KetoBrain: Brain Energy Metabolism in Schizophrenia

NCT07309172 | Recruiting

• 1 other identifier: 2025_KetoBrain
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Objective The objective is to recruit antipsychotic-naïve patients at the first diagnosis with a first-episode schizophrenia disorder (FES) to study ketone metabolism of the brain via PET neuroimaging. Participants will undergo PET neuroimaging at baseline before start of antipsychotic treatment and after 4-8 weeks of antipsychotic treatment including an additional clinical follow-up visit after 6 months. In addition, a healthy control group with one baseline visit will be recruited. Study design Non-interventional neuroimaging study with pre-defined follow-up visits. Patients Patients with a FES (ICD-10: F20) aged 18-35 years who are antipsychotic-naïve including age- and sex-matched healthy controls. Sample size This is an observational pilot project. Currently, no studies have measured brain ketone metabolism before and after AP intake. Assuming a 50% dropout rate at follow-up, the investigators aim to recruit 22 patients to obtain 12 full datasets - a sample size commonly used in PET studies. Healthy controls will only have one study day, so no dropouts are expected - aiming at a sample size of 12 healthy controls. Procedures Patients will be included at the first FES diagnosis. Before inclusion, an interview with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview will validate the diagnosis. At baseline and follow-up (details in the full protocol and Table 1), patients will be rated by use of the 6-item Positive and Negative Syndrome Scale (PANSS-6), the Clinical Global Impression Severity Scale (CGI-S), the Global Assessment of Functioning Scale (GAF), Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), Fagerström Test for Nicotine Dependence (FTND), and the Calgary Depression Scale for Schizophrenia (CDSS). The Matrics Consensus Cognitive Battery (MCCB), which consists of 10 cognitive tests, will measure cognition. Heart rate, blood pressure, height, body weight, waist and hip circumference will be recorded. Patients will be treated according to clinical indication, i.e., they will receive routine clinical care at the local psychiatric hospital and participation in this study will not affect the treatment. Follow-up Patients will be treated and followed according to normal clinical treatment guidelines at the local psychiatric hospitals, which will not be affected by participation. A re-scan will be performed after 4-8 weeks of antipsychotic treatment. Endpoints The primary endpoints are

1. 1.Brain ketone and glucose metabolism in FES before antipsychotic treatment compared to healthy controls measured via PET
2. 2.Brain ketone and glucose metabolism in FES after antipsychotic treatment

Conditions

Schizophrenia Disorder

Keywords

Schizophrenia; PET neuroimaging; Brain energy substrate metabolism; Ketone bodies; Glucose

Outcome Measures

Primary Outcomes (2)

• Whole brain ketone and glucose metabolism in FES compared to healthy controls measured via PET

  At enrollment, i.e. at the baseline PET scan

• Whole brain ketone and glucose metabolism in FES after antipsychotic treatment

  From baseline scan to the follow-up scan after 4-8 weeks of antipsychotic treatment

Secondary Outcomes (2)

• Correlation between antipsychotic response, as measured on the PANSS-6, with the change in brain ketone and glucose metabolism in patients with FES

  From baseline to follow-up scan after 4-8 weeks of antipsychotic treatment

• Correlation between the MCCB with the change in brain ketone and glucose metabolism in patients with FES

  From baseline to follow-up scan after 4-8 weeks of antipsychotic treatment

Study Arms (2)

Patients with first-episode schizophrenia

Healthy controls

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Antipsychotic-naive patients with FES and healthy controls

You may qualify if:

• Age 18-35 years
• Diagnosed with FES (ICD-10: F20)
• Able to give informed oral and written consent.
• Age 18-35 years
• No mental disorder (ICD-10: F00-99)
• Able to give informed oral and written consent.

You may not qualify if:

• Any coercive measure including patients in forensic psychiatry
• In a clinical condition where the treating clinician evaluates that the patient is not able to attend the research study.
• Previous use of AP at an antipsychotic dose (except for Risperidone ≤0.5 mg, Abilify ≤2.5 mg, Seroquel ≤50 mg or Zyprexa ≤2.5 mg) for more than 2 continuous weeks in the past year and/or 6 weeks over a lifetime
• Seroquel/Quetiapine 50 mg 4.2 Risperdal/Risperidone 0.5 mg
• Comorbidity: Borderline intelligence or intellectual disability, autism spectrum disorder, decompensated substance use disorder, psychosis induced by a medical condition or psychosis induced by medication or drug use.
• Pregnancy, childbirth within the past 6 months, or breastfeeding. Female participants should use an effective contraception.
• Contraindications to MRI (metal, severe claustrophobia).
• Acute suicidal thoughts (e.g., resulting in hospitalization)
• Diabetes mellitus type 1. History of severe head trauma, stroke, chemotherapy or brain surgery. Hypo- or hyperthyroidism. Epilepsy. Systemic glucocorticoid hormone treatment.
• Other conditions interfering with participation according to the qualified physician's judgment.
• Previous use of an antipsychotic dose (except for Risperidone ≤0.5 mg, Abilify ≤2.5 mg, Seroquel ≤50 mg or Zyprexa ≤2.5 mg) for more than 2 continuous weeks in the past year and/or 6 weeks over a lifetime
• Seroquel/Quetiapine 50 mg
• Risperdal/Risperidone 0.5 mg
• Pregnancy, childbirth within the past 6 months, or breastfeeding. Female participants should use an effective contraception.
• Contraindications to MRI (metal, severe claustrophobia).

Sponsors & Collaborators

• Ole Köhler-Forsberg: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Aarhus University Hospital, Psychosis Research Unit

Aarhus, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

A blood sample will be stored at -80 C to measure ketone bodies. After this, the blood samples will be destroyed.

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Central Study Contacts

Ole Köhler-Forsberg, MD, PhD, DMSc

CONTACT

004578471610; karkoe@rm.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Assoc. Professor

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 30, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)