The Sub-Sero Study
Schizophrenia, Psychosis
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Pimavanserin, serotonin 2AR, MR, PET
Eligibility Criteria
Patients - Inclusion Criteria:
- Antipsychotic-free (as defined under Exclusion Criteria below)
- Fulfilling the diagnostic criteria of schizophrenia, persistent delusional disorder, acute and transient psychotic disorders, schizoaffective disorder, other non-organic psychotic disorders and unspecified non-organic disorders (ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29); verified by The Schedules for Clinical Assessment in Neuropsychiatry (SCAN) 2.0 interview (Wing et al. 1990)
- Age: 18-45 years
- Legally competent (In Danish: 'myndige og habile i retslig forstand')
Patients - Exclusion Criteria:
- Prior use of antipsychotic medication longer than an episode of two weeks in the previous year and/or 6 weeks lifetime, and/or antipsychotic treatment within 30 days prior to inclusion.
- Current substance abuse ICD-10 (F1x.2) or substance abuse in any period up to 3 months prior to referral (exception: tobacco/nicotine, F17.2)
- Head injury with more than 5 minutes of unconsciousness
- Any coercive measure
- Metal implanted by operation
- Pacemaker
- Pregnancy (assessed by urine human chorionic gonadotropin (HCG))
- Female patients: Unwillingness to use safe contraception (Intra Uterine Device/System or hormonal contraceptives) during the study period including the wash out period.
- Severe physical illness
- Known QT prolongation or congenital prolongation of the QT interval
- Medical history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia
- Current treatment with drugs known to prolong QT interval including: Class 1A antiarrhythmics (e.g., quinidine, procainamide); Class 3 antiarrhythmics (e.g., amiodarone, sotalol); certain antibiotics (e.g., gatifloxacin, moxifloxacin).
- Allergies to any of the inactive ingredients and film coat components: pregelatinized starch, magnesium stearate, microcrystalline cellulose, hypromellose, talc, titanium dioxide, polyethylene glycol, and saccharin sodium.
Healthy controls - Inclusion Criteria:
- Matched with patients on age (+/- 2 years), sex and parental socioeconomic status
- Age 18-45 years
- Legally competent (In Danish: 'myndige og habile i retslig forstand')
- Recruitment: through online advertisement (www.forsøgsperson.dk)
Healthy controls - Exclusion Criteria:
- Any psychiatric illness any first-degree relatives with known psychiatric diagnoses or physical disease
- Substance abuse during the past 3 months or positive urine-screening of illegal drugs
- Head injury with more than 5 minutes of unconsciousness
- Components of metal implanted by operation
- Pacemaker
- Pregnancy (assessed by urine HCG)
- Severe physical illness
Sites / Locations
Arms of the Study
Arm 1
Experimental
Patients
40 antipsychotic-free, first-episode schizophrenia spectrum patients will receive 6 weeks of treatment with a selective serotonin 2A Receptor (2AR) blockade. Before initiation of treatment patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR binding potential using the radioligand [¹¹C]Cimbi-36; magnetic resonance spectroscopy (MRS) of cerebral glutamate levels; structural Magnetic Resonance Imaging (MRI), including diffusion tensor imaging (DTI); cognitive and psychopathological examinations; Electrocardiography (ECG), and blood sampling for genetic- and metabolic analyses. (Full description will be updated on approval).