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.

Condition	Treatment or Intervention	Phase
Schizophrenia	Drug: 3-2,4 dimethoxybenzylidene 75 or 150 mg bid	Phase II

Further Study Details: 

Primary Outcomes: Neurocognitive improvement on the Matrics Battery
Secondary Outcomes: Psychosocial function
Expected Total Enrollment:  24

The objective of the trial is to determine if dosing DMXB-A 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 fMRI. The purpose of these neurobiological measures is to assess whether the response to DMXB-A is consistent with activation of nicotinic receptors. In addition, we 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 DMXB-A and related compounds. The purpose of the trial is to lay the groundwork for Phase III investigation. If this trial finds that DMXB-A has effects at a safe dose, without tachyphylaxis, then we 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 DMXB-A (150 mg + 75 mg 2 hours later), DMXB-A (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 eovked 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 DMXBA (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.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Schizophrenia
• Currently treated with neuroleptic drugs

Exclusion Criteria:

• Treatment with clozapine;
• Head injury or neurological condition;
• Cardiovascular disease;
• Substance abuse or dependence, including nicotine

Christopher Cason, BS      303-807-7382    Christopher.Cason@UCHSC.edu
Robert Freedman, MD      303-315-8403    Robert.Freedman@UCHSC.edu

Colorado
      Denver VA Medical Center, Denver,  Colorado,  80222,  United States; Recruiting

Study chairs or principal investigators

Robert Freedman, MD,  Principal Investigator,  Department of Veterans Affairs   

Study ID Numbers:  57710-2; VISN 19 MIRECC
Record last reviewed:  January 2005
Last Updated:  January 24, 2005
Record first received:  December 23, 2004
ClinicalTrials.gov Identifier:  NCT00100165
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08