Dopamine and Insulin in Psychosis: Imaging the Effects of Intranasal Insulin on Dopamine Transmission
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- [11C]-(+)-PHNO BPND values
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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 exclusion criteria
- •if participation in this study would exceed annual radiation dose limits (30mSv)
- •clinically established diagnosis of intellectual disability
- •Healthy volunteers only
- •Psychiatric disorder according to Mini-International Neuropsychiatric Interview (M.I.N.I.)
- •Schizophrenia or bipolar disorder in first degree family members
- •Patients only
- •● Previous oral antipsychotic treatment for more than 2 weeks or previous treatment with antipsychotic depot preparation
研究组 & 干预措施
Schizophrenia group
20 antipsychotic-naive patients with first episode psychosis will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Intranasal Insulin (Drug)
Schizophrenia group
20 antipsychotic-naive patients with first episode psychosis will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Placebo (Drug)
Schizophrenia group
20 antipsychotic-naive patients with first episode psychosis will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Low dose insulin infusion (Drug)
Schizophrenia group
20 antipsychotic-naive patients with first episode psychosis will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Placebo infusion (Drug)
Schizophrenia group
20 antipsychotic-naive patients with first episode psychosis will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) (Radiation)
Healthy volunteer group
20 healthy volunteers will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Intranasal Insulin (Drug)
Healthy volunteer group
20 healthy volunteers will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Placebo (Drug)
Healthy volunteer group
20 healthy volunteers will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Low dose insulin infusion (Drug)
Healthy volunteer group
20 healthy volunteers will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: Placebo infusion (Drug)
Healthy volunteer group
20 healthy volunteers will undergo (i) two [11C]-(+)-PHNO PET scans preceded by intranasal insulin or placebo administration in a randomized counterbalanced order, and (ii) 1H-MRS before and after intranasal insulin
干预措施: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) (Radiation)
Test-retest group
6 healthy volunteers will undergo (i) two [11C]-(+)-PHNO PET scans, and (ii) 1H-MRS for test-retest purposes
干预措施: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) (Radiation)
结局指标
主要结局
[11C]-(+)-PHNO BPND values
时间窗: 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
时间窗: Assessed during a single study visit (scan duration: 40 min in total)
Hippocampal glucose and glutamate concentrations before and after intranasal insulin administration
次要结局
- 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)
- Hippocampal volumetric parameters(Assessed during a single study visit, at baseline (scan duration: 10min))
研究者
Matthäus Willeit
Ao. Univ. Prof. Dr.
Medical University of Vienna