Trial of D-Cycloserine in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: D-cycloserine; Placebo
Intervention description: 50 mg/daily by mouth; 50 mg/day of placebo by mouth
Intervention MeSH terms: Cycloserine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Adult; Cognition; Cycloserine; Dopamine; Female; Glutamic Acid; Human; Male; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Serotonin; Quality of Life; Cycloserine -- *therapeutic use; Dopamine -- blood; Dopamine -- cerebrospinal fluid; Glutamic Acid -- blood; Glutamic Acid -- cerebrospinal fluid; Serotonin -- blood; Serotonin -- cerebrospinal fluid

Summary:

      To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment
      on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic,
      dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if
      negative symptoms and cognitive function improve over time, if these improvements
      meaningfully impact quality of life factors, if they correlate with markers of neuronal
      function, and if subpopulations can be identified according to response.

      Dysfunction of glutamatergic neuronal systems has recently been implicated in the
      pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the
      NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and
      cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter
      forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of
      typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic
      treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA
      receptor, will reduce symptoms in schizophrenia.

      Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with
      antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month,
      fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment
      of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive
      to prefrontal cortical function, is administered. Blood is obtained at several time points
      and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA,
      and 5HIAA.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Schizophrenia as per DSM IV criteria

          -  Have been treated for at least 6 months with any conventional neuroleptic

          -  Have prominent negative symptoms as defined by a total score of 40 or greater on the
             scale for the assessment of negative symptoms (SANS)

        Exclusion Criteria:

          -  Active alcohol or drug abuse

          -  Unstable Medical Illness, seizure disorder, or other serious neurological disorder

          -  Pregnant or Nursing

          -  Unable to complete a cognitive battery