SchizophreniaDPTPNCT02880995
[18 Fluorine(F)]DOPA Determinants and Predictors of Treatment Response in Psychosis
A study testing PET scan, clinical scale and 6 weeks of treatment with amisulpride in people with Schizophrenia, run by Seoul National University Hospital at 2 sites in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- PET scan, clinical scale and 6 weeks of treatment with amisulpride
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 1 Nov 2017to Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- 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
Who cannot join
- Participants should not have any neurological illness such as head trauma, seizure and meningitis.
- Participants should not be diagnosed as Mental retardation(IQ<70)
- Participants should not have severe personality disorder, substance abuse or dependence (except for nicotine abuse and dependence) and severe medical conditions.
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites
Seoul National University Bundang Hospital
Seongnam, 13620
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 463-707
About this study
Official title: Positron Emission Tomography(PET) With 3,4-dihydroxy-6-18-fluoro-l-phenylalanine ([18 Fluorine(F)]DOPA) Determinants and Predictors of Treatment Response in Psychosis
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.
Read the 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:
- 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
- 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
- Being tested
- PET scan, clinical scale, 6 weeks of treatment with amisulpride
- Keywords
- dopamine receptor occupancy, antipsychotics, positron emission tomography
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET scanDevice
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 scaleBehavioural
Patient group should complete clinical scales at baseline and 6 week.
6 weeks of treatment with amisulprideDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| patient group | Experimental | * 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. Receives: Device: PET scan; Behavioral: clinical scale; Drug: 6 weeks of treatment with amisulpride |
| healthy control group | Other | * 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 Receives: Device: PET scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: the difference of Ki(cer) between healthy controls and patient group at the baseline
Secondary outcomes (3)
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.
Measured: change from baseline Positive and Negative Syndrome Scale and at 6 wk
Age
The investigators should check up participants' age
Measured: at baseline
Sex
The investigators should check up participants' sex
Measured: at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2016 (estimated)
- Study start1 Nov 2017
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Euitae Kim, Seoul National University Hospital
- Investigators
- Euitae Kim, Ph. D., Study chair, Seoul National University Bundang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02880995
- Sponsor's protocol ID
- DOPAPET_predictor-1000
- Acronym
- DPTP
- Status last verified
- Sep 2019
- First submitted
- 4 Aug 2016
- Last updated
- 25 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positron Emission Tomography(PET) With 3,4-dihydroxy-6-18-fluoro-l-phenylalanine ([18 Fluorine(F)]DOPA) Determinants and Predictors of Treatment Response in Psychosis
- ClinicalTrials.gov ID
- NCT02880995
- Acronym / sponsor ID
- DPTP / DOPAPET_predictor-1000
- Conditions
- Schizophrenia
- Keywords
- dopamine receptor occupancy, antipsychotics, positron emission tomography
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 26 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patient group | Experimental | Device: PET scan, Behavioral: clinical scale, Drug: 6 weeks of treatment with amisulpride* 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. |
| healthy control group | Other | Device: PET scan* 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 |
Who may qualify
- Ages
- 19 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
- 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
Key exclusion criteria (3 listed)
- Participants should not have any neurological illness such as head trauma, seizure and meningitis.
- Participants should not be diagnosed as Mental retardation(IQ<70)
- Participants should not have severe personality disorder, substance abuse or dependence (except for nicotine abuse and dependence) and severe medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET scanThe 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. | Device | healthy control group, patient group |
| clinical scalePatient group should complete clinical scales at baseline and 6 week. | Behavioural | patient group |
| 6 weeks of treatment with amisulprideAlso: amisulprideThe 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. | Drug | patient group |
Primary outcome
the difference of Ki(cer) of [18 fluorine(F)]DOPA PET
Time frame: the difference of Ki(cer) between healthy controls and patient group at the baseline
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.
3 secondary outcomes
clinical scale(Positive and Negative Syndrome Scale)
Time frame: change from baseline Positive and Negative Syndrome Scale and at 6 wk
Age
Time frame: at baseline
Sex
Time frame: at baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Euitae Kim, Ph. D. study chair
Seoul National University Bundang Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET scan, clinical scale and 6 weeks of treatment with amisulpride in people with Schizophrenia, run by Seoul National University Hospital at 2 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the difference of Ki(cer) of [18 fluorine(F)]DOPA PET (time frame: the difference of Ki(cer) between healthy controls and patient group at the baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.