A Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking

NCT ID: NCT01076283

Last Updated: 2013-10-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-31

Study Completion Date

2010-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Alcoholism

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Baclofen

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

Group Type ACTIVE_COMPARATOR

Baclofen

Intervention Type DRUG

Baclofen 10mg t.i.d.

Cyproheptadine

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

Group Type PLACEBO_COMPARATOR

Cyproheptadine

Intervention Type DRUG

'active' placebo

Interventions

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Baclofen

Baclofen 10mg t.i.d.

Intervention Type DRUG

Cyproheptadine

'active' placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Brown University

OTHER

Sponsor Role lead

Responsible Party

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Lorenzo Leggio

Assistant Professor (Research)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lorenzo Leggio, M.D., M.Sc.

Role: PRINCIPAL_INVESTIGATOR

Brown University Center for Alcohol and Addiction Studies

Locations

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Brown University Center for Alcohol and Addiction Studies

Providence, Rhode Island, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 20201813 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18840257 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18068515 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16490478 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14520166 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15719231 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15545024 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12217947 (View on PubMed)

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.

Reference Type RESULT
PMID: 23262301 (View on PubMed)

Other Identifiers

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0906000002

Identifier Type: -

Identifier Source: org_study_id