Biomarker Study of Acamprosate in Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Acamprosate
Intervention type(s): Drug
Intervention description(s): Acamprosate 333mg, ii tablets PO tid x 2 weeks
Other intervention name(s): Campral
Intervention MeSH terms: Acamprosate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; schizoaffective disorder; glutamate; NMDA receptor; magnetic resonance spectroscopy; acamprosate