Phase 4 Completed N=36 Treatment

Biomarker Study of Acamprosate in Schizophrenia

Schizophrenia · schizoaffective disorder

Source: ClinicalTrials.gov NCT00688324 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jan 2018

Primary outcomePrimary: Anterior Cingulate Cortex - Choline — 1.64; 1.54; 1.46; 1.58 mM

◆ Published Evidence

No publication linked

No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Anterior Cingulate Cortex - Choline	1.64; 1.54; 1.46; 1.58; -0.10; 0.04	—
PRIMARY Anterior Cingulate Cortex - Creatinine	5.46; 5.12; 5.09; 5.16; -0.14; 0.07	—
PRIMARY Anterior Cingulate Cortex - Glutamate	7.44; 6.68; 7.06; 7.05; -0.25; 0.26	—
PRIMARY Anterior Cingulate Cortex - N-acetylaspartate	6.40; 5.99; 6.06; 6.14; -0.23; 0.15	—
PRIMARY Anterior Cingulate Cortex - Myo-inositol	4.34; 4.00; 4.00; 4.35; -0.17; 0.20	—
PRIMARY Right Dorsal Lateral Prefrontal Cortex - Choline	1.36; 1.30; 1.32; 1.71; 0.06; 0.40	—
PRIMARY Right Dorsal Lateral Prefrontal Cortex - Creatinine	5.51; 5.48; 5.52; 5.54; 0.27; 0.11	—
PRIMARY Right Dorsal Lateral Prefrontal Cortex - Glutamate	6.89; 7.51; 6.63; 7.15; -0.44; -0.69	—
PRIMARY Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate	7.43; 7.65; 7.65; 8.15; 0.35; 0.42	—
PRIMARY Right Dorsal Lateral Prefrontal Cortex - Myo-inositol	3.73; 3.71; 3.41; 3.44; -0.17; -0.24	—
PRIMARY Left Dorsal Lateral Prefrontal Cortex - Choline	1.53; 1.53; 1.57; 1.65; 0.05; 0.10	—
PRIMARY Left Dorsal Lateral Prefrontal Cortex - Creatinine	5.38; 5.78; 5.43; 5.86; 0.15; 0.11	—
PRIMARY Left Dorsal Lateral Prefrontal Cortex - Glutamate	7.45; 6.98; 6.86; 6.92; -0.50; 0.03	—
PRIMARY Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate	7.22; 7.50; 7.44; 8.04; 0.25; 0.16	—
PRIMARY Left Dorsal Lateral Prefrontal Cortex - Myo-inositol	3.69; 3.61; 3.34; 4.08; -0.08; 0.51	—
PRIMARY Fractional Anisotropy Measured With Diffusion Tensor Imaging	0.63; 0.61; 0.59; 0.57	—
SECONDARY BPRS - Symptoms of Psychosis Change in Scores	-0.182; 0.0; -0.636; -0.532; -0.0909; -0.6250	—
SECONDARY BPRS - Symptoms of Psychosis Total Score	8.88; 9.47; 8.82; 8.38; -1.00; -1.31	—
SECONDARY SANS - Negative Symptoms of Schizophrenia Total Score	23.50; 26.12; 24.18; 26.38; 2.091; -0.375	—
SECONDARY Cognitive Impairment	0.000; 0.214; 0.60; 1.14; 1.70; 1.71	—

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00688324). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.