Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia; Cognitive Dysfunction
Intervention: Oxytocin; Galantamine; Placebo-Oxytocin; Placebo-Galantamine
Intervention description: Oxytocin: 24 IU in the morning and 24 IU in the evening given by nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration; Galantamine: 4 mg twice a day for 1 week, then 8 mg twice a day for 1 week, then 12 mg twice a day for 4 weeks; Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration; Placebo tablets twice a day for 6 weeks
Intervention MeSH terms: Galantamine; Oxytocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Schizophrenia, oxytocin, galantamine

Summary:

      The project is designed to address the following two primary aims:

        1. To determine whether adjunctive oxytocin is superior to placebo for the treatment of
           persistent negative symptoms, as measured by the SANS total score, in people with
           schizophrenia.

        2. To determine whether adjunctive Galantamine is superior to placebo for the treatment of
           cognitive impairments, as measured by improvement on a composite neurocognitive score in
           people with schizophrenia.

      The investigators will also address the following secondary aims:

        1. To determine whether people with schizophrenia treated with adjunctive oxytocin,
           compared to placebo, will show greater improvement on markers of negative symptom
           liability including: social affiliation, facial affect recognition, olfactory
           discrimination, initiation of smooth pursuit and latency of internally-driven saccades.

        2. To determine whether people with schizophrenia treated with adjunctive Galantamine,
           compared to placebo, will show greater improvement on markers of cognitive impairment
           liability including: predictive pursuit, P50 sensory gating and visual-spatial working
           memory.

      The investigators will address the following exploratory aims:

        1. To determine whether changes in markers of negative symptom liability are correlated
           with changes in SANS total score.

        2. To determine whether changes in markers of cognitive impairment liability are correlated
           with changes in the composite neurocognitive score.

        3. To determine the response to oxytocin of all cognition domains assessed by the MATRICS
           battery, and to determine the response to Galantamine of all cognition domains assessed
           by the MATRICS, which are not included in the primary neurocognitive outcome score.

        4. To determine whether there is a differential response of oxytocin and Galantamine on the
           SANS total score, composite neurocognitive score, and with the phenotypic measures of
           negative symptom and cognitive impairment liability.

        5. To determine whether oxytocin and Galantamine are associated with:

             -  adverse effects on positive or depressive symptoms;

             -  adverse effects on motor symptoms;

             -  adverse effects on laboratory and EKG measures;

             -  increased occurrence of side effects;

             -  social interest that is independent of sexual desire.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any race

          -  Subjects will meet DSM-IV criteria for schizophrenia or schizoaffective disorder

          -  Judged clinically stable and will not exceed threshold levels of positive, depressive,
             and/or extrapyramidal symptoms

          -  The minimum level of negative symptoms will be defined as follows:

               -  Scale for the Assessment of Negative Symptoms (SANS) total score (minus the
                  global items, and inappropriate affect, poverty of content of speech and
                  attentional items) 20 or greater; OR

               -  SANS alogia global item score 3 or greater

          -  The maximum level of psychotic, depressive, and extrapyramidal symptoms at the
             beginning and end of leading in:

               -  Brief Psychiatric Rating Scale (BPRS) psychotic factor score (4-items) less or
                  equal to 16

               -  BPRS Anxiety/Depression factor score (4-items) less than or equal to 14

               -  Simpson-Angus-Scale (SAS) total score (13-items) less than or equal to 10

          -  Subjects will be required to be on the same antipsychotic(s) for two months and on the
             same dose for the last month

        Exclusion Criteria:

          -  Participants with an organic brain disorder; mental retardation; or a medical
             condition, whose pathology or treatment could alter the presentation or treatment of
             schizophrenia or significantly increase the risk associated with the proposed
             treatment protocol

          -  Participants with intermittent alcohol or substance use will not be excluded unless
             they have met DSM-IV criteria for alcohol or substance abuse (other than nicotine)
             within the last month.

          -  Participants may be treated with one or more antipsychotics, except chlorpromazine,
             thioridazine, or mesoridazine. These latter antipsychotics are excluded because of the
             concern that their anticholinergic properties may interfere with the accurate
             assessment of galantamine efficacy.

          -  Participants may not be treated with anticholinergic medications or have clinically
             significant extrapyramidal symptoms. Additionally, subjects treated with
             glycopyrrolate will be accepted.

          -  Female participants may not be pregnant

          -  Female subjects may not be taking olanzapine at doses higher than 30 mg . Male
             subjects may not be taking olanzapine at doses higher than 40 mg.