Dopamine and Insulin in Psychosis (DIPS)

Dopamine and Insulin in Psychosis: Imaging the Effects of Intranasal Insulin on Dopamine Transmission

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.

Study Overview

• Status: Not yet recruiting
• Conditions: First Episode Psychosis (FEP)
• Intervention / Treatment: Drug: Intranasal Insulin; Drug: Placebo; Drug: Low dose insulin infusion; Drug: Placebo infusion; Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO)

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthaeus Willeit; Phone Number: 35470 +43 1 40400; Email: matthaeus.willeit@meduniwien.ac.at
• Study Contact Backup: Name: Irena Dajic; Phone Number: 35470 +43 1 40400; Email: irena.dajic@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna
    • Contact: Matthaeus Willeit; Phone Number: 35470 +43 1 40400; Email: matthaeus.willeit@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Drug: Placebo; Insulin-free dilution buffer is administered using precision air pumps 15 min prior to the PET scan; 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; Drug: Placebo infusion; 100 ml saline is infused intravenously over 15min prior to PET scan when insulin is administered intranasally; Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO); Each participant undergoes a 90-min [11C]-(+)-PHNO scan twice
Experimental: 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	Drug: 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; Drug: Placebo; Insulin-free dilution buffer is administered using precision air pumps 15 min prior to the PET scan; 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; Drug: Placebo infusion; 100 ml saline is infused intravenously over 15min prior to PET scan when insulin is administered intranasally; Radiation: [11C] (+)-4-propyl-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO); Each participant undergoes a 90-min [11C]-(+)-PHNO scan twice
Other: Test-retest group; 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); Each participant undergoes a 90-min [11C]-(+)-PHNO scan twice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood-based parameters of energy metabolism	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	Assessed at baseline and at 15min intervals after instranasal insulin/placebo administration over a period of up to 90min
Hippocampal volumetric parameters	Whole hippocampus and hippocampal subfield volumes assessed with structural MRI	Assessed during a single study visit, at baseline (scan duration: 10min)

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: September 30, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: schizophrenia; positron emission tomography (PET); dopamine; magnetic resonance spectroscopy (MRS); intranasal insulin
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia
• Other Study ID Numbers: KLP4656125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No