Phase 2 Trial of a Nicotinic Agonist in Schizophrenia (DMXB-A)
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|ClinicalTrials.gov Identifier: NCT00100165|
Recruitment Status : Completed
First Posted : December 24, 2004
Results First Posted : January 29, 2020
Last Update Posted : January 29, 2020
|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|
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 (Clinical Trial)|
|Actual Enrollment :||29 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|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|
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.
Placebo by mouth twice a day for 4 weeks
Other Name: inactive substance
- 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.
- 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
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
|United States, Colorado|
|VA Eastern Colorado Health Care System, Denver, CO|
|Denver, Colorado, United States, 80220|
|Principal Investigator:||Robert Freedman, MD||VA Eastern Colorado Health Care System, Denver, CO|