First Episode Psychosis (FEP)
Conditions
Keywords
positron emission tomography (PET), dopamine, schizophrenia, intranasal insulin, magnetic resonance spectroscopy (MRS)
Brief summary
Patients with schizophrenia have a high risk of developing metabolic disorders and current evidence points to an overlap in mechanisms underlying psychiatric symptoms and metabolic disturbances. The main goal of this study is to investigate effects of brain insulin on dopamine signaling and energy metabolism in patients with schizophrenia experiencing their first psychotic episode (FEP). To this end, patients with schizophrenia and healthy volunteers will undergo two \[11C\]-(+)-PHNO positron emission (PET) scans to measure the changes in dopamine receptor availability after nasally applied insulin, as well as single proton magnetic resonance spectroscopy (1H-MRS) to assess the impact of intranasal insulin on levels of glucose and glutamate in the hippocampus.
Interventions
DRUGIntranasal Insulin
160 IU intranasal insulin is administered using precision air pumps twice: 15 min prior to the PET scan and 35 min prior to the 1H-MRS scan
DRUGPlacebo
Insulin-free dilution buffer is administered using precision air pumps 15 min prior to the PET scan
DRUGLow dose insulin infusion
2.5 mU/kg insulin in 100 ml isotonic saline is infused intravenously over 15min prior to PET scan when placebo is administered intranasally
DRUGPlacebo infusion
100 ml saline is infused intravenously over 15min prior to PET scan when insulin is administered intranasally
Each participant undergoes a 90-min \[11C\]-(+)-PHNO scan twice
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
All participants * age 18-40 * Body mass index (BMI) range 18-25 * good general health according to physical examination and medical history * absence of relevant abnormalities in laboratory screening, electrocardiogram (ECG) or vital signs * no regular use of drugs of abuse or alcohol based on history and urine drug screen Patients only * diagnosis of schizophrenia or schizophreniform disorder according to DSM-5 * ability to give informed consent * minimum Positive and Negative Syndrome Scale (PANSS) score of 55 with \>3 on at least two or \>4 on one PANSS psychosis item
Exclusion criteria
All participants * severe or unstable medical or neurological illness or clinically significant abnormality on screening laboratory studies or ECG * established diagnosis of type 1 or type 2 diabetes * current substance use disorder or regular recreational drug abuse (except nicotine and caffeine) * pregnancy or breastfeeding * history of head trauma resulting in loss of consciousness of \>1min or requiring medical attention * presence of MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| [11C]-(+)-PHNO BPND values | Assessed on two separate study visits within 5-12 days (scan duration: 90 min) | Dopamine D2/3 receptor availability after intranasal insulin or placebo administration |
| Hippocampal glucose and glutamate concentrations | Assessed during a single study visit (scan duration: 40 min in total) | Hippocampal glucose and glutamate concentrations before and after intranasal insulin administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in blood-based parameters of energy metabolism | Assessed at baseline and at 15min intervals after instranasal insulin/placebo administration over a period of up to 90min | Changes in concentrations of selected metabolic parameters (blood glucose, insulin, c-peptide, total cholesterol, HDL, LDL, trigycerides, ketone bodies) following intranasal insulin/placebo administration, assessed by venous blood sampling |
| Hippocampal volumetric parameters | Assessed during a single study visit, at baseline (scan duration: 10min) | Whole hippocampus and hippocampal subfield volumes assessed with structural MRI |
Countries
Austria
Contacts
Primary ContactMatthaeus Willeit
Backup ContactIrena Dajic
Outcome results
None listed