Phase 2 Trial of a Nicotinic Agonist in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      The study hypothesis is that 3-2,4 dimethoxybenzylidene anabaseine (DMXB-A), an orally
      administered nicotinic cholinergic agonist, will improve attention and other
      neuropsychological dysfunctions in schizophrenia, leading to improved psychosocial outcome.
    

Detailed description: 
      The objective of the trial is to determine if dosing 3-(2,4 dimethoxybenzylidene anabaseine)
      twice daily for 4 weeks will improve cognition and be safe. Secondary goals are to determine
      if these neurocognitive effects also have effects on neurobiological paradigms previously
      shown to be responsive to nicotinic receptor stimulation: suppression of P50 auditory evoked
      response, saccadic intrusions during smooth pursuit eye movements, and hemodynamic activity
      in the hippocampus during smooth pursuit eye movements as measured by functional magnetic
      resonance imaging. The purpose of these neurobiological measures is to assess whether the
      response to 3-(2,4 dimethoxybenzylidene anabaseine) is consistent with activation of
      nicotinic receptors. In addition, the investigators will assess clinical response using a
      battery of clinical assessment scales and assessments of daily living functions. The purpose
      of these assessments is to address the FDA requirement of a clinical effect beyond change in
      laboratory neuropsychological performance. This study and the subsequent two studies will
      also include assessments of the safety of 3-(2,4 dimethoxybenzylidene anabaseine) and related
      compounds.

      The purpose of the trial is to lay the groundwork for Phase III investigation. If this trial
      finds that 3-(2,4 dimethoxybenzylidene anabaseine) has effects at a safe dose, without
      tachyphylaxis, then the investigators intend to proceed to a Phase III trial, where the
      clinical importance of this effect can be measured.

      The trial will be a double blind trial with placebo control. The order of doses and placebo
      will be randomized.

      The Phase 1 study was completed in January, 2005, with 12 non-smoking schizophrenics
      subjects. The subjects were concurrently treated with neuroleptics throughout the study. They
      received 3 treatments, each for 1 day, in a double-blind crossover design. The treatments
      were 3-(2,4 dimethoxybenzylidene anabaseine) (150 mg + 75 mg 2 hours later), 3-(2,4
      dimethoxybenzylidene anabaseine)(75 mg + 37.5 mg 2 hours later), and placebo. A significant
      effect on neurocognition, as measured by the Repeatable Battery for Assessment of
      Neuropsychological Status, and on sensory gating, as measured by P50 auditory evoked
      potentials was observed. Subjects reported no significant symptoms. One subject's white blood
      cell count decreased from just above normal limits on placebo to just below normal levels on
      3-(2,4 dimethoxybenzylidene anabaseine)(150 + 75 mg 2 hours later). He did not receive
      further exposure to drug and his white blood cell count returned to normal at the next
      testing, 2 days later.
    

Intervention name(s): Placebo; 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg; 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Placebo by mouth twice a day for 4 weeks; 3-(2,4 dimethoxybenzylidene) 150 mg by mouth twice a day for 4 weeks; 3-(2,4 dimethoxybenzylidene) 75 mg by mouth twice a day for 4 weeks
Other intervention name(s): inactive substance; GTS-21; GTS-21
Intervention MeSH terms: 3-(2,4-dimethoxybenzylidene)anabaseine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia