Treatment With Acamprosate in Patients With Schizophrenia and Comorbid Alcoholism

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00463346
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 106
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The aim of this study is to evaluate the safety and efficacy of acamprosate for patients with alcohol dependence and comorbid schizophrenia spectrum disorders.

• 1: Relative to placebo, acamprosate will significantly increase cumulative days of abstinence in recently detoxified alcohol dependent schizophrenia patients measured by Timeline Follow-Back (TLFB) method.

• 2: Acamprosate will have no significant effect on the psychotic symptoms in schizophrenia patients with alcohol dependence as measured by the Positive and Negative Syndrome Scale (PANSS).

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence; Schizophrenia	Drug: Acamprosate; Drug: Placebo	Phase 3

Detailed Description

Alcohol use disorders (AUD) are common comorbid conditions in patients with schizophrenia, and they cause a negative impact on the expression and course of schizophrenia. Improvements have been reported after attaining abstinence from alcohol, suggesting that effective treatments for AUD lead to clinically meaningful results. Acamprosate is a recently approved treatment for alcoholism, and it may be advantageous over other treatments since is not metabolized in the liver, and it has been used safely with other psychotropic medications. Therefore, acamprosate would be a promising treatment in schizophrenia patients. However, there are only few reports in the current literature evaluating the efficacy of medications available for the treatment of alcoholism in patients with schizophrenia, and the efficacy and safety of acamprosate have never been studied in this vulnerable group of patients.

Research Design:

This is a 12-week, randomized, double blind, placebo controlled trial of acamprosate (666 mg tid) in addition to neuroleptics in 30 recently abstinent (>5 days) schizophrenia patients with comorbid alcohol dependence.

Methods:

The study will be conducted at the West Haven, CT VA with support from Forest Laboratories. Patients who are between 21 and 65, with a diagnosis of schizophrenia spectrum disorder, (on stable psychotropic treatment > 2 weeks) and with current alcohol dependence (>1 recent episode of heavy drinking) will be included. Patients will be willing to undergo detoxification or self discontinuation >2weeks prior to the randomization. Main outcome variables include the TLFB method to document the degree of daily alcohol consumption, and PANSS, to assess the psychotic symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Treatment With Acamprosate in Patients With Schizophrenia and Comorbid Alcoholism
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acamprosate Acamprosate	Drug: Acamprosate; Acamprosate 1998 mg tid; Other Names: Campral
Placebo Comparator: placebo placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Drinking Days [12 weeks]

2. Psychotic Symptoms - Measured Using the PANSS [12 weeks]

   The PANSS or the Positive and Negative Syndrome Scale is a medical scale used for measuring symptom severity of patients with schizophrenia. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. Of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale.The scores for these scales are arrived at by summation of ratings across component items. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. A higher score indicates more severe symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Men and women between 21 and 65 years of age.

2. Patients with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder NOS as determined by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) [22].

3. Patients who are on stable treatment with psychotropic medication > 2 weeks prior to randomization.

4. Patients with current alcohol dependence, with at least one recent episode of heavy drinking (defined as 5 or more drinks per drinking episode) over the past 21 days, and willing to undergo detoxification or self discontinuation (for at least 5 days).

5. Patients, who are able to comprehend and satisfactorily comply with protocol requirements.

6. Patients who have capacity to provide informed consent prior to entering any study procedure.

Exclusion Criteria

1. Patients with dementia, amnestic and other cognitive disorders.

2. Patients who have unstable medical disease or a medical condition that, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial

3. Patients with a history of opioid dependence within the past month.

4. Patients with a history of intolerance or hypersensitivity to acamprosate.

5. Patients who are currently taking disulfiram or naltrexone.

6. Patients who based on history or mental status examination are at a significant risk for suicide.

7. Patients who are homicidal or violent and who are in the Investigator's opinion in significant imminent risk of hurting others.

8. Women who are pregnant or nursing, or women of childbearing potential who are sexually active and who do not use adequate contraception, or who are judged to be unreliable in their use of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Connecticut Healthcare System	West Haven	Connecticut	United States	06516

Sponsors and Collaborators

• Yale University
• Forest Laboratories

Investigators

• Principal Investigator: Ismene L Petrakis, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00463346
• Other Study ID Numbers: 0607001674; 0607001674; IP00027
• First Posted: Apr 20, 2007
• Last Update Posted: Mar 31, 2020
• Last Verified: Dec 1, 2015

• Keywords provided by Yale University: Treatment; Alcohol Dependence; Schizophrenia
• Additional relevant MeSH terms: Alcoholism; Schizophrenia; Acamprosate

Study Results

Participant Flow

Arm/Group Title	Acamprosate	Placebo
Arm/Group Description	Acamprosate 1998 mg TID dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.	dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.
Period Title: Overall Study
STARTED	12	11
COMPLETED	9	8
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Acamprosate	Placebo	Total
Arm/Group Description	Acamprosate 1998 mg TID dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.	Placebo dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.	Total of all reporting groups
Overall Participants	12	11	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	11 100%	23 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.27 (9.24)	49.18 (4.64)	50.73 (7.31)
Sex: Female, Male (Count of Participants)
Female	12 100%	7 63.6%	19 82.6%
Male	0 0%	4 36.4%	4 17.4%

Outcome Measures

1. Primary Outcome

Title	Number of Drinking Days
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acamprosate	Placebo
Arm/Group Description	Acamprosate 1998 mg TID Study medication was dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.	Placebo Study medication was dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.
Measure Participants	12	11
Mean (Standard Deviation) [days]	10.7 (17.11)	7.6 (11.5)

2. Primary Outcome

Title	Psychotic Symptoms - Measured Using the PANSS
Description	The PANSS or the Positive and Negative Syndrome Scale is a medical scale used for measuring symptom severity of patients with schizophrenia. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. Of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale.The scores for these scales are arrived at by summation of ratings across component items. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. A higher score indicates more severe symptoms.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acamprosate	Placebo
Arm/Group Description	Acamprosate Acamprosate: Acamprosate 1998 mg tid. Study medication was dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.	placebo Study medication was dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.
Measure Participants	12	11
PANSS positive symptoms	14.514 (1.263)	14.362 (1.352)
PANSS negative symptoms	13.476 (1.388)	15.971 (1.790)
PANSS general symptoms	28.083 (2.179)	29.33 (2.345)

Adverse Events

Arm/Group Title	Acamprosate		Placebo
Arm/Group Description	Acamprosate 1998 mg tid. Study medication was dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.		placebo Study medication was dispensed weekly in blister packs, labeled with the date and time, in identical looking capsules.
All Cause Mortality
	Acamprosate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Acamprosate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		1/11 (9.1%)
General disorders
Hospitalized for fainting and vomiting	0/12 (0%)	0	1/11 (9.1%)	1
Nervous system disorders
Seizure	0/12 (0%)	0	1/11 (9.1%)	1
Psychiatric disorders
Hospitalization for psychiatric symptoms	1/12 (8.3%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Acamprosate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.