Clinical trial NCT01555814: Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE): Substudy Site Copenhagen
Official title: Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE): the Effects of D2 Antagonism on Candidate Endophenotypes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizophreniform Disorder
Schizoaffective Disorder
Keywords: dopamine
first episode
reward
cognition
MRI
fMRI
PPI
P300
P50 gating
endophenotypes
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Glostrup University Hospital, Copenhagen
name: Rigshospitalet, Denmark
name: Institute of Psychiatry, London
name: UMC Utrecht
name: Copenhagen Hospital Corporation
First posted: 2012-03-15
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The investigators want to relate disturbances in first-episode schizophrenic patients in (dopaminergic) D2 receptors, brain structure, brain function, and information processing to each other and to psychopathology. Additionally, the investigators want to examine the influence of D2 receptor blockade on these disturbances. The investigators expect disturbances in the dopaminergic system at baseline to correlate with specific structural and functional changes and with disruption in information processing as measured with psychophysiological and neurocognitive methods - and investigators expect D2 receptor blockade to reverse some of the functional and cognitive impairments. The investigators do not expect any effect of treatment on brain structure.

Detailed description: The study is designed as a 4 week case-control follow-up study of 90 FE pt. with SCZ and 90 controls matched with regard to age, gender, and parental socio-economic status. All subjects will be examined with a diagnostic interview (SCAN, Schedule for Clinical Assessment in Neuropsychiatry), medical and family history, and physical examination before inclusion. At baseline subjects will be examined with single photon emission computed tomography (SPECT), MRI, fMRI, psychophysiology, neurocognition. In addition, they will be screened for drugs, genetic testing, and ECG. Patients will further be examined with clinical validated rating scales to measure psychopathology, subjective well-being, and side-effects. After a period of 4 weeks all assessments are repeated. During that period patients will be treated with amisulpride, while healthy controls will receive no treatment at all. Efficacy of antipsychotic treatment will be evaluated after this initial period of 4 weeks. All subjects will be re-assessed in the same test battery as mentioned above, except for SPECT and fMRI, after a period of 6, 12, and 24 months.

Eligibility criteria: Inclusion Criteria:

* Schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV)
* Age 18-40 years
* Written informed consent.

Exclusion Criteria:

* A time interval between the onset of positive symptoms (hallucinations and/or delusions) and study entry exceeding two years.
* Prior use of antipsychotic medication longer than an episode of two weeks in the previous year and/or 6 weeks lifetime.
* Intolerance to one of the drugs in this study. Patients who are coercively treated at a psychiatric ward (based on a judicial ruling)
* Patients who are represented by a legal ward or under legal custody
* The presence of one or more of the contraindications against any of the study drugs as mentioned in the SPC texts
* Pregnancy, as determined through a pregnancy test, or lactation

Primary outcomes:
measure: Relationship between specific neuropsychiatric measures and global improvement on PANSS scores
timeFrame: 4 weeks of medical treatment
Secondary outcomes:
measure: Effect of antipsychotic medication on the D2 binding potential (SPECT) in antipsychotic naive patients with schizophrenia.
timeFrame: Baseline, 4 weeks
measure: Effect of antipsychotic medication on P50-suppression
timeFrame: Baseline, 4 weeks, 6,12,24 months
measure: Effect of antipsychotic medication on the human reward system
timeFrame: Baseline and 4 weeks follow up
measure: Change in hippocampal and basal ganglia volume from baseline to follow-up.
timeFrame: 4 weeks, 6, 12 and 24 months,
measure: Change in processing speed over time after antipsychotic treatment.
timeFrame: Baseline, 4 weeks, 6,12,24 months
measure: Change in levels of brain perfusion from baseline to follow-up.
timeFrame: Baseline, 4 weeks treatment
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup Glostrup, Denmark
Study officials:
affiliation: Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup Glostrup, Denmark
name: Birte Glenthøj, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: