Treating Alcohol Withdrawal With Oral Baclofen

• Sponsor: Essentia Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00597701
• Collaborator: (none)
• Enrollment: 79
• Location: 1
• Arms: 2
• Duration (Months): 58.1
• Patients Per Site Per Month: 1.4

Study Details

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	N/A

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
• 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: Apr 1, 2003
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 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 Names: 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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Essentia Health	Duluth	Minnesota	United States	55805

Sponsors and Collaborators

• Essentia Health

Investigators

• Principal Investigator: Jeffrey Lyon, MD, Essentia Health

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• ClinicalTrials.gov Identifier: NCT00597701
• Other Study ID Numbers: 090403
• First Posted: Jan 18, 2008
• Last Update Posted: Jul 27, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: Alcohol withdrawal; Delirium tremors
• Additional relevant MeSH terms: Delirium; Alcohol Withdrawal Delirium; Lorazepam; Baclofen

Study Results

Participant Flow

Recruitment Details	Seventy-nine subjects met study inclusion criteria, and provided informed consent for participation in the study.
Pre-assignment Detail	Of 79 enrolled subjects, 44 developed signs of Alcohol Withdrawal Syndrome (AWS) sufficient to meet Diagnostic and Statistical Manual, 4th version, revised (DSMr-IV) criteria for AWS. These 44 were randomized to receive baclofen or placebo, in addition to benzodiazepine therapy. Of the 44 subjects randomized, 31 completed 72 hours of observation.

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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.	Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.
Period Title: Overall Study
STARTED	25	21
COMPLETED	18	13
NOT COMPLETED	7	8

Baseline Characteristics

Arm/Group Title	Baclofen	Placebo	Total
Arm/Group Description	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.	Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.	Total of all reporting groups
Overall Participants	25	19	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 96%	18 94.7%	42 95.5%
>=65 years	1 4%	1 5.3%	2 4.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.5 (10.3)	46.1 (11.9)	46.9 (10.9)
Sex: Female, Male (Count of Participants)
Female	6 24%	1 5.3%	7 15.9%
Male	19 76%	18 94.7%	37 84.1%
Region of Enrollment (participants) [Number]
United States	25 100%	19 100%	44 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen	Placebo
Arm/Group Description	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.	Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.
Measure Participants	25	21
Mean (Standard Deviation) [mg of benzodiazepine per 8 hours]	14.1 (8.9)	124.4 (290.3)

Adverse Events

Arm/Group Title	Baclofen		Placebo
Arm/Group Description	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.		Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.
All Cause Mortality
	Baclofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Baclofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/25 (8%)		1/19 (5.3%)
General disorders
Rapid progression of complications of alcoholism	2/25 (8%)	2	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Baclofen		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.