Dopamine and Insulin in Psychosis

NCT07252752 | Not Yet Recruiting

• 1 other identifier: KLP4656125
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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)

Keywords

positron emission tomography (PET); dopamine; schizophrenia; intranasal insulin; magnetic resonance spectroscopy (MRS)

Outcome Measures

Primary Outcomes (2)

• [11C]-(+)-PHNO BPND values

  Dopamine D2/3 receptor availability after intranasal insulin or placebo administration

  Assessed on two separate study visits within 5-12 days (scan duration: 90 min)

• Hippocampal glucose and glutamate concentrations

  Hippocampal glucose and glutamate concentrations before and after intranasal insulin administration

  Assessed during a single study visit (scan duration: 40 min in total)

Secondary Outcomes (2)

• 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)

Study Arms (3)

Schizophrenia group

EXPERIMENTAL

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

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

Healthy volunteer group

EXPERIMENTAL

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

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

Test-retest group

OTHER

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

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

Interventions

Intranasal Insulin 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

Healthy volunteer group; Schizophrenia group

Placebo DRUG

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

Healthy volunteer group; Schizophrenia group

Low dose insulin infusion 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

Healthy volunteer group; Schizophrenia group

Placebo infusion DRUG

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

Healthy volunteer group; Schizophrenia group

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

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

Healthy volunteer group; Schizophrenia group; Test-retest group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Central Study Contacts

Matthaeus Willeit

CONTACT

+43 1 40400; matthaeus.willeit@meduniwien.ac.at

Irena Dajic

CONTACT

+43 1 40400; irena.dajic@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ao. Univ. Prof. Dr.

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: November 28, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: November 28, 2025

Record last verified: 2025-11

Locations

AU (1)