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The first purpose of this study is to determine if dopamine synthesis capacity is significantly lower in treatment non-responders from illness onset relative to treatment responders. And the second purpose of this study is to determine the potential of [18 fluorine(F)]-DOPA to be used to predict treatment response to antipsychotic treatment in first episode psychosis.
Schizophrenia is amongst the leading causes of global disability in adults. A major factor underlying this is that about 30% of patients show little or no response to first-line antipsychotic drugs. There is one drug, clozapine, with proven efficacy in these patients. However, currently there are no good predictors of treatment non-response and consequently patients have to undergo empirical trials with first-line drugs. This contributes to the long delays, on average 4-5 years, seen in identifying and starting patients on clozapine. Furthermore, clozapine is poorly tolerated and has potentially life-threatening side-effects, which mean that the investigators desperately need new, alternative drugs. Lack of understanding of the neurobiological basis underlying non-response has impeded the development of alternatives to clozapine in the past. However recently it has been shown that non-responders show reduced dopamine synthesis capacity relative to patients who have responded to antipsychotics. The effect size for this difference is very large, d>1.2. This study was cross-sectional, in patients who had already received antipsychotic treatment for a number of years. The key questions now are thus:
To test this the investigators are going to investigate the relationship between presynaptic dopamine dysfunction and antipsychotic responsiveness in a prospective study.
For this, the investigators are going to measure striatal dopamine synthesis capacity using [18 fluorine(F)]DOPA positron emission tomography in drug-naïve first episode psychosis and determine treatment response after 6 weeks of treatment with amisulpride. Response will be defined as a >30% reduction in symptom ratings on the Positive and Negative Syndrome Scale.
The effect size in our cross-sectional study was d=1.3. Based on this effect size a sample size of 12 per group will have >80% power to detect a group difference with p<0.05 2-tailed using an independent t-test. Given a non-response rate of 30% the investigators will thus require 40 patients at baseline to get 12 non-responders. To allow for 20% drop-outs we will require 50 patients at baseline.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| patient group | Experimental |
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| healthy control group | Other |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PET scan | Device | The patient group and the healthy control group will undergo PET scan at the baseline. the investigators are going to measure striatal dopamine synthesis capacity using [18 fluorine(F)]DOPA positron emission tomography in drug-naïve first episode psychosis and determine treatment response after 6 weeks of treatment with amisulpride. Response will be defined as a >30% reduction in symptom ratings on the Positive and Negative Syndrome Scale. |
| Measure | Description | Time Frame |
|---|---|---|
| the difference of Ki(cer) of [18 fluorine(F)]DOPA PET | Subjects in the patient group will receive a intake of antipsychotics(amisulpride) for the six-week period and they will also undergo PET imaging at the baseline. After six-week marks, the investigators will determine treatment responders and nonresponders. And the investigators will detect the correlation between the capacity of presynaptic dopamine, treatment response and nonresponse in the patients. | the difference of Ki(cer) between healthy controls and patient group at the baseline |
| Measure | Description | Time Frame |
|---|---|---|
| clinical scale(Positive and Negative Syndrome Scale) | The investigators are going to measure striatal dopamine synthesis capacity using [18 fluorine(F)]DOPA positron emission tomography in drug-naïve first episode psychosis and determine treatment response after 6 weeks of treatment with amisulpride. Response will be defined as a >30% reduction in symptom ratings on the Positive and Negative Syndrome Scale. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Euitae Kim, Ph. D. | Seoul National University Bundang Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Bundang Hospital | Seongnam-si | Gyeonggi-do | 463-707 | South Korea | ||
| Seoul National University Bundang Hospital |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D049268 | Positron-Emission Tomography |
| D000073216 | Mental Status and Dementia Tests |
| D013812 | Therapeutics |
| D000077582 | Amisulpride |
| ID | Term |
|---|---|
| D014055 | Tomography, Emission-Computed |
| D007090 | Image Interpretation, Computer-Assisted |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
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|
| clinical scale | Behavioral | Patient group should complete clinical scales at baseline and 6 week. |
|
| 6 weeks of treatment with amisulpride | Drug | The investigators are going to measure striatal dopamine synthesis capacity using [18 fluorine(F)]DOPA positron emission tomography in drug-naïve first episode psychosis and determine treatment response after 6 weeks of treatment with amisulpride. Response will be defined as a >30% reduction in symptom ratings on the Positive and Negative Syndrome Scale. |
|
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| change from baseline Positive and Negative Syndrome Scale and at 6 wk |
| Age | The investigators should check up participants' age | at baseline |
| Sex | The investigators should check up participants' sex | at baseline |
| Seongnam |
| 13620 |
| South Korea |
| D003933 | Diagnosis |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011877 | Radionuclide Imaging |
| D014054 | Tomography |
| D003947 | Diagnostic Techniques, Radioisotope |
| D009483 | Neuropsychological Tests |
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |