day 8, 24, 40 ]
    SST is a commonly used test of response inhibition. This test consists of two parts. In the first part, the subject is introduced to the press pad, and told to press the left hand button when they see a left-pointing arrow or press the right hand button when they see a right-pointing arrow. There is one block of 16 trials for the subject to practice this. In the second part, the subject is told to continue pressing the buttons on the press pad when they see the arrows, as before, but, if they hear an auditory signal (a beep), they should withhold their response and not press the button.

  7. The Balloon Analogue Risk Task (BART) [ Time Frame: Day 8, 24, and 40 ]
    This is a valid and commonly used test of risk-taking, an aspect of impulsivity. This task is computerized, and subjects press a button to analogously pump air into a balloon on the screen. Subjects are told they can earn 1 cent for each pump of the balloon banked to a reward account before they cash out and stop pumping. The balloons break at various random intervals and if the balloon breaks, the subjects lose money out of the reward account. We will use a 10-balloon paradigm, a briefer but valid version of this task. They can earn a maximum of 7.5 dollars per administration, with 4 administrations per lab, for a total of up to $90 additional pay over the course of the study, though actual payouts will likely be substantially less.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • males and females
  • between the ages of 21 and 55 years;
  • NTSHDs as defined above, and must have had at least 5 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, EKG, screening laboratory results (CBC w/ differential, TSH, Free-T4, AST, ALT, GGT, BUN, creatinine, electrolytes, urinalysis, beta-HCG). Individuals with LFTs 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 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 DSM-IV psychiatric and substance use disorder diagnosis (other than alcohol 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02120365


Contacts
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Contact: Albert Arias, MD 804-828-5793 albert.arias@vcuhealth.org
Contact: MaryAnne Harmon 804-828-1697 Harmonm@vcu.edu

Locations
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United States, Connecticut
University of Connecticut Recruiting
Farmington, Connecticut, United States, 06030
Contact: Marcia Lawlor, B.A.    860-679-8979    lawlor@uchc.edu   
Yale New Haven Hospital Research Unit Completed
New Haven, Connecticut, United States, 06510
West Haven Veterans Affairs Completed
West Haven, Connecticut, United States, 06515
United States, Virginia
Albert Arias Recruiting
Richmond, Virginia, United States, 23219
Contact: Albert Arias, MD    804-828-5793    albert.arias@vcuhealth.org   
Contact: MaryAnne Harmon, NP    804-828-1697    harmonm@vcu.edu   
Sponsors and Collaborators
Virginia Commonwealth University
University of Connecticut
Yale University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
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Principal Investigator: Albert Arias, MD Virginia CommonwealthUniversity
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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02120365    
Other Study ID Numbers: HM20014446
1407014397 ( Other Identifier: Yale University )
R21AA026681 ( U.S. NIH Grant/Contract )
First Posted: April 22, 2014    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Virginia Commonwealth University:
Alcoholism
Heavy Drinking
Perampanel
Additional relevant MeSH terms:
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Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Anticonvulsants