NCT03911726

Brief 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 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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
140

participants targeted

Target at P75+ for not_applicable schizophrenia

Timeline
Completed

Started Aug 2020

Longer than P75 for not_applicable schizophrenia

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 9, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 11, 2019

Completed
1.3 years until next milestone

Study Start

First participant enrolled

August 1, 2020

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2025

Completed
Last Updated

April 8, 2025

Status Verified

April 1, 2025

Enrollment Period

5.4 years

First QC Date

April 9, 2019

Last Update Submit

April 3, 2025

Conditions

Schizophrenia

Keywords

PET/MRDopaminergic supersensitivityD2/3 receptor availability

Outcome Measures

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.

    160 minutes

Secondary Outcomes (3)

  • D2/D3-receptor availability in first-episode, drug-naive patients with schizophrenia

    160 minutes

  • D2/D3-receptor availability in patients with TD

    160 minutes

  • Follow-up of pretreated, chronically ill patients with schizophrenia

    two years

Study Arms (3)

Healthy subjects

OTHER

30 healthy subjects will undergo a single PET/MR-measurement.

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.

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.

Radiation: Single PET/MR-measurement

Interventions

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.

First-episode, drug-naive patients with schizophreniaHealthy subjectsPretreated chronically ill patients with schizophrenia

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.
  • Acute suicidality or endangerment
  • Poor general condition.
  • Participation in a study using ionising Radiation within the last five years.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Central Institute of Mental Health

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Study Officials

  • Gerhard Gründer, Prof. Dr.

    Central Institute of Mental Health, Mannheim

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: All study participants will undergo a single PET/MR-measurement.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 9, 2019

First Posted

April 11, 2019

Study Start

August 1, 2020

Primary Completion

December 31, 2025

Study Completion

December 31, 2025

Last Updated

April 8, 2025

Record last verified: 2025-04

Locations

DE(1)