The Effect of N-Acetyl Cysteine on Cortical Erosion in Early Stage Schizophrenia
Condition: Schizophrenia; Psychotic Disorder NOS; Schizoaffective Disorder; Schizophreniform
MeSH terms: Schizophrenia; Mental Disorders; Psychotic Disorders
Intervention: N-Acetyl Cysteine; sugar pill
Intervention description: NAC and matched placebo will be supplied in unmarked capsules. Each NAC capsule will contain 480 mg of NAC. Dosing will begin at 480 mg/d and titrated up by 480 mg/d each week until a maximum dose of 2880 mg/d (BID) is reached. This approximate dose was effective and well tolerated in a recent study of treatment refractory obsessive-compulsive disorder by Krystal and colleagues at Yale (16). In addition, a double-blind placebo controlled trial recently completed at IUSM Riley Hospital in children (age 4 to 12 years) with autism spectrum disorders used doses ranging from 900 mg/day to 4200 mg/day and reported no serious adverse events and found the agent well tolerated (15). Dose adjustments downward to 1920 mg/d will be permitted if tolerability issues are encountered at the maximum dose; matched placebo will be supplied in unmarked capsules. Dosing regimen will be the same as in the N-Acetyl Cysteine arm.
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 60.0
Sex: All
Minimum age: 16 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study is to determine if NAC, added to existing antipsychotic
      treatment, is superior to placebo for cortical erosion in patients with early stage
      psychosis. The primary hypothesis is that there will be significantly less cortical erosion
      as measured by cortical thickness, cortical volume and cortical white matter density
      (assessed by DTI) in patients treated for 12 months with NAC as compared to those treated
      with placebo. The secondary objectives of this study are to determine if 12 months of NAC
      add-on treatment is superior to placebo for fMRI determined working memory and semantic
      memory tasks, cortical MR spectroscopy measures (glutathione, N-acetylaspartate, and
      glutamine/glutamate levels), electrophysiologically determined attention measures (e.g.,
      mismatch negativity, P300), symptoms, functional measures and cognitive functioning.
    

Eligibility criteria:

        SUBJECTS DIAGNOSED WITH A PSYCHOTIC DISORDER

        Inclusion Criteria:

          -  Patients with a DSM-IV diagnosis of schizophrenia, schizophreniform, schizoaffective,
             psychosis disorder NOS

          -  Age range 16-35 years

          -  Male or female

          -  Within 2 years of the first onset of psychotic symptoms that resulted in
             work/school/social dysfunction and/or treatment (PI will review potential subjects who
             have been experiencing symptoms >2 years but <5 years and will allow to enter the
             trial on a case-by-case basis)

          -  Ability to provide informed consent and/or assent (all subjects)

          -  For subjects 16 and 17 years of age, parental/guardian consent

        Exclusion Criteria:

          -  Unstable medical conditions

          -  Active seizure disorder

          -  Pregnant or lactating women

          -  Females unwilling to utilize birth control

          -  Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS
             unit, or ventriculoperitoneal shunt (because of MR studies).

          -  Known IQ less than 70

          -  DSM-IV-TR diagnosis of substance dependence (with the exception of nicotine or
             caffeine dependence)

          -  Psychotic symptoms secondary to substance use

          -  Considered a high risk for suicidal acts - active suicidal ideation with intent to act
             as determined by clinical interview

        HEALTHY CONTROL SUBJECTS

        The comparison subjects will consist of 40 healthy normal volunteers recruited from the
        community who will be age and gender matched to subjects diagnosed with a psychotic
        disorder entering the NAC treatment study

        Inclusion Criteria:

          1. Age range of 18-30 (inclusive) and able to give voluntary informed consent (Note:
             Subjects diagnosed with a psychotic disorder under the age of 18 will be age matched
             to control subjects aged 18).

          2. Male or Female

        Exclusion Criteria:

          1. Current severe mental disorder (Schizophrenia, schizophreniform disorder, other
             psychotic disorders, bipolar disorder, major depressive disorder)

          2. Known/documented IQ < 70

          3. Pregnant or lactating women

          4. Acute, serious, or unstable medical condition

          5. Metallic implants or other contraindication to MRI (including but not limited to:
             Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS
             unit, or ventriculoperitoneal shunt)

          6. First degree relative with a psychotic disorder (i.e. schizophrenia, schizophreniform,
             schizoaffective, psychosis disorder NOS, substance induced psychosis, major depression
             with psychotic features, or bipolar disorder with psychotic features).

          7. Current DSM-IV-TR diagnosis of substance abuse or dependence (with the exception of
             nicotine or caffeine) as diagnosed within the 6 months prior to screening visit

          8. Known history of seizure disorder, head trauma, stroke, traumatic brain injury,
             significant loss of consciousness