Dopamine and Insulin in Psychosis (DIPS)

Medical University of Vienna

Status: Not yet enrolling

Conditions: First Episode Psychosis (FEP)

Treatments: Drug: Placebo; Drug: Low dose insulin infusion; Drug: Placebo infusion; Drug: Intranasal Insulin; Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

Study type: Interventional

Funder types: Other

Identifiers

NCT07252752

KLP4656125

Details and patient eligibility

About

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.

Enrollment: 46 estimated patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

46 participants in 3 patient groups

Schizophrenia group

Experimental group

Description:

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

Treatment:

Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

Drug: Intranasal Insulin

Drug: Placebo infusion

Drug: Low dose insulin infusion

Drug: Placebo

Healthy volunteer group

Experimental group

Description:

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

Treatment:

Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

Drug: Intranasal Insulin

Drug: Placebo infusion

Drug: Low dose insulin infusion

Drug: Placebo

Test-retest group

Other group

Description:

6 healthy volunteers will undergo (i) two \[11C\]-(+)-PHNO PET scans, and (ii) 1H-MRS for test-retest purposes

Treatment:

Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)