Trial of DMXB-A in Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00100165
Recruitment Status : Unknown
Verified December 2015 by VA Office of Research and Development.
Recruitment status was:  Recruiting
First Posted : December 24, 2004
Last Update Posted : December 7, 2015
Information provided by (Responsible Party):
VA Office of Research and Development

December 23, 2004
December 24, 2004
December 7, 2015
January 2005
December 2015   (Final data collection date for primary outcome measure)
Neurocognitive performance [ Time Frame: 1 month ]
Neurocognitive improvement on the Matrics Battery
Complete list of historical versions of study NCT00100165 on Archive Site
Psychosocial function [ Time Frame: 1 month ]
Psychosocial function
Not Provided
Not Provided
Trial of DMXB-A in Schizophrenia
Phase 2 Trial of 3-2,4 Dimethoxybenzylidene Anabaseine in Schizophrenia
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.

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.

Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Drug: 3-2,4 dimethoxybenzylidene 75 or 150 mg bid
    3-2,4 dimethoxybenzylidene 75 or 150 mg bid
  • Drug: Placebo
  • Experimental: Arm 1: Experimental Drug
    Experimental Drug
    Intervention: Drug: 3-2,4 dimethoxybenzylidene 75 or 150 mg bid
  • Placebo Comparator: Arm 2: Placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Unknown status
December 2016
December 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
United States
VISN 19 MIRECC ( Other Grant/Funding Number: VA )
Not Provided
Not Provided
VA Office of Research and Development
VA Office of Research and Development
Not Provided
Principal Investigator: Robert Freedman, MD VA Eastern Colorado Health Care System, Denver, CO
VA Office of Research and Development
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP