Acamprosate to Reduce Symptoms of Alcohol Withdrawal

• ClinicalTrials.gov Identifier: NCT00106106
• Recruitment Status: Completed
• First Posted: March 21, 2005
• Results First Posted: January 5, 2012
• Last Update Posted: January 12, 2012
• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): Markus Heilig, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Conditions: Alcohol-Related Disorders; Alcohol Dependence; Alcoholism; Healthy Volunteer
• Interventions: Procedure: NMR-spectroscopy; Drug: Oral acamprosate
• Enrollment: 56

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Acamprosate
Arm/Group Description	For subjects randomized to placebo control, placebo doses were given every 8 hours.	For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study.
Period Title: Overall Study
Started	26	23
Completed Both MRS Scans	18	15
Completed	22 [1]	19 [2]
Not Completed	4	4
[1] Although 22 subjects completed all other assessments for the study, only 18 completed both MRS scans; [2] Although 19 subjects completed all other assessments for the study, only 15 completed both MRS scans

Baseline Characteristics

Arm/Group Title		Placebo	Acamprosate	Total
Arm/Group Description		For subjects randomized to placebo control, placebo doses were given every 8 hours.	For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study.	Total of all reporting groups
Overall Number of Baseline Participants		26	23	49
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	23 participants	49 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	26 100.0%	23 100.0%	49 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants	23 participants	49 participants
		35.1 (6.1)	35.0 (5.8)	35.1 (6.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	23 participants	49 participants
	Female	11 42.3%	8 34.8%	19 38.8%
	Male	15 57.7%	15 65.2%	30 61.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	26 participants	23 participants	49 participants
		26	23	49

Outcome Measures

1. Primary Outcome

Title	Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 4
Description	The ratio of glutamate to creatine was determined using magnetic resonance spectroscopy (MRS), a technique that complements magnetic resonance imaging (MRI). MRS is used to determine the concentration of brain metabolites, such as glutamate, in brain tissue. MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

The analysis of participants was per protocol, i.e., all subjects who completed two MRS scans(Day 4 and Day 25) and for whom there were two measures of the glutamate/creatine ratio

Arm/Group Title	Placebo	Acamprosate
Arm/Group Description:	For subjects randomized to placebo control, placebo doses were given every 8 hours.	For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study.
Overall Number of Participants Analyzed	18	15
Mean (Standard Error); Unit of Measure: Ratio of glutamate to creatine
	1.256772 (0.038924)	1.294178 (0.043249)

2. Primary Outcome

Title	Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 25
Description	The ratio of glutamate to creatine was determined using magnetic resonance spectroscopy (MRS), a technique that complements magnetic resonance imaging (MRI). MRS is used to determine the concentration of brain metabolites, such as glutamate, in brain tissue. MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined.
Time Frame	Day 25

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Acamprosate
Arm/Group Description:	For subjects randomized to placebo control, placebo doses were given every 8 hours.	For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study.
Overall Number of Participants Analyzed	18	15
Mean (Standard Error); Unit of Measure: Ratio of glutamate to creatine
	1.350375 (0.044497)	1.166667 (0.049441)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo		Acamprosate
Arm/Group Description	For subjects randomized to placebo control, placebo doses were given every 8 hours.		For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study.
All-Cause Mortality
	Placebo		Acamprosate
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Placebo		Acamprosate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0.00%)		1/23 (4.35%)
General disorders
Vaso-vagal faint [1]	0/26 (0.00%)	0	1/23 (4.35%)	1
[1] Following an uneventful lumbar puncture and a brief smoking break, the female patient felt faint when she sat down to eat. A nurse had her lie down on the floor until she recovered.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Acamprosate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/22 (90.91%)		18/19 (94.74%)
Gastrointestinal disorders
Diarrhea †	3/22 (13.64%)		6/19 (31.58%)
Lack of appetite †	3/22 (13.64%)		7/19 (36.84%)
Nausea †	2/22 (9.09%)		3/19 (15.79%)
Vomiting †	1/22 (4.55%)		2/19 (10.53%)
General disorders
Headaches †	7/22 (31.82%)		12/19 (63.16%)
Lack of energy †	7/22 (31.82%)		10/19 (52.63%)
Stomach aches †	2/22 (9.09%)		8/19 (42.11%)
Musculoskeletal and connective tissue disorders
Muscle spasms †	5/22 (22.73%)		3/19 (15.79%)
Nervous system disorders
Abnormal Dreaming †	11/22 (50.00%)		11/19 (57.89%)
Anxiety †	9/22 (40.91%)		12/19 (63.16%)
Decreased interest in sex †	6/22 (27.27%)		6/19 (31.58%)
Dizziness †	5/22 (22.73%)		6/19 (31.58%)
Feeling Down †	9/22 (40.91%)		11/19 (57.89%)
Impaired concentration †	7/22 (31.82%)		7/19 (36.84%)
Mood swings †	9/22 (40.91%)		13/19 (68.42%)
Nervousness †	7/22 (31.82%)		10/19 (52.63%)
Sensation of prickling or tingling on the skin †	6/22 (27.27%)		2/19 (10.53%)
Shakiness †	3/22 (13.64%)		7/19 (36.84%)
Sleepiness †	15/22 (68.18%)		13/19 (68.42%)
Sleeplessness †	10/22 (45.45%)		12/19 (63.16%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Markus A. Heilig, M.D., Ph.D.
• Organization: NIH/National Institute on Alcohol Abuse and Alcoholism
• Phone: 301-435-9386
• EMail: mheilig@mail.nih.gov

Publications:

Daeppen JB, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, Yersin B. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002 May 27;162(10):1117-21. doi: 10.1001/archinte.162.10.1117.

Liskow BI, Goodwin DW. Pharmacological treatment of alcohol intoxication, withdrawal and dependence: a critical review. J Stud Alcohol. 1987 Jul;48(4):356-70. doi: 10.15288/jsa.1987.48.356.

Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997 Jul 9;278(2):144-51. doi: 10.1001/jama.278.2.144.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vatsalya V, Cave MC, Kumar R, Srivastava S, Khanal S, Jenson AB, Schwandt ML, Barve SS, Ramchandani VA, McClain CJ. Alterations in Serum Zinc and Polyunsaturated Fatty Acid Concentrations in Treatment-Naive HIV-Diagnosed Alcohol-Dependent Subjects with Liver Injury. AIDS Res Hum Retroviruses. 2019 Jan;35(1):92-99. doi: 10.1089/AID.2018.0124. Epub 2018 Dec 11.

Vatsalya V, Kong M, Cave MC, Liu N, Schwandt ML, George DT, Ramchandani VA, McClain CJ. Association of serum zinc with markers of liver injury in very heavy drinking alcohol-dependent patients. J Nutr Biochem. 2018 Sep;59:49-55. doi: 10.1016/j.jnutbio.2018.05.003. Epub 2018 May 12.

Umhau JC, Momenan R, Schwandt ML, Singley E, Lifshitz M, Doty L, Adams LJ, Vengeliene V, Spanagel R, Zhang Y, Shen J, George DT, Hommer D, Heilig M. Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study. Arch Gen Psychiatry. 2010 Oct;67(10):1069-77. doi: 10.1001/archgenpsychiatry.2010.125.

• Responsible Party: Markus Heilig, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• ClinicalTrials.gov Identifier: NCT00106106
• Other Study ID Numbers: 050120; 05-AA-0120 ( Other Identifier: National Institutes of Health )
• First Submitted: March 19, 2005
• First Posted: March 21, 2005
• Results First Submitted: November 30, 2011
• Results First Posted: January 5, 2012
• Last Update Posted: January 12, 2012