Trial Outcomes & Findings for Biomarker Study of Acamprosate in Schizophrenia (NCT NCT00688324)

NCT ID: NCT00688324

Last Updated: 2019-09-25

Results Overview

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".

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

36 participants

Primary outcome timeframe

Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Results posted on

2019-09-25

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Single Arm 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
Overall Study STARTED	36
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Single Arm 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
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	5
Overall Study Lost to Follow-up	1

Baseline Characteristics

Date of birth was not recorded for eight participants who gave consent for screening but did not complete the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Baseline Screening n=36 Participants All subjects will have baseline measures
Age, Categorical <=18 years	0 Participants n=28 Participants • Date of birth was not recorded for eight participants who gave consent for screening but did not complete the study.
Age, Categorical Between 18 and 65 years	28 Participants n=28 Participants • Date of birth was not recorded for eight participants who gave consent for screening but did not complete the study.
Age, Categorical >=65 years	0 Participants n=28 Participants • Date of birth was not recorded for eight participants who gave consent for screening but did not complete the study.
Age, Continuous	44 years STANDARD_DEVIATION 9.2 • n=28 Participants • Date of birth was not recorded for eight participants who gave consent for screening but did not complete the study.
Sex: Female, Male Female	11 Participants n=36 Participants
Sex: Female, Male Male	25 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	20 Participants n=36 Participants
Race (NIH/OMB) White	12 Participants n=36 Participants
Race (NIH/OMB) More than one race	3 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=36 Participants
Region of Enrollment United States	36 participants n=36 Participants
Alcohol Abuse History Present	16 participants n=36 Participants
Alcohol Abuse History Absent	18 participants n=36 Participants
Alcohol Abuse History Missing	2 participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

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

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=18 Participants No Lifetime History of Alcohol Abuse/Dependence
Anterior Cingulate Cortex - Choline Scan 1	1.64 mM Standard Deviation 0.20	1.54 mM Standard Deviation 0.26
Anterior Cingulate Cortex - Choline Scan 2	1.46 mM Standard Deviation 0.18	1.58 mM Standard Deviation 0.26
Anterior Cingulate Cortex - Choline Difference	-0.10 mM Standard Deviation 0.12	0.04 mM Standard Deviation 0.19

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

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

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=18 Participants No Lifetime History of Alcohol Abuse/Dependence
Anterior Cingulate Cortex - Creatinine Scan 1	5.46 mM Standard Deviation 0.61	5.12 mM Standard Deviation 0.81
Anterior Cingulate Cortex - Creatinine Scan 2	5.09 mM Standard Deviation 0.54	5.16 mM Standard Deviation 0.74
Anterior Cingulate Cortex - Creatinine Difference	-0.14 mM Standard Deviation 0.31	0.07 mM Standard Deviation 0.39

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

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

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=18 Participants No Lifetime History of Alcohol Abuse/Dependence
Anterior Cingulate Cortex - Glutamate Scan 1	7.44 mM Standard Deviation 0.65	6.68 mM Standard Deviation 1.86
Anterior Cingulate Cortex - Glutamate Scan 2	7.06 mM Standard Deviation 0.78	7.05 mM Standard Deviation 2.02
Anterior Cingulate Cortex - Glutamate Difference	-0.25 mM Standard Deviation 0.91	0.26 mM Standard Deviation 1.28

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

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

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=18 Participants No Lifetime History of Alcohol Abuse/Dependence
Anterior Cingulate Cortex - N-acetylaspartate Scan 1	6.40 mM Standard Deviation 0.52	5.99 mM Standard Deviation 1.11
Anterior Cingulate Cortex - N-acetylaspartate Scan 2	6.06 mM Standard Deviation 0.59	6.14 mM Standard Deviation 0.86
Anterior Cingulate Cortex - N-acetylaspartate Difference	-0.23 mM Standard Deviation 0.35	0.15 mM Standard Deviation 0.53

