SchizophreniaNCT03911726
Do Antipsychotic Agents Induce Supersensitivity in Humans: A Combined PET/MRI Study in Patients With Schizophrenia
A study testing Single PET/MR-measurement in people with Schizophrenia, run by Central Institute of Mental Health, Mannheim at 1 site in Germany.
Trial summary
The aim of the present study is to detect changes in the dopamine system in the brain of patients with schizophrenia, especially when pretreated with antipsychotic medication. Here, the investigators want to find out whether the treatment with these drugs can cause permanent changes in docking points (receptors) of… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Single PET/MR-measurement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteGermany
- Study dates
- 1 Aug 2020to Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age: 18-65
- The subject is capable to understand scope and individual consequences of the clinical study.
- An informed consent is signed and personally dated by the subject. • No psychiatric disorder (DSM-5) currently, or in the medical history (ensured by a standardized psychiatric interview Mini International Neuropsychiatric Interview (M.I.N.I.)).
- Age: 18-65
- The criteria for schizophrenia after DSM-5 are met.
- The subject is capable to understand scope and individual consequences of the clinical study.
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- For first-episode patients, no application of antipsychotic drugs in history. Other psychoactive substances (in particular antidepressants) are allowed if last application is at least three months ago and total Duration did not exceed three months. Benzodiazepines are allowed.
- For medically pretreated patients: at least one year pharmacotherapy with one of the following three substances: aripiprazole or quetiapine or risperidone. A medication break of - depending on the plasma level - two days (quetiapine) up to two weeks (aripiprazole) should be clinically defensible.
- An informed consent is signed and personally dated by the patient. For patients with legal support in addition: signature of the legal supervisor.
Who cannot join
- Hypersensitivity against apomorphine or a chemically similar substance or one of the components of the applied medication.
- Participation in other clinical trials during or within six months prior to this clinical study.
- Medical or psychological conditions which may endanger a proper performance of the clinical trial.
- Physical disorders which interfere according to type and severity with the planned examinations, which could influence the parameter to be investigated or could compromise the subject during the examination procedure.
- Inability to comply with the study protocol.
- Limited or completely repealed legal capacity.
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- For female participants: positive pregnancy test on the day of the study inclusion or on the day of the PET/MR-measurement.
- Acute suicidality or endangerment
- Poor general condition.
- Participation in a study using ionising Radiation within the last five years.
- Alcohol abuse, alcohol dependence or addiction disease / abuse of dependence-inducing substances (excluding nicotine) in the history, additional exclusion criterion for healthy subjects: regular medication intake; within the last two weeks before PET/MR-measurement no drugs at all must be taken.
- Additional exclusion criterion for patients: other than the approved axis I diagnosis according to DSM-5. An axis II diagnosis is not a criterion for exclusion
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Central Institute of Mental Health
Mannheim, Baden-Wurttemberg, 68159
Gerhard Gründer, Prof. Dr., +49621 1703-1900, gerhard.gruender@zi-mannheim.de
Christian Schmitz, +49621 1703-2411, Christian.Schmitz@zi-mannheim.de
About this study
The aim of the present study is to detect changes in the dopamine system in the brain of patients with schizophrenia, especially when pretreated with antipsychotic medication. Here, the investigators want to find out whether the treatment with these drugs can cause permanent changes in docking points (receptors) of dopamine in the brain. It will be examined whether number and response of dopamine receptors is altered, which are associated with the onset of psychotic symptoms. For this purpose, a single PET/MR measurement will be performed in all participants. In total 140 volunteers, consisting of 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will be included over a time period of three years. In addition, the influence of nicotine consumption on dopamine receptors will be invesitgated by comparing data from smoking and non-smoking patients. In clinical practice, an elevation of dopamine action caused by alterations in receptors in the brain is of most importance. This may be the reason why the treatment with antipsychotic agents does not work in some patients. In addition, a permanent elevation of dopamine action is associated with permanent brain alterations by these drugs. The result can contribute to work out valuable indications, whether it makes sense to continue a long term therapy with antipsychotic drugs in a patient. But also the in-depth understanding of the impact of nicotine on the course of therapy can help to open up possibilities for improved drug treatment.
