Treating Alcohol Withdrawal With Oral Baclofen

• ClinicalTrials.gov Identifier: NCT00597701
• Recruitment Status: Completed
• First Posted: January 18, 2008
• Results First Posted: July 26, 2011
• Last Update Posted: July 27, 2011
• Sponsor: Essentia Health
• Information provided by: Essentia Health

Study Description

Brief Summary:

The purpose of this study is determine if subjects with alcohol withdrawal who receive oral baclofen, plus standard benzodiazepine therapy, will experience less severe withdrawal symptoms than those who receive placebo plus standard benzodiazepine therapy.Subjects with alcohol withdrawal syndrome(AWS)who receive baclofen plus standard benzodiazepine therapy will experience fewer complications of AWS (as measured by use of additional sedatives, restraints, and/or intensive care unit [ICU] admissions) compared with subjects who receive placebo plus standard benzodiazepine therapy.

Condition or disease	Intervention/treatment	Phase
Alcohol Withdrawal Delirium	Drug: Baclofen; Drug: Placebo; Drug: Lorazepam	Not Applicable

Detailed Description:

Alcohol use is ubiquitous in American society. 83% of Americans have ever consumed alcohol, 51% have in the lst month.

The average American consumes 2.18 gallons of ethanol yearly. Alcohol related morbidity and mortality are staggering problems in the USA. Symptoms of alcohol withdrawal occur because alcohol is a central nervous system depressant; abrupt withdrawal unmasks compensatory overactivity of certain parts of the nervous system, including sympathetic autonomic outflow. 5% of patients who undergo alcohol suffer from Delirium Tremors (DTs), a syndrome characterized by hallucinations, disorientation, tachycardia, hypertension, low grade fever, agitation, and diaphoresis.

DTs typically begin between 48-96 hours after the last drink and last 1 to 5 days. DTs requires hospitalization and vigorous activity in an ICU setting.

The most successful drug treatment for alcohol withdrawal has been found to be the benzodiazepines.

Symptom triggered treatment was found to be as effective as a fixed dose treatment to result in less drug being used overall, with a trend toward shorter duration of withdrawal treatment.

Baclofen is used orally for the treatment of spasticity resulting from multiple sclerosis, spinal cord injuries/diseases and intrathecally for spasticity related to cerebral palsy, spinal cord injury, and amyotrophic lateral sclerosis (ALS).

Its proposed benefit in alcohol withdrawal is that it may reduce voluntary alcohol intake, alcohol craving, and may suppress the intensity of alcohol withdrawal treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Treating Alcohol Withdrawal With Oral Baclofen: a Randomized, Double Blind, Placebo Controlled Trial
• Study Start Date: April 2003
• Actual Primary Completion Date: February 2008
• Actual Study Completion Date: February 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Baclofen; Standard benzodiazepine therapy plus baclofen 10 mg every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours.	Drug: Baclofen; Baclofen 10 mg by mouth every 8 hours for 72 hours or until discharge if before 72 hours.; Other Name: Lioresal; Drug: Lorazepam; Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard "symptom-triggered dosing" of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.
Placebo Comparator: Placebo; Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.	Drug: Placebo; Placebo; Drug: Lorazepam; Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard "symptom-triggered dosing" of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.

Outcome Measures

Primary Outcome Measures :

1. Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups [ Time Frame: From eligibility for randomization (Clinical Institute Withdrawal Assessment [CIWA] score of at least 11) until 72 hours of observation had been completed. ]
   In acutely-withdrawing alcoholic patients treated with either baclofen or placebo, symptom-driven benzodiazepine doses were assessed for the 72 hours following the first Clinical Institute Withdrawal Assessment (CIWA) score of 11 or greater.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meet Diagnostic and Statistical Manual, 4th version, revised (DSMr-IV) criteria for alcohol withdrawal syndrome (AWS).
• Be an inpatient at St. Mary's Medical Center (SMMC) or Miller Dwan Medical Center (MDMC) at time of study enrollment.
• Have an alcohol withdrawal score as measured by standard SMMC or MDMC inpatient protocol sufficient to trigger the use of benzodiazepine withdrawal therapy.
• Agree to abstain for alcohol for duration of study.
• Be able to provide informed consent.

Exclusion Criteria:

• The patient must not have any other active drug dependence in addition to alcohol.
• Be unwilling or unable to forgo alcohol for the duration of the study.
• Be using baclofen at the time of study enrollment.
• Be using benzodiazepines for any reason other than acute alcohol withdrawal syndrome at time of study enrollment.
• have known baclofen or benzodiazepine sensitivity.
• Be unable to take oral (PO) meds.
• Be unable to complete one of two consenting procedures.
• Be pregnant or breastfeeding.
• Have a serum creatine level > 2.0.
• Have a history of non alcoholic withdrawal seizures.

Contacts and Locations

Locations

United States, Minnesota

Essentia Health

Duluth, Minnesota, United States, 55805

Sponsors and Collaborators

Essentia Health

Investigators

• Principal Investigator: Jeffrey Lyon, MD; Essentia Health

More Information

Publications:

Colombo G, Agabio R, Carai MA, Lobina C, Pani M, Reali R, Addolorato G, Gessa GL. Ability of baclofen in reducing alcohol intake and withdrawal severity: I--Preclinical evidence. Alcohol Clin Exp Res. 2000 Jan;24(1):58-66.

Addolorato G, Caputo F, Capristo E, Janiri L, Bernardi M, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Rapid suppression of alcohol withdrawal syndrome by baclofen. Am J Med. 2002 Feb 15;112(3):226-9. doi: 10.1016/s0002-9343(01)01088-9. No abstract available.

• Responsible Party: Jeffrey Lyon, MD, Essentia Health
• ClinicalTrials.gov Identifier: NCT00597701
• Other Study ID Numbers: 090403
• First Posted: January 18, 2008
• Results First Posted: July 26, 2011
• Last Update Posted: July 27, 2011
• Last Verified: July 2011

Keywords provided by Essentia Health:

Alcohol withdrawal; Delirium tremors

Additional relevant MeSH terms:

Delirium; Alcohol Withdrawal Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Alcohol-Induced Disorders, Nervous System; Neurotoxicity Syndromes; Poisoning; Chemically-Induced Disorders; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Lorazepam; Baclofen; Muscle Relaxants, Central; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents; GABA-B Receptor Agonists; GABA Agonists; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anticonvulsants; Antiemetics; Autonomic Agents