Biomarker Study of Acamprosate in Schizophrenia

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT00688324
• Collaborator: National Alliance for Research on Schizophrenia and Depression (Other), National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 36
• Locations: 4
• Arm: 1
• Actual Duration (Months): 44
• Patients Per Site: 9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

NMDA receptors are brain receptors that are stimulated by glutamate. Poorly functioning NMDA receptors are thought to be involved in the pathology of schizophrenia. This hypothesis is based on the observation that PCP, which blocks the NMDA receptor, produces symptoms and cognitive impairments similar to schizophrenia. Efforts to enhance the function of the NMDA receptor with glycine and D-cycloserine have met with limited success. An alternative approach would be to use the drug acamprosate.

Acamprosate, FDA-approved for maintenance of sobriety after detoxification from alcohol, seems to act through modulation of the NMDA receptor. In the lab, acamprosate has been noted to act as an antagonist when the NMDA receptors are maximally stimulated but as an agonist when NMDA receptor stimulation is minimal. This "smart drug" action makes acamprosate appealing for use in schizophrenia. If acamprosate works as a smart drug in patients, then we would predict that it would enhance the function of NMDA receptors in schizophrenia and improve cognition and the symptoms of the illness. Additionally, acamprosate seems to modulate the NMDA receptor in novel ways distinct from glycine and D-cycloserine.

We will also see if the response to acamprosate differs based on whether participants do or do not have a past history of alcohol use disorders.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: Acamprosate	Phase 4

Detailed Description

We propose to measure the response of symptoms and cognition in people schizophrenia given acamprosate or placebo. We hypothesize that symptoms and cognition will improve following two weeks of acamprosate. We will also use proton magnetic resonance spectroscopy (MRS) to examine the effect of acamprosate on glutamate & glutamine (Glu&Gln) brain levels in people with schizophrenia. We hypothesize that Glu&Gln concentrations in people with chronic schizophrenia will increase following two weeks of treatment with acamprosate.

The proposed study will consist of 50 individuals with chronic schizophrenia/schizoaffective disorder, 18-55 years old, from in/outpatient programs at the Maryland Psychiatric Research Center (MPRC). The dose of acamprosate will follow manufacturer recommendations with two 333mg tablets given three times per day. MRS will be acquired from areas involved in schizophrenia [dorsolateral-prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)] at baseline and week two. Symptom ratings and cognitive testing will occur at baseline and be repeated at week two.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Biomarker Study of Acamprosate in Schizophrenia
• Actual Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm All subjects will have baseline measures, receive acamprosate for 2 weeks, then have measures repeated.	Drug: Acamprosate; Acamprosate 333mg, ii tablets PO tid x 2 weeks; Other Names: Campral

Outcome Measures

Primary Outcome Measures

1. Anterior Cingulate Cortex - Choline [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

2. Anterior Cingulate Cortex - Creatinine [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

3. Anterior Cingulate Cortex - Glutamate [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

4. Anterior Cingulate Cortex - N-acetylaspartate [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

5. Anterior Cingulate Cortex - Myo-inositol [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

6. Right Dorsal Lateral Prefrontal Cortex - Choline [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

7. Right Dorsal Lateral Prefrontal Cortex - Creatinine [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

8. Right Dorsal Lateral Prefrontal Cortex - Glutamate [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

9. Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

   N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

10. Right Dorsal Lateral Prefrontal Cortex - Myo-inositol [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

    Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

11. Left Dorsal Lateral Prefrontal Cortex - Choline [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

    Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

12. Left Dorsal Lateral Prefrontal Cortex - Creatinine [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

    Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

13. Left Dorsal Lateral Prefrontal Cortex - Glutamate [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

    Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

14. Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

    N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

15. Left Dorsal Lateral Prefrontal Cortex - Myo-inositol [Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)]

    Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".

16. Fractional Anisotropy Measured With Diffusion Tensor Imaging [Completion of two scans]

    Diffusion Tensor Imaging Frational Anisotropy (FA) Measures by Lifetime History of Alcohol Abuse/Dependence and Brain Hemisphere.

Secondary Outcome Measures

1. BPRS - Symptoms of Psychosis Change in Scores [Baseline (Treatment Week 0) and End of Study (Treatment Week 2)]

   Symptoms of psychosis were measured with the Brief Psychiatric Rating Scale (BPRS). The items rated for psychosis are "Conceptual Disorganization", "Suspiciousness", "Hallucinatory Behavior", and "Unusual Thought Content". Each item score ranges from "1=Not Present" to "7=Very Severe". Value at End of Study minus value at Baseline.

2. BPRS - Symptoms of Psychosis Total Score [Baseline (Treatment Week 0) and End of Study (Treatment Week 2)]

   The psychosis total score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating.

3. SANS - Negative Symptoms of Schizophrenia Total Score [Baseline (Treatment Week 0) and End of Study (Treatment Week 2)]

   Negative symptoms of schizophrenia measured using the Scale for the Assessment of Negative Symptoms (SANS) Total Score. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms.

4. Cognitive Impairment [Change from Baseline (Treatment Week 0) to End of Study (Treatment Week 2)]

   Cognitive tests will include the DigitSymbol Test (evaluating processing speed), California Verbal Learning Test (CVLT; evaluating verbal learning and episodic memory), and NBack (evaluating working memory). Digit Symbol scaled scores range from 1 to 19, with the larger numbers indicating better performance. On the CVLT, the delayed recognition score ranges from 0 to 16, with the larger numbers indicating better performance. On the NBack test, subjects were asked to recall items 0-back, 1-back, and 2-back in a sequence. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• DSM-IV diagnosis of schizophrenia/schizoaffective disorder

• Age 18-55 years

• Male or female

• Any Race/ethnicity

• Participants will be analyzed separately depending on whether they do or do not have a history of an alcohol use disorder

Exclusion Criteria:

• Pregnant/nursing females or females not using adequate birth control

• Documented history of mental retardation/severe neurological disorder/head injury with loss of consciousness

• DSM-IV diagnosis of substance dependence in previous six months/abuse in the previous three months (except nicotine)

• Serious suicidal risk in the previous six months

• History of renal failure/creatinine clearance of less than 50mL/min

• Current treatment with clozapine

• Contraindication to MRI scanning.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Maryland Health Care System	Baltimore	Maryland	United States	21201
2	Keypoint Community Mental Health Centers- Dundalk	Baltimore	Maryland	United States	21222
3	Keypoint Community Mental Health Centers- Catonsville	Baltimore	Maryland	United States	21228
4	Maryland Psychiatric Research Center	Baltimore	Maryland	United States	21228

Sponsors and Collaborators

• University of Maryland, Baltimore
• National Alliance for Research on Schizophrenia and Depression
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Bernard A Fischer, M.D., Food and Drug Administration (FDA)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Maryland Psychiatric Research Center

Publications

None provided.

• Responsible Party: Robert Buchanan, Chief, Maryland Psychiatric Research Center, Outpatient Research Program, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00688324
• Other Study ID Numbers: HP-00043248; R03AA019571
• First Posted: Jun 2, 2008
• Last Update Posted: Sep 25, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Robert Buchanan, Chief, Maryland Psychiatric Research Center, Outpatient Research Program, University of Maryland, Baltimore: schizophrenia; schizoaffective disorder; glutamate; NMDA receptor; magnetic resonance spectroscopy; acamprosate
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Acamprosate

Study Results

Participant Flow

Pre-assignment Detail	There were 39 subjects who signed consent for the study. Three subjects were excluded prior to entering the study: two subjects refused to continue and one subject was hospitalized. Thirty six subjects entered the first phase of the study.

Arm/Group Title	Single Arm
Arm/Group Description	All subjects will have baseline measures, receive acamprosate for 2 weeks, then have measures repeated. Acamprosate: Acamprosate 333mg, ii tablets PO tid x 2 weeks
Period Title: Overall Study
STARTED	36
COMPLETED	28
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Baseline Screening
Arm/Group Description	All subjects will have baseline measures
Overall Participants	36
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 77.8%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44 (9.2)
Sex: Female, Male (Count of Participants)
Female	11 30.6%
Male	25 69.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.6%
Not Hispanic or Latino	34 94.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.8%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	20 55.6%
White	12 33.3%
More than one race	3 8.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	36 100%
Alcohol Abuse History (participants) [Number]
Present	16 44.4%
Absent	18 50%
Missing	2 5.6%

Outcome Measures

1. Primary Outcome

Title	Anterior Cingulate Cortex - Choline
Description	Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	18
Scan 1	1.64 (0.20)	1.54 (0.26)
Scan 2	1.46 (0.18)	1.58 (0.26)
Difference	-0.10 (0.12)	0.04 (0.19)

2. Primary Outcome

Title	Anterior Cingulate Cortex - Creatinine
Description	Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	18
Scan 1	5.46 (0.61)	5.12 (0.81)
Scan 2	5.09 (0.54)	5.16 (0.74)
Difference	-0.14 (0.31)	0.07 (0.39)

3. Primary Outcome

Title	Anterior Cingulate Cortex - Glutamate
Description	Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	18
Scan 1	7.44 (0.65)	6.68 (1.86)
Scan 2	7.06 (0.78)	7.05 (2.02)
Difference	-0.25 (0.91)	0.26 (1.28)

4. Primary Outcome

Title	Anterior Cingulate Cortex - N-acetylaspartate
Description	N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	18
Scan 1	6.40 (0.52)	5.99 (1.11)
Scan 2	6.06 (0.59)	6.14 (0.86)
Difference	-0.23 (0.35)	0.15 (0.53)

5. Primary Outcome

Title	Anterior Cingulate Cortex - Myo-inositol
Description	Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	18
Scan 1	4.34 (0.53)	4.00 (1.34)
Scan 2	4.00 (0.67)	4.35 (0.81)
Difference	-0.17 (0.46)	0.20 (0.46)

6. Primary Outcome

Title	Right Dorsal Lateral Prefrontal Cortex - Choline
Description	Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	13	17
Scan 1	1.36 (0.29)	1.30 (0.29)
Scan 2	1.32 (0.17)	1.71 (1.11)
Difference	0.06 (0.16)	0.40 (1.20)

7. Primary Outcome

Title	Right Dorsal Lateral Prefrontal Cortex - Creatinine
Description	Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	15	17
Scan 1	5.51 (0.61)	5.48 (0.92)
Scan 2	5.52 (0.51)	5.54 (0.70)
Difference	0.27 (0.64)	0.11 (0.76)

8. Primary Outcome

Title	Right Dorsal Lateral Prefrontal Cortex - Glutamate
Description	Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	13	15
Scan 1	6.89 (1.10)	7.51 (2.00)
Scan 2	6.63 (1.03)	7.15 (0.92)
Difference	-0.44 (1.52)	-0.69 (1.90)

9. Primary Outcome

Title	Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate
Description	N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	15	17
Scan 1	7.43 (0.78)	7.65 (1.03)
Scan 2	7.65 (0.54)	8.15 (1.24)
Difference	0.35 (0.78)	0.42 (0.96)

10. Primary Outcome

Title	Right Dorsal Lateral Prefrontal Cortex - Myo-inositol
Description	Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	15	16
Scan 1	3.73 (0.72)	3.71 (0.43)
Scan 2	3.41 (0.43)	3.44 (0.68)
Difference	-0.17 (0.66)	-0.24 (0.76)

11. Primary Outcome

Title	Left Dorsal Lateral Prefrontal Cortex - Choline
Description	Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	15
Scan 1	1.53 (0.36)	1.53 (0.23)
Scan 2	1.57 (0.20)	1.65 (0.21)
Difference	0.05 (0.24)	0.10 (0.23)

12. Primary Outcome

Title	Left Dorsal Lateral Prefrontal Cortex - Creatinine
Description	Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	17	15
Scan 1	5.38 (0.84)	5.78 (0.64)
Scan 2	5.43 (1.13)	5.86 (0.53)
Difference	0.15 (0.82)	0.11 (0.55)

13. Primary Outcome

Title	Left Dorsal Lateral Prefrontal Cortex - Glutamate
Description	Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	13	14
Scan 1	7.45 (1.21)	6.98 (1.07)
Scan 2	6.86 (1.03)	6.92 (0.55)
Difference	-0.50 (1.36)	0.03 (1.32)

14. Primary Outcome

Title	Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate
Description	N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	14
Scan 1	7.22 (0.99)	7.50 (0.87)
Scan 2	7.44 (1.25)	8.04 (1.68)
Difference	0.25 (0.77)	0.16 (0.91)

15. Primary Outcome

Title	Left Dorsal Lateral Prefrontal Cortex - Myo-inositol
Description	Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Time Frame	Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Outcome Measure Data

Analysis Population Description

Usable scan data.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	15	14
Scan 1	3.69 (0.79)	3.61 (0.69)
Scan 2	3.34 (0.64)	4.08 (0.91)
Difference	-0.08 (0.97)	0.51 (0.72)

16. Primary Outcome

Title	Fractional Anisotropy Measured With Diffusion Tensor Imaging
Description	Diffusion Tensor Imaging Frational Anisotropy (FA) Measures by Lifetime History of Alcohol Abuse/Dependence and Brain Hemisphere.
Time Frame	Completion of two scans

Outcome Measure Data

Analysis Population Description

Subjects completing study (both scans).

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	13	15
Right hemisphere	0.63 (0.03)	0.61 (0.05)
Left hemisphere	0.59 (0.04)	0.57 (0.04)

17. Secondary Outcome

Title	BPRS - Symptoms of Psychosis Change in Scores
Description	Symptoms of psychosis were measured with the Brief Psychiatric Rating Scale (BPRS). The items rated for psychosis are "Conceptual Disorganization", "Suspiciousness", "Hallucinatory Behavior", and "Unusual Thought Content". Each item score ranges from "1=Not Present" to "7=Very Severe". Value at End of Study minus value at Baseline.
Time Frame	Baseline (Treatment Week 0) and End of Study (Treatment Week 2)

Outcome Measure Data

Analysis Population Description

Subjects completing the BPRS rating at Baseline and End of Study.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	11	16
Conceptual Disorganization Change	-0.182 (0.603)	0.0 (0.730)
Suspiciousness Change	-0.636 (2.111)	-0.532 (1.209)
Hallucinations Change	-0.0909 (1.7581)	-0.6250 (1.3102)
Unusual Thought Content Change	-0.0909 (1.1362)	-0.1250 (0.7188)

18. Secondary Outcome

Title	BPRS - Symptoms of Psychosis Total Score
Description	The psychosis total score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating.
Time Frame	Baseline (Treatment Week 0) and End of Study (Treatment Week 2)

Outcome Measure Data

Analysis Population Description

Subjects completing BPRS rating at each time point.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	17
Baseline	8.88 (3.77)	9.47 (4.45)
End of study	8.82 (4.14)	8.38 (4.16)
Change	-1.00 (3.95)	-1.31 (2.33)

19. Secondary Outcome

Title	SANS - Negative Symptoms of Schizophrenia Total Score
Description	Negative symptoms of schizophrenia measured using the Scale for the Assessment of Negative Symptoms (SANS) Total Score. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms.
Time Frame	Baseline (Treatment Week 0) and End of Study (Treatment Week 2)

Outcome Measure Data

Analysis Population Description

Subjects completing the SANS assessment at each time point.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	16	17
Baseline	23.50 (10.73)	26.12 (9.14)
End of study	24.18 (12.09)	26.38 (9.49)
Change	2.091 (8.384)	-0.375 (6.407)

20. Secondary Outcome

Title	Cognitive Impairment
Description	Cognitive tests will include the DigitSymbol Test (evaluating processing speed), California Verbal Learning Test (CVLT; evaluating verbal learning and episodic memory), and NBack (evaluating working memory). Digit Symbol scaled scores range from 1 to 19, with the larger numbers indicating better performance. On the CVLT, the delayed recognition score ranges from 0 to 16, with the larger numbers indicating better performance. On the NBack test, subjects were asked to recall items 0-back, 1-back, and 2-back in a sequence. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.
Time Frame	Change from Baseline (Treatment Week 0) to End of Study (Treatment Week 2)

Outcome Measure Data

Analysis Population Description

Subjects who completed cognitive testing at both study time points.

Arm/Group Title	ETOH Abuse	No ETOH Abuse
Arm/Group Description	Lifetime History of Alcohol Abuse/Dependence	No Lifetime History of Alcohol Abuse/Dependence
Measure Participants	11	14
Change in NBack 0-Back Total Hits	0.000 (1.886)	0.214 (1.188)
Change in NBack 1-Back Total Hits	0.60 (3.20)	1.14 (3.42)
Change in NBack 2-Back Total Hits	1.70 (2.41)	1.71 (3.27)
Change in DigitSymbol Scaled Score	-0.20 (1.03)	0.00 (1.30)
Change in CVLT Total Recall	-0.600 (1.955)	-0.143 (1.956)

Adverse Events

Time Frame	Overall study of 6 weeks.
Adverse Event Reporting Description	Reportable adverse events (AEs) are defined as any harm experienced by a study participant, which in the opinion of the investigator is unexpected and probably related to the research procedures. None of our AEs met these criteria. Participants are systematically monitored for any increases the Side Effects Checklist (SEC). An SEC AE includes any symptom/side effect rated with a score of 4 (severe) or for which there was a 2 point change in severity from baseline.
Arm/Group Title	Single Arm
Arm/Group Description	All subjects will have baseline measures, receive acamprosate for 2 weeks, then have measures repeated. Acamprosate: Acamprosate 333mg, ii tablets PO tid x 2 weeks
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	6/36 (16.7%)
Gastrointestinal disorders
Diarrhea	3/36 (8.3%)	3
General disorders
Insomnia	1/36 (2.8%)	1
Restlessness	1/36 (2.8%)	1
Musculoskeletal and connective tissue disorders
Stiffness	1/36 (2.8%)	1
Nervous system disorders
Perceived increase in essential tremor	1/36 (2.8%)	1
Psychiatric disorders
Claustrophobia in MRI scan	1/36 (2.8%)	1

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.