Read the detailed description
This project will study for the first time in humans, whether long-term treatment with antipsychotic agents, representing nowadays gold standard for patients with schizophrenia, may lead to an up regulation of dopamine D2-like receptors and associated, a supersensitivity of these receptors. The detection of such changes and the study of influencing factors (in particular smoking and type of medication) are most important for the understanding of relapse risks, development of treatment resistance and the risks for motor complications of antipsychotic pharmacotherapy. This monocentric, controlled study will include 140 participants over a time period of three years. 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will undergo a single PET/MR measurement.
- Conditions
- Schizophrenia
- Being tested
- Single PET/MR-measurement
- Keywords
- PET/MR, Dopaminergic supersensitivity, D2/3 receptor availability
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single PET/MR-measurementRadiation
A single PET/MR-measurement using [18F]Fallypride with a duration of 180min. Within this measurement, the dopamine receptor agonist apomorphine is applicated.
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects | Other | 30 healthy subjects will undergo a single PET/MR-measurement. Receives: Radiation: Single PET/MR-measurement |
| First-episode, drug-naive patients with schizophrenia | Experimental | 20 first-episode, drug-naive patients with schizophrenia will undergo a single PET/MR-measurement. Receives: Radiation: Single PET/MR-measurement |
| Pretreated chronically ill patients with schizophrenia | Experimental | 90 pretreated chronically ill patients with schizophrenia will undergo a single PET/MR-measurement. Receives: Radiation: Single PET/MR-measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dopamine D2/D3-receptor availability
Dopamine D2/D3-receptor availability measured as binding potential (BP) using PET and blood-oxygen-level-dependant (BOLD)-response measured with fMRI.
Measured: 160 minutes
Secondary outcomes (3)
D2/D3-receptor availability in first-episode, drug-naive patients with schizophrenia
In first-episode, drug-naive patients with schizophrenia expressions of NSS and AIMS correlate significantly with striatal D2/D3-receptor availability.
Measured: 160 minutes
D2/D3-receptor availability in patients with TD
In pretreated, chronically ill patients with schizophrenia, patients with TD show a significantly higher D2/D3-receptor availability than patients without TD.
Measured: 160 minutes
Follow-up of pretreated, chronically ill patients with schizophrenia
In pretreated, chronically ill patients with schizophrenia, the D2/D3-receptor availability correlates with the relapse risk and the risk for the development of TD over the course of two years.
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2019
- Study start1 Aug 2020
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (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.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All study participants will undergo a single PET/MR-measurement.
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Institute of Mental Health, Mannheim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gerhard Gründer, Prof. Dr., Principal investigator, Central Institute of Mental Health, Mannheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03911726
- Sponsor's protocol ID
- 2018-09-18
- Status last verified
- Sep 2026
- First submitted
- 9 Apr 2019
- Last updated
- 8 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Antipsychotic Agents Induce Supersensitivity in Humans: A Combined PET/MRI Study in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT03911726
- Acronym / sponsor ID
- 2018-09-18
- Conditions
- Schizophrenia
- Keywords
- PET/MR, Dopaminergic supersensitivity, D2/3 receptor availability
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Central Institute of Mental Health, MannheimUniversity, hospital or other
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 11 Apr 2019 (actual)
- 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 aim of the present study is to detect changes in the dopamine system in the brain of patients with schizophrenia, especially when pretreated with antipsychotic medication. Here, the investigators want to find out whether the treatment with these drugs can cause permanent changes in docking points (receptors) of dopamine in the brain. It will be examined whether number and response of dopamine receptors is altered, which are associated with the onset of psychotic symptoms. For this purpose, a single PET/MR measurement will be performed in all participants. In total 140 volunteers, consisting of 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will be included over a time period of three years. In addition, the influence of nicotine consumption on dopamine receptors will be invesitgated by comparing data from smoking and non-smoking patients. In clinical practice, an elevation of dopamine action caused by alterations in receptors in the brain is of most importance. This may be the reason why the treatment with antipsychotic agents does not work in some patients. In addition, a permanent elevation of dopamine action is associated with permanent brain alterations by these drugs. The result can contribute to work out valuable indications, whether it makes sense to continue a long term therapy with antipsychotic drugs in a patient. But also the in-depth understanding of the impact of nicotine on the course of therapy can help to open up possibilities for improved drug treatment.
Detailed description
This project will study for the first time in humans, whether long-term treatment with antipsychotic agents, representing nowadays gold standard for patients with schizophrenia, may lead to an up regulation of dopamine D2-like receptors and associated, a supersensitivity of these receptors. The detection of such changes and the study of influencing factors (in particular smoking and type of medication) are most important for the understanding of relapse risks, development of treatment resistance and the risks for motor complications of antipsychotic pharmacotherapy. This monocentric, controlled study will include 140 participants over a time period of three years. 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will undergo a single PET/MR measurement.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- All study participants will undergo a single PET/MR-measurement.
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects | Other | Radiation: Single PET/MR-measurement30 healthy subjects will undergo a single PET/MR-measurement. |
| First-episode, drug-naive patients with schizophrenia | Experimental | Radiation: Single PET/MR-measurement20 first-episode, drug-naive patients with schizophrenia will undergo a single PET/MR-measurement. |
| Pretreated chronically ill patients with schizophrenia | Experimental | Radiation: Single PET/MR-measurement90 pretreated chronically ill patients with schizophrenia will undergo a single PET/MR-measurement. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age: 18-65
- The subject is capable to understand scope and individual consequences of the clinical study.
- An informed consent is signed and personally dated by the subject. • No psychiatric disorder (DSM-5) currently, or in the medical history (ensured by a standardized psychiatric interview Mini International Neuropsychiatric Interview (M.I.N.I.)).
- Age: 18-65
- The criteria for schizophrenia after DSM-5 are met.
Key exclusion criteria (12 listed)
- Hypersensitivity against apomorphine or a chemically similar substance or one of the components of the applied medication.
- Participation in other clinical trials during or within six months prior to this clinical study.
- Medical or psychological conditions which may endanger a proper performance of the clinical trial.
- Physical disorders which interfere according to type and severity with the planned examinations, which could influence the parameter to be investigated or could compromise the subject during the examination procedure.
- Inability to comply with the study protocol.
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 |
|---|---|---|
| Single PET/MR-measurementA single PET/MR-measurement using [18F]Fallypride with a duration of 180min. Within this measurement, the dopamine receptor agonist apomorphine is applicated. | Radiation | First-episode, drug-naive patients with schizophrenia, Healthy subjects, Pretreated chronically ill patients with schizophrenia |
Primary outcome
Dopamine D2/D3-receptor availability
Time frame: 160 minutes
Dopamine D2/D3-receptor availability measured as binding potential (BP) using PET and blood-oxygen-level-dependant (BOLD)-response measured with fMRI.
3 secondary outcomes
D2/D3-receptor availability in first-episode, drug-naive patients with schizophrenia
Time frame: 160 minutes
D2/D3-receptor availability in patients with TD
Time frame: 160 minutes
Follow-up of pretreated, chronically ill patients with schizophrenia
Time frame: two years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
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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.
Gerhard Gründer, Prof. Dr. principal investigator
Central Institute of Mental Health, Mannheim
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single PET/MR-measurement in people with Schizophrenia, run by Central Institute of Mental Health, Mannheim at 1 site in Germany.
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 9 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gerhard Gründer, Prof. Dr. (+49621 1703-1900, gerhard.gruender@zi-mannheim.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dopamine D2/D3-receptor availability (time frame: 160 minutes). 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 8 Sep 2026.