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

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

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=18 Participants No Lifetime History of Alcohol Abuse/Dependence
Anterior Cingulate Cortex - Myo-inositol Scan 1	4.34 mM Standard Deviation 0.53	4.00 mM Standard Deviation 1.34
Anterior Cingulate Cortex - Myo-inositol Scan 2	4.00 mM Standard Deviation 0.67	4.35 mM Standard Deviation 0.81
Anterior Cingulate Cortex - Myo-inositol Difference	-0.17 mM Standard Deviation 0.46	0.20 mM Standard Deviation 0.46

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=13 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=17 Participants No Lifetime History of Alcohol Abuse/Dependence
Right Dorsal Lateral Prefrontal Cortex - Choline Scan 1	1.36 mM Standard Deviation 0.29	1.30 mM Standard Deviation 0.29
Right Dorsal Lateral Prefrontal Cortex - Choline Scan 2	1.32 mM Standard Deviation 0.17	1.71 mM Standard Deviation 1.11
Right Dorsal Lateral Prefrontal Cortex - Choline Difference	0.06 mM Standard Deviation 0.16	0.40 mM Standard Deviation 1.20

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=15 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=17 Participants No Lifetime History of Alcohol Abuse/Dependence
Right Dorsal Lateral Prefrontal Cortex - Creatinine Scan 1	5.51 mM Standard Deviation 0.61	5.48 mM Standard Deviation 0.92
Right Dorsal Lateral Prefrontal Cortex - Creatinine Scan 2	5.52 mM Standard Deviation 0.51	5.54 mM Standard Deviation 0.70
Right Dorsal Lateral Prefrontal Cortex - Creatinine Difference	0.27 mM Standard Deviation 0.64	0.11 mM Standard Deviation 0.76

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=13 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=15 Participants No Lifetime History of Alcohol Abuse/Dependence
Right Dorsal Lateral Prefrontal Cortex - Glutamate Scan 1	6.89 mM Standard Deviation 1.10	7.51 mM Standard Deviation 2.00
Right Dorsal Lateral Prefrontal Cortex - Glutamate Scan 2	6.63 mM Standard Deviation 1.03	7.15 mM Standard Deviation 0.92
Right Dorsal Lateral Prefrontal Cortex - Glutamate Difference	-0.44 mM Standard Deviation 1.52	-0.69 mM Standard Deviation 1.90

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=15 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=17 Participants No Lifetime History of Alcohol Abuse/Dependence
Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate Scan 1	7.43 mM Standard Deviation 0.78	7.65 mM Standard Deviation 1.03
Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate Scan 2	7.65 mM Standard Deviation 0.54	8.15 mM Standard Deviation 1.24
Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate Difference	0.35 mM Standard Deviation 0.78	0.42 mM Standard Deviation 0.96

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=15 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=16 Participants No Lifetime History of Alcohol Abuse/Dependence
Right Dorsal Lateral Prefrontal Cortex - Myo-inositol Scan 1	3.73 mM Standard Deviation 0.72	3.71 mM Standard Deviation 0.43
Right Dorsal Lateral Prefrontal Cortex - Myo-inositol Scan 2	3.41 mM Standard Deviation 0.43	3.44 mM Standard Deviation 0.68
Right Dorsal Lateral Prefrontal Cortex - Myo-inositol Difference	-0.17 mM Standard Deviation 0.66	-0.24 mM Standard Deviation 0.76

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=15 Participants No Lifetime History of Alcohol Abuse/Dependence
Left Dorsal Lateral Prefrontal Cortex - Choline Scan 1	1.53 mM Standard Deviation 0.36	1.53 mM Standard Deviation 0.23
Left Dorsal Lateral Prefrontal Cortex - Choline Scan 2	1.57 mM Standard Deviation 0.20	1.65 mM Standard Deviation 0.21
Left Dorsal Lateral Prefrontal Cortex - Choline Difference	0.05 mM Standard Deviation 0.24	0.10 mM Standard Deviation 0.23

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=17 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=15 Participants No Lifetime History of Alcohol Abuse/Dependence
Left Dorsal Lateral Prefrontal Cortex - Creatinine Scan 1	5.38 mM Standard Deviation 0.84	5.78 mM Standard Deviation 0.64
Left Dorsal Lateral Prefrontal Cortex - Creatinine Scan 2	5.43 mM Standard Deviation 1.13	5.86 mM Standard Deviation 0.53
Left Dorsal Lateral Prefrontal Cortex - Creatinine Difference	0.15 mM Standard Deviation 0.82	0.11 mM Standard Deviation 0.55

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=13 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=14 Participants No Lifetime History of Alcohol Abuse/Dependence
Left Dorsal Lateral Prefrontal Cortex - Glutamate Scan 1	7.45 mM Standard Deviation 1.21	6.98 mM Standard Deviation 1.07
Left Dorsal Lateral Prefrontal Cortex - Glutamate Scan 2	6.86 mM Standard Deviation 1.03	6.92 mM Standard Deviation 0.55
Left Dorsal Lateral Prefrontal Cortex - Glutamate Difference	-0.50 mM Standard Deviation 1.36	0.03 mM Standard Deviation 1.32

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=14 Participants No Lifetime History of Alcohol Abuse/Dependence
Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate Scan 1	7.22 mM Standard Deviation 0.99	7.50 mM Standard Deviation 0.87
Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate Scan 2	7.44 mM Standard Deviation 1.25	8.04 mM Standard Deviation 1.68
Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate Difference	0.25 mM Standard Deviation 0.77	0.16 mM Standard Deviation 0.91

PRIMARY outcome

Timeframe: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)

Population: Usable scan data.

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".

Outcome measures

Outcome measures
Measure	ETOH Abuse n=15 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=14 Participants No Lifetime History of Alcohol Abuse/Dependence
Left Dorsal Lateral Prefrontal Cortex - Myo-inositol Scan 1	3.69 mM Standard Deviation 0.79	3.61 mM Standard Deviation 0.69
Left Dorsal Lateral Prefrontal Cortex - Myo-inositol Scan 2	3.34 mM Standard Deviation 0.64	4.08 mM Standard Deviation 0.91
Left Dorsal Lateral Prefrontal Cortex - Myo-inositol Difference	-0.08 mM Standard Deviation 0.97	0.51 mM Standard Deviation 0.72

PRIMARY outcome

Timeframe: Completion of two scans

Population: Subjects completing study (both scans).

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

Outcome measures

Outcome measures
Measure	ETOH Abuse n=13 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=15 Participants No Lifetime History of Alcohol Abuse/Dependence
Fractional Anisotropy Measured With Diffusion Tensor Imaging Right hemisphere	0.63 FA Standard Deviation 0.03	0.61 FA Standard Deviation 0.05
Fractional Anisotropy Measured With Diffusion Tensor Imaging Left hemisphere	0.59 FA Standard Deviation 0.04	0.57 FA Standard Deviation 0.04

SECONDARY outcome

Timeframe: Baseline (Treatment Week 0) and End of Study (Treatment Week 2)

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

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.

Outcome measures

Outcome measures
Measure	ETOH Abuse n=11 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=16 Participants No Lifetime History of Alcohol Abuse/Dependence
BPRS - Symptoms of Psychosis Change in Scores Conceptual Disorganization Change	-0.182 units on a scale Standard Deviation 0.603	0.0 units on a scale Standard Deviation 0.730
BPRS - Symptoms of Psychosis Change in Scores Suspiciousness Change	-0.636 units on a scale Standard Deviation 2.111	-0.532 units on a scale Standard Deviation 1.209
BPRS - Symptoms of Psychosis Change in Scores Hallucinations Change	-0.0909 units on a scale Standard Deviation 1.7581	-0.6250 units on a scale Standard Deviation 1.3102
BPRS - Symptoms of Psychosis Change in Scores Unusual Thought Content Change	-0.0909 units on a scale Standard Deviation 1.1362	-0.1250 units on a scale Standard Deviation 0.7188

SECONDARY outcome

Timeframe: Baseline (Treatment Week 0) and End of Study (Treatment Week 2)

Population: Subjects completing BPRS rating at each time point.

