Trial of DMXB-A in Schizophrenia
|Schizophrenia||Drug: 3-2,4 dimethoxybenzylidene 75 or 150 mg bid Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase 2 Trial of 3-2,4 Dimethoxybenzylidene Anabaseine in Schizophrenia|
- Neurocognitive performance [ Time Frame: 1 month ]MATRICS
- Psychosocial function [ Time Frame: 1 month ]
|Study Start Date:||January 2005|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm 1: Experimental Drug
Drug: 3-2,4 dimethoxybenzylidene 75 or 150 mg bid
3-2,4 dimethoxybenzylidene 75 or 150 mg bid
Placebo Comparator: Arm 2: Placebo
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, 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 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 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 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 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00100165
|Contact: Robert Freedman, MD||(303) 315-0626||Robert.Freedman@ucdenver.edu|
|United States, Colorado|
|VA Eastern Colorado Health Care System, Denver, CO||Recruiting|
|Denver, Colorado, United States, 80220|
|Contact: Robert Freedman, MD 303-315-0626 Robert.Freedman@ucdenver.edu|
|Principal Investigator: Robert Freedman, MD|
|Principal Investigator:||Robert Freedman, MD||VA Eastern Colorado Health Care System, Denver, CO|