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

January 27, 2020 updated by: University of Colorado, Denver

Phase 2 Trial of the Nicotinic Agonist 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80220
        • VA Eastern Colorado Health Care System, Denver, CO

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • inactive substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

VA Office of Research and Development

Investigators

  • Principal Investigator: Robert Freedman, MD, VA Eastern Colorado Health Care System, Denver, CO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

December 23, 2004

First Submitted That Met QC Criteria

December 23, 2004

First Posted (Estimate)

December 24, 2004

Study Record Updates

Last Update Posted (Actual)

January 29, 2020

Last Update Submitted That Met QC Criteria

January 27, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-0837
  • VISN 19 MIRECC (Other Grant/Funding Number: VA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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