Biomarker Study of Acamprosate in Schizophrenia

NCT00688324 | Completed Phase 4 Results DMC

• 2 other identifiers: HP-00043248R03AA019571
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

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.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

schizophrenia; schizoaffective disorder; glutamate; NMDA receptor; magnetic resonance spectroscopy; acamprosate

Outcome Measures

Primary Outcomes (16)

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• 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".

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

• Fractional Anisotropy Measured With Diffusion Tensor Imaging

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

  Completion of two scans

Secondary Outcomes (4)

• BPRS - Symptoms of Psychosis Change in Scores

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

• BPRS - Symptoms of Psychosis Total Score

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

• SANS - Negative Symptoms of Schizophrenia Total Score

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

• Cognitive Impairment

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

Study Arms (1)

Single Arm

EXPERIMENTAL

All subjects will have baseline measures, receive acamprosate for 2 weeks, then have measures repeated.

Drug: Acamprosate

Interventions

Acamprosate DRUG

Acamprosate 333mg, ii tablets PO tid x 2 weeks

Also known as: Campral

Single Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (4)

VA Maryland Health Care System

Baltimore, Maryland, 21201, United States

Location

Keypoint Community Mental Health Centers- Dundalk

Baltimore, Maryland, 21222, United States

Location

Keypoint Community Mental Health Centers- Catonsville

Baltimore, Maryland, 21228, United States

Location

Maryland Psychiatric Research Center

Baltimore, Maryland, 21228, United States

Location

Related Links

• Maryland Psychiatric Research Center

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Acamprosate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Robert W. Buchanan, M.D.
• Organization: Maryland Psychiatric Research Center

rwbuchanan@som.umaryland.edu

410-402-7876

Study Officials

• Bernard A Fischer, M.D.

  Food and Drug Administration (FDA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Maryland Psychiatric Research Center, Outpatient Research Program

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: June 2, 2008
• Study Start: June 1, 2008
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: September 25, 2019
• Results First Posted: January 23, 2018

Record last verified: 2019-09

Locations

US (4)