Treating Alcohol Withdrawal With Oral Baclofen

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Treating Alcohol Withdrawal With Oral Baclofen: a Randomized, Double Blind, Placebo Controlled Trial

Conditions
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Alcohol Withdrawal Delirium

Intervention / Treatment
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* Drug: Baclofen
* Drug: Placebo
* Drug: Lorazepam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Baclofen<br>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<br>* Baclofen 10 mg by mouth every 8 hours for 72 hours or until discharge if before 72 hours.<br>* Other names: Lioresal;Drug: Lorazepam<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours. | Drug: Placebo<br>* Placebo<br>Drug: Lorazepam<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups | 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. | From eligibility for randomization (Clinical Institute Withdrawal Assessment [CIWA] score of at least 11) until 72 hours of observation had been completed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol withdrawal, Delirium tremors