A Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lorenzo Leggio, Brown University
ClinicalTrials.gov Identifier:
NCT01076283
First received: February 25, 2010
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

This pilot trial has the goal to demonstrate the feasibility of a study to test the effects of baclofen in a laboratory experiment using cue-reactivity and alcohol-self administration paradigms in non-treatment seeking alcohol-dependent subjects.


Condition Intervention Phase
Alcoholism
Drug: Baclofen
Drug: Cyproheptadine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Pilot Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Alcohol Urge [ Time Frame: approximately 8 days after drug administration ] [ Designated as safety issue: No ]

    Whether baclofen, as compared to active placebo, results in diminished cue-reactivity responses to alcohol cues in terms of urge to drink [as measured by the Alcohol Urge Questionnaire (AUQ)] during the Cue Reactivity.

    The Alcohol Urge Questionnaire (AUQ) consists of eight statements about the respondent's feelings and thoughts about drinking as they are completing the questionnaire (i.e., right now). The respondent is asked to respond to each statement about alcohol craving via a 7-item Likert scale ranging from "strongly disagree" to "strongly agree." 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 summing the item scores and ranges from 8 (lowest craving value) to 56 (highest craving value). Higher scores reflect greater craving (i.e. worse outcome).


  • Alcohol Drinking [ Time Frame: approximately 8 days after drug administration ] [ Designated as safety issue: Yes ]

    Whether baclofen, as compared to active placebo, results in lower quantity of alcohol consumed during the Alcohol Self-Administration (ASA).

    Consistent with O'Malley et al. 2002, the ASA paradigm allows to use a fixed-dose (the priming drink), followed by a 2-hour "free-choice" phase when subjects may choose to drink or not up to 8 mini-drinks. Participants receive a monetary compensation of $3 dollars per each mini-drink not consumed; therefore the amount of minidrinks consumed during the 2-hour sessions ranges 0-8, and the monetary compensation ranges $0-24. The quantity of alcohol consumed during the free-choice session is expressed as "standard drinking unit", where a standard drink unit contains about 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons).



Enrollment: 14
Study Start Date: December 2009
Study Completion Date: May 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Baclofen
Baclofen 10 mg three times a day (t.i.d.) for 8-10 days
Drug: Baclofen
Baclofen 10mg t.i.d.
Placebo Comparator: Cyproheptadine
Cyproheptadine 2 mg t.i.d. for 8-10 days
Drug: Cyproheptadine
'active' placebo

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • must be male or female between 21 and 65 years old (inclusive).
  • participants must meet criteria for current Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) diagnosis of alcohol dependence, supported by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Patient Edition (SCID-I/P).
  • participants must meet criteria for heavy drinking, defined as averaging ≥4 drinks/day for women and ≥5 drinks/day for men during a consecutive 30-day period within the 90 days prior to baseline evaluation (see: Anton et al, 2006). The gender-specific baseline was chosen as it represents heavy drinking that exceeds empirically based levels of moderate alcohol use that result in alcohol-related problems for women who consume ≥4 drinks/day, and men who consume ≥5 drinks/day (Sanchez-Craig et al, 1995).
  • participants must be in good health as confirmed by medical history, physical examination, ECG, lab tests.
  • females must be postmenopausal for at least one year, surgically sterile, or practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at each visit.
  • participants must be willing to take oral medication and adhere to the study procedures.

Exclusion criteria:

  • individuals expressing interest in treatment for alcoholism.
  • pregnancy or breast feeding women or not using an adequate form of birth control
  • positive urine drug screen at baseline for any illegal substance (a urine drug screen may be repeated once during the screening period).
  • individuals diagnosed with a current substance dependence diagnosis, other than alcohol or nicotine.
  • meet DSM-IV Axis I criteria for a lifetime diagnosis of schizophrenia, bipolar disorder, or other psychoses.
  • an active illness within the past 6 months of Visit 1 that meet the DSM-IV criteria for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder. Subjects with a history of suicide will be excluded.
  • clinically significant medical abnormalities (i.e., unstable hypertension, ECG, bilirubin > 150% of the upper normal limit, ALT or AST elevations >300% the upper normal limit, creatinine clearance ≤ 60 dl/min).
  • current use of psychotropic medications that cannot be discontinued that may have an effect on alcohol consumption or that may interact with baclofen or cyproheptadine.
  • medical contraindications for use of baclofen or cyproheptadine.
  • a history of adverse reaction or hypersensitivity to baclofen or cyproheptadine.
  • individuals with a reasonable expectation of being institutionalized during the course of the trial.
  • participants who have significant alcohol withdrawal symptoms, defined as a Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) >10.
  • history of seizures (e.g. epilepsy).
  • subjects who have participated in any behavioral and/or pharmacological study within the past 90 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01076283

Locations
United States, Rhode Island
Brown University Center for Alcohol and Addiction Studies
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
Brown University
Investigators
Principal Investigator: Lorenzo Leggio, M.D., M.Sc. Brown University Center for Alcohol and Addiction Studies
  More Information

Publications:

Responsible Party: Lorenzo Leggio, Assistant Professor (Research), Brown University
ClinicalTrials.gov Identifier: NCT01076283     History of Changes
Other Study ID Numbers: 0906000002
Study First Received: February 25, 2010
Results First Received: May 5, 2013
Last Updated: October 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Brown University:
baclofen
alcoholism
urge
craving
alcohol drinking
biobehavioral mechanisms of baclofen in alcoholism

Additional relevant MeSH terms:
Alcoholism
Alcohol Drinking
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Drinking Behavior
Cyproheptadine
Antipruritics
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Serotonin Antagonists
Serotonin Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on September 29, 2014