Nicotinic Receptors and Schizophrenia

Study Overview
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Brief Summary
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The investigators hypothesize that sustained-release DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) will provide clinical improvement in cognition in patients with schizophrenia who are smokers and who are non-smokers. The study drug may also maintain abstinence from cigarette smoking and improve other symptoms in patients with schizophrenia.

Detailed Description
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Patients with schizophrenia will be screened then enrolled for one week placebo trial in addition to their existing antipsychotic medication. If pill compliance is greater than 80%, then they will receive baseline clinical, cognitive, and brain imaging and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram. Then patients will receive in a randomized double blind trial either DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) or placebo comparator in addition to their existing antipsychotic medication. After one month patients will receive repeat clinical, cognitive, and brain imaging testing and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram.

Official Title
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Nicotinic Receptors and Schizophrenia: Phase II

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: DMXB-A-SR
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be selected to be 18 to 65 years old and in good general health. Subjects who fulfill Diagnostic and Statistical Manual -IV-Text Revision (DSM-IV-TR) criteria for schizophrenia or schizoaffective disorder. Smokers will smoke at least 20 cigarettes per day. Non-smokers will also be enrolled. Subjects will have normal: vital signs, hematology, serum chemistries, EKG, and urinalysis with a negative drug screen before entry into the study. Subjects will be fluent in English. Smoking subjects will be interested in stopping smoking in the near future and not interested in nicotine replacement therapy. Exclusion Criteria: Subjects with histories of: neurological illness, liver disease, severe hypertension (cut-off blood pressure 160/100) or cardiac disease, or renal failure (cut-off creatinine above 1.4). Subjects who currently meet DSM-IV-TR criteria for substance dependence other than nicotine, cannabis, or alcohol will be excluded. Women who are capable of pregnancy and not on acceptable forms of birth control will be excluded. Subjects being treated with Clozapine will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Random allocation to a treatment and placebo group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DMXB-A-SR<br>Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR), 3-2, 4 dimethoxybenzylidene anabaseine sustained release (GTS-21) | Drug: DMXB-A-SR<br>* Experimental Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR)<br>* Other names: GTS-21;|
| Placebo Comparator: Arm #2: Placebo Comparator<br>Inert capsule to resemble active drug. | Other: Placebo<br>* Placebo Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive Efficacy | MATRICS CCB Neurocognitive T-score (Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery Statistically Adjusted-score). Higher scores indicate better neurocognitive functionality. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli | The P50 evoked response paired of auditory stimuli S1, S2, is measured. The inhibition is expressed as the ratio P50 S2 amplitude divided by P50 S1 amplitude. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Trial, Smoking, Smoking Cessation, Cognition, Mental Focus