Trial of DMXB-A in Schizophrenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 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: April 23, 2014
Last verified: April 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2 Trial of 3-2,4 Dimethoxybenzylidene Anabaseine in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Neurocognitive performance [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    MATRICS


Secondary Outcome Measures:
  • Psychosocial function [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: January 2005
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Placebo
Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00100165

Contacts
Contact: Robert Freedman, MD (303) 315-8403 Robert.Freedman@ucdenver.edu

Locations
United States, Colorado
VA Eastern Colorado Health Care System, Denver Recruiting
Denver, Colorado, United States, 80220
Contact: Robert Freedman, MD    303-315-8403    Robert.Freedman@ucdenver.edu   
Principal Investigator: Robert Freedman, MD         
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Freedman, MD VA Eastern Colorado Health Care System, Denver
  More Information

No publications provided by Department of Veterans Affairs

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00100165     History of Changes
Other Study ID Numbers: 57710-2, VISN 19 MIRECC
Study First Received: December 23, 2004
Last Updated: April 23, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on August 28, 2014