Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 2 Trial of a Nicotinic Agonist in Schizophrenia (DMXB-A)

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.
 
ClinicalTrials.gov Identifier: NCT00100165
Recruitment Status : Completed
First Posted : December 24, 2004
Results First Posted : January 29, 2020
Last Update Posted : January 29, 2020
Sponsor:
Collaborator:
VA Office of Research and Development
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
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 or disease Intervention/treatment Phase
Schizophrenia Drug: Placebo Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg Phase 2

Detailed Description:

The objective of the trial is to determine if dosing 3-(2,4 dimethoxybenzylidene anabaseine) 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 functional magnetic resonance imaging. The purpose of these neurobiological measures is to assess whether the response to 3-(2,4 dimethoxybenzylidene anabaseine) 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 3-(2,4 dimethoxybenzylidene anabaseine) and related compounds.

The purpose of the trial is to lay the groundwork for Phase III investigation. If this trial finds that 3-(2,4 dimethoxybenzylidene anabaseine) 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 3-(2,4 dimethoxybenzylidene anabaseine) (150 mg + 75 mg 2 hours later), 3-(2,4 dimethoxybenzylidene anabaseine)(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 3-(2,4 dimethoxybenzylidene anabaseine)(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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2 Trial of the Nicotinic Agonist 3-(2,4 Dimethoxybenzylidene Anabaseine) in Schizophrenia
Study Start Date : January 2005
Actual Primary Completion Date : July 2007
Actual Study Completion Date : July 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg
Patient receives 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg twice per day in a blinded capsule.
Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 150 mg
3-(2,4 dimethoxybenzylidene) 150 mg by mouth twice a day for 4 weeks
Other Name: GTS-21

Experimental: 3-(2,4 dimethoxybenzylidene anabaseine)75 mg
Patient receives 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg twice per day in a blinded capsule.
Drug: 3-(2,4 dimethoxybenzylidene anabaseine) 75 mg
3-(2,4 dimethoxybenzylidene) 75 mg by mouth twice a day for 4 weeks
Other Name: GTS-21

Placebo Comparator: placebo
Patient receives placebo twice per day in a blinded capsule.
Drug: Placebo
Placebo by mouth twice a day for 4 weeks
Other Name: inactive substance




Primary Outcome Measures :
  1. Neurocognitive Performance [ Time Frame: 1 month ]
    The measurement of neurocognitive performance on 6 domains, speed of processing, attention/vigilance, working memory, verbal learning, visual learning and reasoning/problem solving. Each domain is compared to a normative sample of schizophrenia subjects and the performance is determined and compared by a T-Test to the subjects baseline performance to determine the effect of drug or placebo. The scale is the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia Neurocognitive Consensus Combined Battery, range 0-100. A higher score indicates better performance.


Secondary Outcome Measures :
  1. Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: 1 month ]
    The Scale for the Assessment of Negative Symptoms measures the measure negative symptoms in schizophrenia by measuring the domains of anhedonia, alogia, avolition and anhedonia in schizophrenia on a scale from 1 to 20 that sums the global scores of all 4 domains, each of which are rated on a scale of 1-5. Higher scores indicate greater severity of negative symptoms



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00100165


Locations
Layout table for location information
United States, Colorado
VA Eastern Colorado Health Care System, Denver, CO
Denver, Colorado, United States, 80220
Sponsors and Collaborators
University of Colorado, Denver
VA Office of Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Robert Freedman, MD VA Eastern Colorado Health Care System, Denver, CO
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00100165    
Other Study ID Numbers: 08-0837
VISN 19 MIRECC ( Other Grant/Funding Number: VA )
First Posted: December 24, 2004    Key Record Dates
Results First Posted: January 29, 2020
Last Update Posted: January 29, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by University of Colorado, Denver:
Schizophrenia
Additional relevant MeSH terms:
Layout table for MeSH terms
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
3-(2,4-dimethoxybenzylidene)anabaseine
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs