Do Antipsychotic Agents Induce Supersensitivity in Humans: A Combined PET/MRI Study in Patients With Schizophrenia

ConditionSchizophrenia
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorCentral Institute of Mental Health, Mannheim

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Single PET/MR-measurement

    Radiation

    A single PET/MR-measurement using \[18F\]Fallypride with a duration of 180min. Within this measurement, the dopamine receptor agonist apomorphine is applicated.

Treatment groups

140 Participants
are divided into 3 treatment groups
Group A: Healthy subjectsOther 1 intervention
Group B: First-episode, drug-naive patients with schizophreniaExperimental treatment 1 intervention
Group C: Pretreated chronically ill patients with schizophreniaExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
160 minutes

Secondary outcomes

1

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.

Time frame
160 minutes
2

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.

Time frame
160 minutes
3

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.

Time frame
two years

Other outcomes

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