[18 Fluorine(F)]DOPA Determinants and Predictors of Treatment Response in Psychosis

NCT ID: NCT02880995

Last Updated: 2019-09-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-01
• Study Completion Date: 2019-12-31

Brief Summary

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.

Detailed Description

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:

1. is dopamine synthesis capacity different at illness onset in drug naïve patients who subsequently show non-response to antipsychotic treatment relative to drug naïve patients who respond to treatment

2. is it possible to predict who will respond to treatment

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

patient group

• 50 Drug-naïve patients with first episode psychosis (We anticipate the non-responder rate will be 30% of the patients)

1. Drug-naïve

2. Diagnosed as first episode psychosis

3. The total score of PANSS>70

4. No co-morbid psychiatric illness (including drug dependence/abuse)

• They will also undergo PET scan at the baseline. And the investigators are going to determine treatment response after 6 weeks of treatment with amisulpride. Also they should complete clinical scales at 0, 2, 4, 6, and 8 week.

Group Type: EXPERIMENTAL

PET scan

Intervention Type: 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.

clinical scale

Intervention Type: BEHAVIORAL

Patient group should complete clinical scales at baseline and 6 week.

6 weeks of treatment with amisulpride

Intervention Type: 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.

healthy control group

• 12 healthy volunteers

1. No history of psychiatric disorder (including drug dependence/abuse)

2. No history of physical illness

3. No contra-indication to scanning

• They will also undergo PET scan at the baseline

Group Type: OTHER

PET scan

Intervention Type: 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.

Interventions

PET scan

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.

Intervention Type: DEVICE

clinical scale

Patient group should complete clinical scales at baseline and 6 week.

Intervention Type: BEHAVIORAL

6 weeks of treatment with amisulpride

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.

Intervention Type: DRUG

Other Intervention Names

amisulpride

Eligibility Criteria

Inclusion Criteria

1. Patient group (1) Patients who met Diagnostic and Statistical Manual of Mental Disorders(DSM)-IV criteria for schizophrenia, schizoaffective disorder, and schizophreniform disorder (2) Patients diagnosed with first episode psychosis which occurred within 2 years and not having been treated with antipsychotics(Drug-naïve) (3) The total score of PANSS>70

2. Healthy control group (1) Healthy controls has no Axis I disorder and do not report any past event of neurological or psychiatric illness assessed by the Structured Clinical Interview for DSM Disorders (2) No history of physical illness (3) No contra-indication to scanning

Exclusion Criteria

1. Participants should not have any neurological illness such as head trauma, seizure and meningitis.

2. Participants should not be diagnosed as Mental retardation(IQ<70)

3. Participants should not have severe personality disorder, substance abuse or dependence (except for nicotine abuse and dependence) and severe medical conditions.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Euitae Kim

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Euitae Kim, Ph. D.

Role: STUDY_CHAIR

Seoul National University Bundang Hospital

Locations

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Countries

South Korea

Other Identifiers

DOPAPET_predictor-1000

Identifier Type: -

Identifier Source: org_study_id