Trial of DMXB-A in Schizophrenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00100165
First received: December 23, 2004
Last updated: September 10, 2014
Last verified: September 2014

December 23, 2004
September 10, 2014
January 2005
December 2014   (final data collection date for primary outcome measure)
Neurocognitive performance [ Time Frame: 1 month ] [ Designated as safety issue: No ]
MATRICS
Neurocognitive improvement on the Matrics Battery
Complete list of historical versions of study NCT00100165 on ClinicalTrials.gov Archive Site
Psychosocial function [ Time Frame: 1 month ] [ Designated as safety issue: No ]
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, 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 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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Schizophrenia
  • Drug: 3-2,4 dimethoxybenzylidene 75 or 150 mg bid
    3-2,4 dimethoxybenzylidene 75 or 150 mg bid
  • Drug: Placebo
    Placebo
  • Experimental: Arm 1
    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 ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
December 2014
December 2014   (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
Both
18 Years to 65 Years
No
Contact: Robert Freedman, MD (303) 315-8403 Robert.Freedman@ucdenver.edu
United States
 
NCT00100165
57710-2, VISN 19 MIRECC
Yes
Department of Veterans Affairs
Department of Veterans Affairs
Not Provided
Principal Investigator: Robert Freedman, MD VA Eastern Colorado Health Care System, Denver
Department of Veterans Affairs
September 2014

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