Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
schizophrenia, schizoaffective disorder, glutamate, NMDA receptor, magnetic resonance spectroscopy, acamprosate
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.
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.
Interventions
DRUGAcamprosate
Acamprosate 333mg, ii tablets PO tid x 2 weeks
Sponsors
National Alliance for Research on Schizophrenia and Depression
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Baseline Screening All subjects will have baseline measures | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Baseline Screening |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 44 years STANDARD_DEVIATION 9.2 |
| Alcohol Abuse History Absent | 18 participants |
| Alcohol Abuse History Missing | 2 participants |
| Alcohol Abuse History Present | 16 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 36 |
| serious Total, serious adverse events | 0 / 36 |
Outcome results
Primary
Anterior Cingulate Cortex - Choline
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)
Population: Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Anterior Cingulate Cortex - Choline | Scan 1 | 1.64 mM | Standard Deviation 0.2 |
| ETOH Abuse | Anterior Cingulate Cortex - Choline | Scan 2 | 1.46 mM | Standard Deviation 0.18 |
| ETOH Abuse | Anterior Cingulate Cortex - Choline | Difference | -0.10 mM | Standard Deviation 0.12 |
| No ETOH Abuse | Anterior Cingulate Cortex - Choline | Scan 1 | 1.54 mM | Standard Deviation 0.26 |
| No ETOH Abuse | Anterior Cingulate Cortex - Choline | Scan 2 | 1.58 mM | Standard Deviation 0.26 |
| No ETOH Abuse | Anterior Cingulate Cortex - Choline | Difference | 0.04 mM | Standard Deviation 0.19 |
Primary
Anterior Cingulate Cortex - Creatinine
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)
Population: Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Anterior Cingulate Cortex - Creatinine | Scan 1 | 5.46 mM | Standard Deviation 0.61 |
| ETOH Abuse | Anterior Cingulate Cortex - Creatinine | Scan 2 | 5.09 mM | Standard Deviation 0.54 |
| ETOH Abuse | Anterior Cingulate Cortex - Creatinine | Difference | -0.14 mM | Standard Deviation 0.31 |
| No ETOH Abuse | Anterior Cingulate Cortex - Creatinine | Scan 1 | 5.12 mM | Standard Deviation 0.81 |
| No ETOH Abuse | Anterior Cingulate Cortex - Creatinine | Scan 2 | 5.16 mM | Standard Deviation 0.74 |
| No ETOH Abuse | Anterior Cingulate Cortex - Creatinine | Difference | 0.07 mM | Standard Deviation 0.39 |
Primary
Anterior Cingulate Cortex - Glutamate
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)
Population: Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Anterior Cingulate Cortex - Glutamate | Scan 2 | 7.06 mM | Standard Deviation 0.78 |
| ETOH Abuse | Anterior Cingulate Cortex - Glutamate | Difference | -0.25 mM | Standard Deviation 0.91 |
| ETOH Abuse | Anterior Cingulate Cortex - Glutamate | Scan 1 | 7.44 mM | Standard Deviation 0.65 |
| No ETOH Abuse | Anterior Cingulate Cortex - Glutamate | Scan 2 | 7.05 mM | Standard Deviation 2.02 |
| No ETOH Abuse | Anterior Cingulate Cortex - Glutamate | Scan 1 | 6.68 mM | Standard Deviation 1.86 |
| No ETOH Abuse | Anterior Cingulate Cortex - Glutamate | Difference | 0.26 mM | Standard Deviation 1.28 |
Primary
Anterior Cingulate Cortex - Myo-inositol
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)
Population: Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Anterior Cingulate Cortex - Myo-inositol | Scan 1 | 4.34 mM | Standard Deviation 0.53 |
| ETOH Abuse | Anterior Cingulate Cortex - Myo-inositol | Scan 2 | 4.00 mM | Standard Deviation 0.67 |
| ETOH Abuse | Anterior Cingulate Cortex - Myo-inositol | Difference | -0.17 mM | Standard Deviation 0.46 |
| No ETOH Abuse | Anterior Cingulate Cortex - Myo-inositol | Scan 1 | 4.00 mM | Standard Deviation 1.34 |
| No ETOH Abuse | Anterior Cingulate Cortex - Myo-inositol | Scan 2 | 4.35 mM | Standard Deviation 0.81 |
| No ETOH Abuse | Anterior Cingulate Cortex - Myo-inositol | Difference | 0.20 mM | Standard Deviation 0.46 |
Primary
Anterior Cingulate Cortex - N-acetylaspartate
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)
Population: Subjects entering baseline screening minus the two subjects with missing alcohol abuse history.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Anterior Cingulate Cortex - N-acetylaspartate | Scan 2 | 6.06 mM | Standard Deviation 0.59 |
