Investigation of the Drug Dimethoxbenzylidene Anabaseine in Treating Schizophrenia Patients

Study Overview
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Brief Summary
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This study will determine the effectiveness of a drug, dimethoxbenzylidene anabaseine, in producing beneficial effects similar to that of nicotine in individuals with schizophrenia.

Detailed Description
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Schizophrenia is a chronic and severe brain disorder that can significantly impact quality of life. It is characterized by delusions, paranoia, and disordered thinking. The cause of schizophrenia has not yet been determined. However, there are many treatments, including drug therapy and cognitive behavioral therapy, that may help to alleviate symptoms of the condition. Nicotinic receptors are involved in a number of biological processes; they are numerous throughout the central and peripheral nervous systems and are diverse in structure and expression. Genetic and neurobiological research has identified decreased expression of the a7 nicotinic receptor as an element in schizophrenia that is related to poor psychosocial outcome. Data indicate that drug therapy may reduce this deficit in receptor expression. Nicotine has been found to stimulate the a7 nicotinic receptor; however, the physiological dependence associated with nicotine makes it an undesirable option. Dimethoxbenzylidene anabaseine (DMXB-A) can stimulate the a7 nicotinic receptor; its advantages include easy oral administration and the lack of dependence-causing effects. This study will determine whether DMXB-A can safely and effectively stimulate the a7 nicotinic receptor in schizophrenia patients and reduce their neurobiological symptoms. This study will last 6 weeks. Participants will have study visits each week for the duration of the study. During each visit, participants will be randomly assigned to receive either DMXB-A or placebo. An electrocardiogram (EKG) will measure the heart function of participants and participants' blood pressure will be measured. After the first dose of either DMXB-A or placebo, participants will receive a second dose 2 hours later. An evoked potential test, which measures the brain's response to stimuli, will be performed after both doses. Neuropsychological tests, such as verbal reasoning and visual retention, will be performed following the second dose of either DMXB-A or placebo.

Official Title
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Phase 1 Trial of 3-2,4 Dimethoxbenzylidene Anabaseine in Schizophrenia

Conditions
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Schizophrenia, Psychotic Disorders

Intervention / Treatment
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* Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
* Drug: Placebo
* Drug: Dimethoxybenzylidene anabaseine (DMXB-A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia Exclusion Criteria: History of cardiovascular illness or neurological illness other than schizophrenia Current substance abuse, including nicotine History of clozapine use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimethoxybenzylidene anabaseine 75 mg<br>Participants will take active experimental medication (Dimethoxybenzylidene anabaseine (DMXB-A) 75 mg) | Drug: Dimethoxybenzylidene anabaseine (DMXB-A)<br>* DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose<br>Drug: Placebo<br>* Placebo dosed to match active medication<br>Drug: Dimethoxybenzylidene anabaseine (DMXB-A)<br>* DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose<br>|
| Placebo Comparator: Placebo<br>Participants will take placebo. | Drug: Dimethoxybenzylidene anabaseine (DMXB-A)<br>* DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose<br>Drug: Placebo<br>* Placebo dosed to match active medication<br>Drug: Dimethoxybenzylidene anabaseine (DMXB-A)<br>* DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose<br>|
| Experimental: Dimethoxybenzylidene anabaseine 150 mg<br>Participants will take active experimental medication (Dimethoxybenzylidene anabaseine (DMXB-A) 150 mg) | Drug: Dimethoxybenzylidene anabaseine (DMXB-A)<br>* DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose<br>Drug: Placebo<br>* Placebo dosed to match active medication<br>Drug: Dimethoxybenzylidene anabaseine (DMXB-A)<br>* DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Scale Score for the Repeatable Battery for the Assessment of Neuropsychological Status | ten subtests which give five scores, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, delayed memory). | Measured at 2 hours after drug or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Psychiatric Rating Scale | Brief Psychiatric Rating Scale (BPRS) is a rating scale used to measure psychiatric symptoms | Measured 4 hours after drug or placebo administration | 
| P50 auditory evoked potential test amplitude/conditioning amplitude ratio | The evoked response amplitude measured in mV to the initial auditory stimulus which is compared to the evoked response amplitude which is measured in mV to a second auditory stimulus that occurs 500 ms later. | Measured 2.5 hours after drug or placebo administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Evoked Potentials, 3-(2,4-dimethoxybenzylidene)anabaseine, DMXB-A, Receptors, Nicotinic