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.

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=17 Participants No Lifetime History of Alcohol Abuse/Dependence
BPRS - Symptoms of Psychosis Total Score Baseline	8.88 units on a scale Standard Deviation 3.77	9.47 units on a scale Standard Deviation 4.45
BPRS - Symptoms of Psychosis Total Score End of study	8.82 units on a scale Standard Deviation 4.14	8.38 units on a scale Standard Deviation 4.16
BPRS - Symptoms of Psychosis Total Score Change	-1.00 units on a scale Standard Deviation 3.95	-1.31 units on a scale Standard Deviation 2.33

SECONDARY outcome

Timeframe: Baseline (Treatment Week 0) and End of Study (Treatment Week 2)

Population: Subjects completing the SANS assessment at each time point.

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.

Outcome measures

Outcome measures
Measure	ETOH Abuse n=16 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=17 Participants No Lifetime History of Alcohol Abuse/Dependence
SANS - Negative Symptoms of Schizophrenia Total Score Baseline	23.50 units on a scale Standard Deviation 10.73	26.12 units on a scale Standard Deviation 9.14
SANS - Negative Symptoms of Schizophrenia Total Score End of study	24.18 units on a scale Standard Deviation 12.09	26.38 units on a scale Standard Deviation 9.49
SANS - Negative Symptoms of Schizophrenia Total Score Change	2.091 units on a scale Standard Deviation 8.384	-0.375 units on a scale Standard Deviation 6.407

SECONDARY outcome

Timeframe: Change from Baseline (Treatment Week 0) to End of Study (Treatment Week 2)

Population: Subjects who completed cognitive testing at both study time points.

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.

Outcome measures

Outcome measures
Measure	ETOH Abuse n=11 Participants Lifetime History of Alcohol Abuse/Dependence	No ETOH Abuse n=14 Participants No Lifetime History of Alcohol Abuse/Dependence
Cognitive Impairment Change in NBack 0-Back Total Hits	0.000 units on a scale Standard Deviation 1.886	0.214 units on a scale Standard Deviation 1.188
Cognitive Impairment Change in NBack 1-Back Total Hits	0.60 units on a scale Standard Deviation 3.20	1.14 units on a scale Standard Deviation 3.42
Cognitive Impairment Change in NBack 2-Back Total Hits	1.70 units on a scale Standard Deviation 2.41	1.71 units on a scale Standard Deviation 3.27
Cognitive Impairment Change in DigitSymbol Scaled Score	-0.20 units on a scale Standard Deviation 1.03	0.00 units on a scale Standard Deviation 1.30
Cognitive Impairment Change in CVLT Total Recall	-0.600 units on a scale Standard Deviation 1.955	-0.143 units on a scale Standard Deviation 1.956

Adverse Events

Single Arm

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Single Arm n=36 participants at risk 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
Nervous system disorders Perceived increase in essential tremor	2.8% 1/36 • Number of events 1 • Overall study of 6 weeks. 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.
Psychiatric disorders Claustrophobia in MRI scan	2.8% 1/36 • Number of events 1 • Overall study of 6 weeks. 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.
Gastrointestinal disorders Diarrhea	8.3% 3/36 • Number of events 3 • Overall study of 6 weeks. 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.
General disorders Insomnia	2.8% 1/36 • Number of events 1 • Overall study of 6 weeks. 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.
General disorders Restlessness	2.8% 1/36 • Number of events 1 • Overall study of 6 weeks. 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.
Musculoskeletal and connective tissue disorders Stiffness	2.8% 1/36 • Number of events 1 • Overall study of 6 weeks. 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.

Additional Information

Robert W. Buchanan, M.D.

Maryland Psychiatric Research Center

Phone: 410-402-7876

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place