| ETOH Abuse | Anterior Cingulate Cortex - N-acetylaspartate | Difference | -0.23 mM | Standard Deviation 0.35 |
| ETOH Abuse | Anterior Cingulate Cortex - N-acetylaspartate | Scan 1 | 6.40 mM | Standard Deviation 0.52 |
| No ETOH Abuse | Anterior Cingulate Cortex - N-acetylaspartate | Scan 2 | 6.14 mM | Standard Deviation 0.86 |
| No ETOH Abuse | Anterior Cingulate Cortex - N-acetylaspartate | Difference | 0.15 mM | Standard Deviation 0.53 |
| No ETOH Abuse | Anterior Cingulate Cortex - N-acetylaspartate | Scan 1 | 5.99 mM | Standard Deviation 1.11 |
Primary
Fractional Anisotropy Measured With Diffusion Tensor Imaging
Diffusion Tensor Imaging Frational Anisotropy (FA) Measures by Lifetime History of Alcohol Abuse/Dependence and Brain Hemisphere.
Time frame: Completion of two scans
Population: Subjects completing study (both scans).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Fractional Anisotropy Measured With Diffusion Tensor Imaging | Right hemisphere | 0.63 FA | Standard Deviation 0.03 |
| ETOH Abuse | Fractional Anisotropy Measured With Diffusion Tensor Imaging | Left hemisphere | 0.59 FA | Standard Deviation 0.04 |
| No ETOH Abuse | Fractional Anisotropy Measured With Diffusion Tensor Imaging | Right hemisphere | 0.61 FA | Standard Deviation 0.05 |
| No ETOH Abuse | Fractional Anisotropy Measured With Diffusion Tensor Imaging | Left hemisphere | 0.57 FA | Standard Deviation 0.04 |
Primary
Left Dorsal Lateral Prefrontal Cortex - Choline
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Choline | Scan 1 | 1.53 mM | Standard Deviation 0.36 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Choline | Scan 2 | 1.57 mM | Standard Deviation 0.2 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Choline | Difference | 0.05 mM | Standard Deviation 0.24 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Choline | Scan 1 | 1.53 mM | Standard Deviation 0.23 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Choline | Scan 2 | 1.65 mM | Standard Deviation 0.21 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Choline | Difference | 0.10 mM | Standard Deviation 0.23 |
Primary
Left Dorsal Lateral Prefrontal Cortex - Creatinine
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 1 | 5.38 mM | Standard Deviation 0.84 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 2 | 5.43 mM | Standard Deviation 1.13 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Creatinine | Difference | 0.15 mM | Standard Deviation 0.82 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 1 | 5.78 mM | Standard Deviation 0.64 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 2 | 5.86 mM | Standard Deviation 0.53 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Creatinine | Difference | 0.11 mM | Standard Deviation 0.55 |
Primary
Left Dorsal Lateral Prefrontal Cortex - Glutamate
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 2 | 6.86 mM | Standard Deviation 1.03 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Glutamate | Difference | -0.50 mM | Standard Deviation 1.36 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 1 | 7.45 mM | Standard Deviation 1.21 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 1 | 6.98 mM | Standard Deviation 1.07 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 2 | 6.92 mM | Standard Deviation 0.55 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Glutamate | Difference | 0.03 mM | Standard Deviation 1.32 |
Primary
Left Dorsal Lateral Prefrontal Cortex - Myo-inositol
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 1 | 3.69 mM | Standard Deviation 0.79 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Myo-inositol | Difference | -0.08 mM | Standard Deviation 0.97 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 2 | 3.34 mM | Standard Deviation 0.64 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 1 | 3.61 mM | Standard Deviation 0.69 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 2 | 4.08 mM | Standard Deviation 0.91 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - Myo-inositol | Difference | 0.51 mM | Standard Deviation 0.72 |
Primary
Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 1 | 7.22 mM | Standard Deviation 0.99 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 2 | 7.44 mM | Standard Deviation 1.25 |
| ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Difference | 0.25 mM | Standard Deviation 0.77 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 1 | 7.50 mM | Standard Deviation 0.87 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Difference | 0.16 mM | Standard Deviation 0.91 |
| No ETOH Abuse | Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 2 | 8.04 mM | Standard Deviation 1.68 |
Primary
Right Dorsal Lateral Prefrontal Cortex - Choline
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Choline | Scan 1 | 1.36 mM | Standard Deviation 0.29 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Choline | Scan 2 | 1.32 mM | Standard Deviation 0.17 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Choline | Difference | 0.06 mM | Standard Deviation 0.16 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Choline | Scan 1 | 1.30 mM | Standard Deviation 0.29 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Choline | Difference | 0.40 mM | Standard Deviation 1.2 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Choline | Scan 2 | 1.71 mM | Standard Deviation 1.11 |
Primary
Right Dorsal Lateral Prefrontal Cortex - Creatinine
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 1 | 5.51 mM | Standard Deviation 0.61 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 2 | 5.52 mM | Standard Deviation 0.51 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Creatinine | Difference | 0.27 mM | Standard Deviation 0.64 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 1 | 5.48 mM | Standard Deviation 0.92 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Creatinine | Scan 2 | 5.54 mM | Standard Deviation 0.7 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Creatinine | Difference | 0.11 mM | Standard Deviation 0.76 |
Primary
Right Dorsal Lateral Prefrontal Cortex - Glutamate
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 1 | 6.89 mM | Standard Deviation 1.1 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 2 | 6.63 mM | Standard Deviation 1.03 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Glutamate | Difference | -0.44 mM | Standard Deviation 1.52 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 1 | 7.51 mM | Standard Deviation 2 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Glutamate | Scan 2 | 7.15 mM | Standard Deviation 0.92 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Glutamate | Difference | -0.69 mM | Standard Deviation 1.9 |
Primary
Right Dorsal Lateral Prefrontal Cortex - Myo-inositol
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 1 | 3.73 mM | Standard Deviation 0.72 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 2 | 3.41 mM | Standard Deviation 0.43 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Myo-inositol | Difference | -0.17 mM | Standard Deviation 0.66 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 1 | 3.71 mM | Standard Deviation 0.43 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Myo-inositol | Scan 2 | 3.44 mM | Standard Deviation 0.68 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - Myo-inositol | Difference | -0.24 mM | Standard Deviation 0.76 |
Primary
Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate
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)
Population: Usable scan data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 1 | 7.43 mM | Standard Deviation 0.78 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Difference | 0.35 mM | Standard Deviation 0.78 |
| ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 2 | 7.65 mM | Standard Deviation 0.54 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 1 | 7.65 mM | Standard Deviation 1.03 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Scan 2 | 8.15 mM | Standard Deviation 1.24 |
| No ETOH Abuse | Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate | Difference | 0.42 mM | Standard Deviation 0.96 |
Secondary
BPRS - Symptoms of Psychosis Change in Scores
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)
Population: Subjects completing the BPRS rating at Baseline and End of Study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Hallucinations Change | -0.0909 units on a scale | Standard Deviation 1.7581 |
| ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Unusual Thought Content Change | -0.0909 units on a scale | Standard Deviation 1.1362 |
| ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Suspiciousness Change | -0.636 units on a scale | Standard Deviation 2.111 |
| ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Conceptual Disorganization Change | -0.182 units on a scale | Standard Deviation 0.603 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Suspiciousness Change | -0.532 units on a scale | Standard Deviation 1.209 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Hallucinations Change | -0.6250 units on a scale | Standard Deviation 1.3102 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Unusual Thought Content Change | -0.1250 units on a scale | Standard Deviation 0.7188 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Change in Scores | Conceptual Disorganization Change | 0.0 units on a scale | Standard Deviation 0.73 |
Secondary
BPRS - Symptoms of Psychosis Total Score
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)
Population: Subjects completing BPRS rating at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | BPRS - Symptoms of Psychosis Total Score | Baseline | 8.88 units on a scale | Standard Deviation 3.77 |
| ETOH Abuse | BPRS - Symptoms of Psychosis Total Score | End of study | 8.82 units on a scale | Standard Deviation 4.14 |
| ETOH Abuse | BPRS - Symptoms of Psychosis Total Score | Change | -1.00 units on a scale | Standard Deviation 3.95 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Total Score | Baseline | 9.47 units on a scale | Standard Deviation 4.45 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Total Score | End of study | 8.38 units on a scale | Standard Deviation 4.16 |
| No ETOH Abuse | BPRS - Symptoms of Psychosis Total Score | Change | -1.31 units on a scale | Standard Deviation 2.33 |
Secondary
Cognitive Impairment
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)
Population: Subjects who completed cognitive testing at both study time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | Cognitive Impairment | Change in DigitSymbol Scaled Score | -0.20 units on a scale | Standard Deviation 1.03 |
| ETOH Abuse | Cognitive Impairment | Change in NBack 1-Back Total Hits | 0.60 units on a scale | Standard Deviation 3.2 |
| ETOH Abuse | Cognitive Impairment | Change in CVLT Total Recall | -0.600 units on a scale | Standard Deviation 1.955 |
| ETOH Abuse | Cognitive Impairment | Change in NBack 2-Back Total Hits | 1.70 units on a scale | Standard Deviation 2.41 |
| ETOH Abuse | Cognitive Impairment | Change in NBack 0-Back Total Hits | 0.000 units on a scale | Standard Deviation 1.886 |
| No ETOH Abuse | Cognitive Impairment | Change in NBack 2-Back Total Hits | 1.71 units on a scale | Standard Deviation 3.27 |
| No ETOH Abuse | Cognitive Impairment | Change in NBack 0-Back Total Hits | 0.214 units on a scale | Standard Deviation 1.188 |
| No ETOH Abuse | Cognitive Impairment | Change in CVLT Total Recall | -0.143 units on a scale | Standard Deviation 1.956 |
| No ETOH Abuse | Cognitive Impairment | Change in NBack 1-Back Total Hits | 1.14 units on a scale | Standard Deviation 3.42 |
| No ETOH Abuse | Cognitive Impairment | Change in DigitSymbol Scaled Score | 0.00 units on a scale | Standard Deviation 1.3 |
Secondary
SANS - Negative Symptoms of Schizophrenia Total Score
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)
Population: Subjects completing the SANS assessment at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ETOH Abuse | SANS - Negative Symptoms of Schizophrenia Total Score | Baseline | 23.50 units on a scale | Standard Deviation 10.73 |
| ETOH Abuse | SANS - Negative Symptoms of Schizophrenia Total Score | End of study | 24.18 units on a scale | Standard Deviation 12.09 |
| ETOH Abuse | SANS - Negative Symptoms of Schizophrenia Total Score | Change | 2.091 units on a scale | Standard Deviation 8.384 |
| No ETOH Abuse | SANS - Negative Symptoms of Schizophrenia Total Score | Baseline | 26.12 units on a scale | Standard Deviation 9.14 |
| No ETOH Abuse | SANS - Negative Symptoms of Schizophrenia Total Score | End of study | 26.38 units on a scale | Standard Deviation 9.49 |
| No ETOH Abuse | SANS - Negative Symptoms of Schizophrenia Total Score | Change | -0.375 units on a scale | Standard Deviation 6.407 |