Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Drug Trial, Smoking, Smoking Cessation, Cognition, Mental Focus
Brief summary
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
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.
Interventions
DRUGDMXB-A-SR
Experimental Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR)
OTHERPlacebo
Placebo Comparator
Sponsors
National Institute of Mental Health (NIMH)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The pharmacist places the treatment or placebo into identical coded vials. Only the pharmacist and the statistician have the code to identify of the treatment.
Intervention model description
Random allocation to a treatment and placebo group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Efficacy | 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli | 4 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DMXB-A-SR Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR), 3-2, 4 dimethoxybenzylidene anabaseine sustained release (GTS-21)
DMXB-A-SR: Experimental Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR) | 40 |
| Arm #2: Placebo Comparator Inert capsule to resemble active drug.
Placebo: Placebo Comparator | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | DMXB-A-SR | Total | Arm #2: Placebo Comparator |
|---|---|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 12.4 | 44.8 years STANDARD_DEVIATION 12.7 | 43.2 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 76 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 16 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 62 Participants | 30 Participants |
| Region of Enrollment United States | 40 participants | 80 participants | 40 participants |
| Sex: Female, Male Female | 8 Participants | 20 Participants | 12 Participants |
| Sex: Female, Male Male | 32 Participants | 60 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
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.
Time frame: 4 weeks
Population: participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DMXB-A-SR | Neurocognitive Efficacy | 0.6 MATRICS Neurocognitive T score | Standard Deviation 5.8 |
| Arm #2: Placebo Comparator | Neurocognitive Efficacy | 2.1 MATRICS Neurocognitive T score | Standard Deviation 8.2 |
p-value: 0.89ANOVA
Secondary
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.
Time frame: 4 weeks
Population: Participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DMXB-A-SR | Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli | 0.57 percentage of amplitude | Standard Deviation 0.12 |
| Arm #2: Placebo Comparator | Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli | 0.52 percentage of amplitude | Standard Deviation 0.14 |