Dopamine and Insulin in Psychosis

NCT ID: NCT07252752

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2029-01-01

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.

Conditions

First Episode Psychosis (FEP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Intranasal Insulin

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Insulin-free dilution buffer is administered using precision air pumps 15 min prior to the PET scan

Low dose insulin infusion

Intervention Type: DRUG

2.5 mU/kg insulin in 100 ml isotonic saline is infused intravenously over 15min prior to PET scan when placebo is administered intranasally

Placebo infusion

Intervention Type: DRUG

100 ml saline is infused intravenously over 15min prior to PET scan when insulin is administered intranasally

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

Intervention Type: RADIATION

Each participant undergoes a 90-min \[11C\]-(+)-PHNO scan twice

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

Group Type: EXPERIMENTAL

Intranasal Insulin

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Insulin-free dilution buffer is administered using precision air pumps 15 min prior to the PET scan

Low dose insulin infusion

Intervention Type: DRUG

2.5 mU/kg insulin in 100 ml isotonic saline is infused intravenously over 15min prior to PET scan when placebo is administered intranasally

Placebo infusion

Intervention Type: DRUG

100 ml saline is infused intravenously over 15min prior to PET scan when insulin is administered intranasally

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

Intervention Type: RADIATION

Each participant undergoes a 90-min \[11C\]-(+)-PHNO scan twice

Test-retest group

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

Group Type: OTHER

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

Intervention Type: RADIATION

Each participant undergoes a 90-min \[11C\]-(+)-PHNO scan twice

Interventions

Intranasal 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

Intervention Type: DRUG

Placebo

Insulin-free dilution buffer is administered using precision air pumps 15 min prior to the PET scan

Intervention Type: DRUG

Low 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

Intervention Type: DRUG

Placebo infusion

100 ml saline is infused intravenously over 15min prior to PET scan when insulin is administered intranasally

Intervention Type: DRUG

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

Each participant undergoes a 90-min \[11C\]-(+)-PHNO scan twice

Intervention Type: RADIATION

Eligibility Criteria

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Matthäus Willeit

Ao. Univ. Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of Vienna

Vienna, , Austria

Countries

Austria

Central Contacts

Matthaeus Willeit

Role: CONTACT

matthaeus.willeit@meduniwien.ac.at

+43 1 40400 ext. 35470

Irena Dajic

Role: CONTACT

irena.dajic@meduniwien.ac.at

+43 1 40400 ext. 35470

Facility Contacts

Matthaeus Willeit

Role: primary

matthaeus.willeit@meduniwien.ac.at

+43 1 40400 ext. 35470

Other Identifiers

KLP4656125

Identifier Type: -

Identifier Source: org_study_id