Galantamine for Cognition in People With Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is a double-blind, placebo-controlled trial of the nicotinic receptor agonist,
      galantamine, for the improvement of memory and attention in people with schizophrenia and
      schizoaffective disorder. Twenty subjects on a stable dose of antipsychotic medications
      receive galantamine or identical placebo tablets for 8 weeks. Adverse events are screened for
      every week. Tests of memory, attention, and reward responsivity are performed at baseline and
      afer 8 weeks on medication. Clinical scales rating psychiatric symptoms are performed at the
      beginning, middle, and end of the trial.
    

Detailed description: 
      Background:

      Galantamine is a novel acetylcholinesterase inhibitor that is also a positive allosteric
      modulator of nicotinic acetylcholine receptors. Galantamine has been shown to increase
      conductivity of nicotinic receptors through a binding site that is discreet from the
      acetylcholine receptor. There is minimal risk of overstimulation with positive allosteric
      modulators as they do not produce receptor depolarization but potentiate submaximal
      acetylcholine induced depolarization. Our hypothesis is that allosteric modulation of
      nicotinic acetylcholine receptors is a potentially important treatment strategy in
      schizophrenia. We propose a trial of galantamine augmentation of antipsychotic medication in
      the treatment of schizophrenia to test the following hypotheses.

      Hypotheses:

        1. Galantamine augmentation of antipsychotic treatment will be associated with improvement
           from baseline in performance on the cognitive battery: Stroop, Cornblatt CPT-IP, CDR
           Battery, letter number span, Grooved peg board, Tower of London, and Signal Detection
           Task.

        2. Galantamine augmentation of high potency antipsychotic treatment will be well tolerated
           and associated with improvement from baseline in negative symptoms (SANS), depressive
           symptoms (CDSS) and impulsivity (PANSS aggression item).

      Study Design:

      Twenty adult subjects, aged 18-60, will be randomized, according to a double blind, parallel
      group design, to receive galantamine or identical placebo for 8 weeks. Subjects will begin
      with a dose of up to 8 mg twice per day for the first four weeks, then up to 16 mg twice per
      day for the next four weeks. Visits will be weekly to monitor medication compliance and
      medication side effects. Prior to beginning treatment, subjects will undergo a 1.5 hour
      training session to familiarize themselves with the CDR battery portion of the cognitive
      battery. Subjects will then be evaluated for symptoms of psychosis, depression, anxiety,
      smoking behavior and medication side effects with standard clinical rating scales that
      include the Schedule for Assessment of Negative Symptoms (SANS), Positive and Negative
      Symptom Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Calgary Depression Scale for
      Schizophrenia (CDSS), Abnormal Involuntary Movement Scale (AIMS), Simpson Angus Scale and
      Barnes Akathisia Scale, Fagerstrom Test of Nicotine Dependence, carbon monoxide measurement
      and smoking self report. Subjects who meet criteria for current depression or who have
      suicidal ideation will be excluded. Clinical rating scales will be performed at baseline and
      monthly. Tests of visual and spatial working memory, attention, motor skills, inhibition, and
      motivation will be performed at baseline and at 8 weeks. The cognitive battery will include
      tests of response inhibition (the 3-card Stroop), attention (Cornblatt continuous performance
      test identical pairs (CPT-IP) and CDR Battery), verbal memory (CDR Battery), working memory
      (letter-number span), non-verbal memory (CDR Battery), psychomotor ability (grooved peg board
      task), executive functioning (Tower of London), and motivation for reward (signal detection
      task). Blood will be drawn for antipsychotic levels, galantamine levels, and measurement of
      nicotinic receptor number at baseline and 8 weeks. Adverse events will be documented at each
      visit using an Adverse Events Tracking log. At baseline and week 8 carbon monoxide (CO)
      measurements will be used with self report to verify number of cigarettes smoked per day.
    

Intervention name(s): galantamine
Intervention type(s): Drug
Intervention MeSH terms: Galantamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: schizophrenia; cognitive function; cholinergic medication; nicotinic receptor agonist