A Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking

NCT01076283 | Completed Phase 2 Results

• 1 other identifier: 0906000002
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcoholism

Keywords

baclofen; alcoholism; urge; craving; alcohol drinking; biobehavioral mechanisms of baclofen in alcoholism

Outcome Measures

Primary Outcomes (2)

• 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).

  approximately 8 days after drug administration

• 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).

  approximately 8 days after drug administration

Study Arms (2)

Baclofen

ACTIVE COMPARATOR

Baclofen 10 mg three times a day (t.i.d.) for 8-10 days

Drug: Baclofen

Cyproheptadine

PLACEBO COMPARATOR

Cyproheptadine 2 mg t.i.d. for 8-10 days

Drug: Cyproheptadine

Interventions

Baclofen DRUG

Baclofen 10mg t.i.d.

Baclofen

Cyproheptadine DRUG

'active' placebo

Cyproheptadine

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brown University: lead

Study Sites (1)

Brown University Center for Alcohol and Addiction Studies

Providence, Rhode Island, 02903, United States

Location

Related Publications (9)

• Leggio L, Garbutt JC, Addolorato G. Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol Disord Drug Targets. 2010 Mar;9(1):33-44. doi: 10.2174/187152710790966614.

  PMID: 20201813 BACKGROUND

• Evans SM, Bisaga A. Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcohol Clin Exp Res. 2009 Jan;33(1):19-30. doi: 10.1111/j.1530-0277.2008.00805.x. Epub 2008 Oct 6.

  PMID: 18840257 BACKGROUND

• Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, D'Angelo C, Caputo F, Zambon A, Haber PS, Gasbarrini G. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007 Dec 8;370(9603):1915-22. doi: 10.1016/S0140-6736(07)61814-5.

  PMID: 18068515 BACKGROUND

• Addolorato G, Leggio L, Abenavoli L, Agabio R, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G. Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam. Am J Med. 2006 Mar;119(3):276.e13-8. doi: 10.1016/j.amjmed.2005.08.042.

  PMID: 16490478 BACKGROUND

• Addolorato G, Leggio L, Abenavoli L, DeLorenzi G, Parente A, Caputo F, Janiri L, Capristo E, Rapaccini GL, Gasbarrini G. Suppression of alcohol delirium tremens by baclofen administration: a case report. Clin Neuropharmacol. 2003 Sep-Oct;26(5):258-62. doi: 10.1097/00002826-200309000-00010.

  PMID: 14520166 BACKGROUND

• Addolorato G, Leggio L, Abenavoli L, Caputo F, Gasbarrini G. Tolerance to baclofen's sedative effect in alcohol-addicted patients: no dissipation after a period of abstinence. Psychopharmacology (Berl). 2005 Mar;178(2-3):351-2. doi: 10.1007/s00213-004-2014-4. Epub 2004 Sep 30. No abstract available.

  PMID: 15719231 BACKGROUND

• Colombo G, Addolorato G, Agabio R, Carai MA, Pibiri F, Serra S, Vacca G, Gessa GL. Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics. Neurotox Res. 2004;6(5):403-14. doi: 10.1007/BF03033315.

  PMID: 15545024 BACKGROUND

• Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M, Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8. doi: 10.1093/alcalc/37.5.504.

  PMID: 12217947 BACKGROUND

• Leggio L, Zywiak WH, McGeary JE, Edwards S, Fricchione SR, Shoaff JR, Addolorato G, Swift RM, Kenna GA. A human laboratory pilot study with baclofen in alcoholic individuals. Pharmacol Biochem Behav. 2013 Feb;103(4):784-91. doi: 10.1016/j.pbb.2012.11.013. Epub 2012 Dec 19.

  PMID: 23262301 RESULT

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking

Interventions

Baclofen; Cyproheptadine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

Very small sample. This pilot trial was primarily aimed to determine a power analysis for future larger trials.

Results Point of Contact

• Title: Lorenzo Leggio, MD
• Organization: Brown University

lorenzoleggio@gmail.com

401-863-1000

Study Officials

• Lorenzo Leggio, M.D., M.Sc.

  Brown University Center for Alcohol and Addiction Studies

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor (Research)

Study Record Dates

• First Submitted: February 25, 2010
• First Posted: February 26, 2010
• Study Start: December 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: October 17, 2013
• Results First Posted: October 17, 2013

Record last verified: 2013-10

Locations

US (1)