Alcoholism
Conditions
Keywords
baclofen, alcoholism, urge, craving, alcohol drinking, biobehavioral mechanisms of baclofen in alcoholism
Brief summary
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.
Interventions
DRUGBaclofen
Baclofen 10mg t.i.d.
DRUGCyproheptadine
'active' placebo
Sponsors
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Urge | approximately 8 days after drug administration | 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 | approximately 8 days after drug administration | 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). |
Countries
United States
Participant flow
Recruitment details
Potential participants came for an in-person screening (Visit 1) at the Brown University Center for Alcohol and Addiction Studies (CAAS). At Visit 2 (day 1), participants were randomized to either baclofen or active placebo by using a 3-urn variable procedure (Stout et al., 1994), i.e. gender, FH of alcoholism and baseline drinks per drinking day.
Pre-assignment details
19 participants signed the consent document; 5 of them did not satisfy the protocol-specific inclusion/exclusion criteria, therefore they were excluded from the trial. The remaining 14 subjects were assigned to the study groups.
Participants by arm
| Arm | Count |
|---|---|
| Baclofen Baclofen 10 mg three times a day (t.i.d.) for 8-10 days | 7 |
| Cyproheptadine Cyproheptadine 2 mg t.i.d. for 8-10 days | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Baclofen | Cyproheptadine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 7 participants | 7 participants | 14 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 7 | 3 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Alcohol Drinking
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).
Time frame: approximately 8 days after drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen | Alcohol Drinking | 0.17 standard drinking units | Standard Deviation 0.41 |
| Cyproheptadine | Alcohol Drinking | 1.43 standard drinking units | Standard Deviation 2.3 |
Primary
Alcohol Urge
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).
Time frame: approximately 8 days after drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen | Alcohol Urge | 22.5 units on a scale | Standard Deviation 11.4 |
| Cyproheptadine | Alcohol Urge | 19.4 units on a scale | Standard Deviation 19.6 |